Signal (IPC)

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Signal_(IPC)

Signals are standardized messages sent to a running program to trigger specific behavior, such as quitting or error handling. They are a limited form of inter-process communication (IPC), typically used in Unix, Unix-like, and other POSIX-compliant operating systems.

A signal is an asynchronous notification sent to a process or to a specific thread within the same process to notify it of an event. Common uses of signals are to interrupt, suspend, terminate or kill a process. Signals originated in 1970s Bell Labs Unix and were later specified in the POSIX standard.

When a signal is sent, the operating system interrupts the target process' normal flow of execution to deliver the signal. Execution can be interrupted during any non-atomic instruction. If the process has previously registered a signal handler, that routine is executed. Otherwise, the default signal handler is executed.

Embedded programs may find signals useful for inter-process communications, as signals are notable for their Algorithmic efficiency.

Signals are similar to interrupts, the difference being that interrupts are mediated by the CPU and handled by the kernel while signals are mediated by the kernel (possibly via system calls) and handled by individual processes. The kernel may pass an interrupt as a signal to the process that caused it (typical examples are SIGSEGV, SIGBUS, SIGILL and SIGFPE).

History

• Version 1 Unix (1971) had separate system calls to catch interrupts, quits, and machine traps.
• kill appeared in Version 2 (1972).
• Version 4 (1973) combined all traps into one call, signal.
• Version 5 (1974) could send arbitrary signals.
• In Version 7 (1979) each numbered trap received a symbolic name.
• Plan 9 from Bell Labs (mid 80s) replaced signals with notes, which permit sending short, arbitrary strings.

Sending signals

The kill(2) system call sends a specified signal to a specified process, if permissions allow. Similarly, the kill(1) command allows a user to send signals to processes. The raise(3) library function sends the specified signal to the current process.

Exceptions such as division by zero, segmentation violation (SIGSEGV), and floating point exception (SIGFPE) will cause a core dump and terminate the program.

The kernel can generate signals to notify processes of events. For example, SIGPIPE will be generated when a process writes to a pipe which has been closed by the reader; by default, this causes the process to terminate, which is convenient when constructing shell pipelines.

Typing certain key combinations at the controlling terminal of a running process causes the system to send it certain signals:

• Ctrl-C (in older Unixes, DEL) sends an INT signal ("interrupt", SIGINT); by default, this causes the process to terminate.
• Ctrl-Z sends a TSTP signal ("terminal stop", SIGTSTP); by default, this causes the process to suspend execution.
• Ctrl-\ sends a QUIT signal (SIGQUIT); by default, this causes the process to terminate and dump core.
• Ctrl-T (not supported on all UNIXes) sends an INFO signal (SIGINFO); by default, and if supported by the command, this causes the operating system to show information about the running command.

These default key combinations with modern operating systems can be changed with the stty command.

Handling signals

Signal handlers can be installed with the signal(2) or sigaction(2) system call. If a signal handler is not installed for a particular signal, the default handler is used. Otherwise the signal is intercepted and the signal handler is invoked. The process can also specify two default behaviors, without creating a handler: ignore the signal (SIG_IGN) and use the default signal handler (SIG_DFL). There are two signals which cannot be intercepted and handled: SIGKILL and SIGSTOP.

Risks

Signal handling is vulnerable to race conditions. As signals are asynchronous, another signal (even of the same type) can be delivered to the process during execution of the signal handling routine.

The sigprocmask(2) call can be used to block and unblock delivery of signals. Blocked signals are not delivered to the process until unblocked. Signals that cannot be ignored (SIGKILL and SIGSTOP) cannot be blocked.

Signals can cause the interruption of a system call in progress, leaving it to the application to manage a non-transparent restart.

Signal handlers should be written in a way that does not result in any unwanted side-effects, e.g. errno alteration, signal mask alteration, signal disposition change, and other global process attribute changes. Use of non-reentrant functions, e.g., malloc or printf, inside signal handlers is also unsafe. In particular, the POSIX specification and the Linux man page signal (7) require that all system functions directly or indirectly called from a signal function are async-signal safe. The signal-safety(7) man page gives a list of such async-signal safe system functions (practically the system calls), otherwise it is an undefined behavior. It is suggested to simply set some volatile sig_atomic_t variable in a signal handler, and to test it elsewhere.

Signal handlers can instead put the signal into a queue and immediately return. The main thread will then continue "uninterrupted" until signals are taken from the queue, such as in an event loop. "Uninterrupted" here means that operations that block may return prematurely and must be resumed, as mentioned above. Signals should be processed from the queue on the main thread and not by worker pools, as that reintroduces the problem of asynchronicity. However, managing a queue is not possible in an async-signal safe way with only sig_atomic_t, as only single reads and writes to such variables are guaranteed to be atomic, not increments or (fetch-and)-decrements, as would be required for a queue. Thus, effectively, only one signal per handler can be queued safely with sig_atomic_t until it has been processed.

Relationship with hardware exceptions

A process's execution may result in the generation of a hardware exception, for instance, if the process attempts to divide by zero or incurs a page fault.

In Unix-like operating systems, this event automatically changes the processor context to start executing a kernel exception handler. In case of some exceptions, such as a page fault, the kernel has sufficient information to fully handle the event itself and resume the process's execution.

Other exceptions, however, the kernel cannot process intelligently and it must instead defer the exception handling operation to the faulting process. This deferral is achieved via the signal mechanism, wherein the kernel sends to the process a signal corresponding to the current exception. For example, if a process attempted integer divide by zero on an x86 CPU, a divide error exception would be generated and cause the kernel to send the SIGFPE signal to the process.

Similarly, if the process attempted to access a memory address outside of its virtual address space, the kernel would notify the process of this violation via a SIGSEGV (segmentation violation signal). The exact mapping between signal names and exceptions is obviously dependent upon the CPU, since exception types differ between architectures.

POSIX signals

The list below documents the signals specified in the Single Unix Specification. All signals are defined as macro constants in the <signal.h> header file. The name of the macro constant consists of a "SIG" prefix followed by a mnemonic name for the signal.

SIGABRT and SIGIOT

"Signal abort", "signal input/output trap"

The SIGABRT signal is sent to a process to tell it to abort, i.e. to terminate. The signal is usually initiated by the process itself when it calls abort() function of the C Standard Library, but it can be sent to the process from outside like any other signal.

SIGIOT indicates that the CPU has executed an explicit "trap" instruction (without a defined function), or an unimplemented instruction (when emulation is unavailable).

Note: "input/output trap" is a misnomer for any CPU "trap" instruction. The term reflects early usage of such instructions, predominantly to implement I/O functions, but they are not inherently tied to device I/O and may be used for other purposes such as communication between virtual & real hosts.

SIGIOT and SIGABRT are typically the same signal, and receipt of that signal may indicate any of the conditions above.

SIGALRM, SIGVTALRM and SIGPROF

"Signal alarm", "signal virtual timer alarm", "signal profiling timer alarm"

The SIGALRM, SIGVTALRM and SIGPROF signals are sent to a process when the corresponding time limit is reached. The process sets these time limits by calling alarm or setitimer. The time limit for SIGALRM is based on real or clock time; SIGVTALRM is based on CPU time used by the process; and SIGPROF is based on CPU time used by the process and by the system on its behalf (known as a profiling timer). On some systems SIGALRM may be used internally by the implementation of the sleep function.

SIGBUS

"Signal bus"

The SIGBUS signal is sent to a process when it causes a bus error. The conditions that lead to the signal being sent are, for example, incorrect memory access alignment or non-existent physical address.

SIGCHLD

"Signal child"

The SIGCHLD signal is sent to a process when a child process terminates, is stopped, or resumes after being stopped. One common usage of the signal is to instruct the operating system to clean up the resources used by a child process after its termination without an explicit call to the wait system call.

SIGCONT

"Signal continue"

The SIGCONT signal instructs the operating system to continue (restart) a process previously paused by the SIGSTOP or SIGTSTP signal. One important use of this signal is in job control in the Unix shell.

SIGFPE

"Signal floating-point error"

The SIGFPE signal is sent to a process when an exceptional (but not necessarily erroneous) condition has been detected in the floating point or integer arithmetic hardware. This may include division by zero, floating point underflow or overflow, integer overflow, an invalid operation or an inexact computation. Behaviour may differ depending on hardware.

SIGHUP

"Signal hangup"

The SIGHUP signal is sent to a process when its controlling terminal is closed. It was originally designed to notify the process of a serial line drop (a hangup). In modern systems, this signal usually means that the controlling pseudo or virtual terminal has been closed. Many daemons (who have no controlling terminal) interpret receipt of this signal as a request to reload their configuration files and flush/reopen their logfiles instead of exiting. nohup is a command to make a command ignore the signal.

SIGILL

"Signal illegal"

The SIGILL signal is sent to a process when it attempts to execute an illegal, malformed, unknown, or privileged instruction.

SIGINT

"Signal interrupt"

The SIGINT signal is sent to a process by its controlling terminal when a user wishes to interrupt the process. This is typically initiated by pressing Ctrl+C, but on some systems, the "delete" character or "break" key can be used.

SIGKILL

"Signal kill"

The SIGKILL signal is sent to a process to cause it to terminate immediately (kill). In contrast to SIGTERM and SIGINT, this signal cannot be caught or ignored, and the receiving process cannot perform any clean-up upon receiving this signal. The following exceptions apply:

• Zombie processes cannot be killed since they are already dead and waiting for their parent processes to reap them.
• Processes that are in the blocked state will not die until they wake up again.
• The init process is special: It does not get signals that it does not want to handle, and thus it can ignore SIGKILL. An exception from this rule is while init is ptraced on Linux.
• An uninterruptibly sleeping process may not terminate (and free its resources) even when sent SIGKILL. This is one of the few cases in which a UNIX system may have to be rebooted to solve a temporary software problem.

SIGKILL is used as a last resort when terminating processes in most system shutdown procedures if it does not voluntarily exit in response to SIGTERM. To speed the computer shutdown procedure, Mac OS X 10.6, aka Snow Leopard, will send SIGKILL to applications that have marked themselves "clean" resulting in faster shutdown times with, presumably, no ill effects. The command killall -9 has a similar, while dangerous effect, when executed e.g. in Linux; it does not let programs save unsaved data. It has other options, and with none, uses the safer SIGTERM signal.

SIGPIPE

"Signal pipe"

The SIGPIPE signal is sent to a process when it attempts to write to a pipe without a process connected to the other end.

SIGPOLL

"Signal poll"

The SIGPOLL signal is sent when an event occurred on an explicitly watched file descriptor. Using it effectively leads to making asynchronous I/O requests since the kernel will poll the descriptor in place of the caller. It provides an alternative to active polling.

SIGRTMIN to SIGRTMAX

"Signal real-time minimum", "signal real-time maximum"

The SIGRTMIN to SIGRTMAX signals are intended to be used for user-defined purposes. They are real-time signals.

SIGQUIT

"Signal quit"

The SIGQUIT signal is sent to a process by its controlling terminal when the user requests that the process quit and perform a core dump.

SIGSEGV

"Signal segmentation violation"

The SIGSEGV signal is sent to a process when it makes an invalid virtual memory reference, or segmentation fault, i.e. when it performs a segmentation violation.

SIGSTOP

"Signal stop"

The SIGSTOP signal instructs the operating system to stop a process for later resumption.

SIGSYS

"Signal system call"

The SIGSYS signal is sent to a process when it passes a bad argument to a system call. In practice, this kind of signal is rarely encountered since applications rely on libraries (e.g. libc) to make the call for them. SIGSYS can be received by applications violating the Linux Seccomp security rules configured to restrict them. SIGSYS can also be used to emulate foreign system calls, e.g. emulate Windows system calls on Linux.

SIGTERM

"Signal terminate"

The SIGTERM signal is sent to a process to request its termination. Unlike the SIGKILL signal, it can be caught and interpreted or ignored by the process. This allows the process to perform nice termination releasing resources and saving state if appropriate. SIGINT is nearly identical to SIGTERM.

SIGTSTP

"Signal terminal stop"

The SIGTSTP signal is sent to a process by its controlling terminal to request it to stop (terminal stop). It is commonly initiated by the user pressing Ctrl+Z. Unlike SIGSTOP, the process can register a signal handler for, or ignore, the signal.

SIGTTIN and SIGTTOU

The SIGTTIN and SIGTTOU signals are sent to a process when it attempts to read in or write out respectively from the tty while in the background. Typically, these signals are received only by processes under job control; daemons do not have controlling terminals and, therefore, should never receive these signals.

SIGTRAP

"Signal trap"

The SIGTRAP signal is sent to a process when an exception (or trap) occurs: a condition that a debugger has requested to be informed of – for example, when a particular function is executed, or when a particular variable changes value.

SIGURG

"Signal urgent"

The SIGURG signal is sent to a process when a socket has urgent or out-of-band data available to read.

SIGUSR1 and SIGUSR2

"Signal user 1", "signal user 2""

The SIGUSR1 and SIGUSR2 signals are sent to a process to indicate user-defined conditions.

SIGXCPU

"Signal exceeded CPU"

The SIGXCPU signal is sent to a process when it has used up the CPU for a duration that exceeds a certain predetermined user-settable value. The arrival of a SIGXCPU signal provides the receiving process a chance to quickly save any intermediate results and to exit gracefully, before it is terminated by the operating system using the SIGKILL signal.

SIGXFSZ

"Signal excess file size"

The SIGXFSZ signal is sent to a process when it grows a file that exceeds the maximum allowed size.

SIGWINCH

"Signal window change"

The SIGWINCH signal is sent to a process when its controlling terminal changes its size (a window change).

Default action

A process can define how to handle incoming POSIX signals. If a process does not define a behaviour for a signal, then the default handler for that signal is being used. The table below lists some default actions for POSIX-compliant UNIX systems, such as FreeBSD, OpenBSD and Linux.

Signal	Portable number	Default action	Description
SIGABRT	6	Terminate (core dump)	Process abort signal
SIGALRM	14	Terminate	Alarm clock
SIGBUS	—	Terminate (core dump)	Access to an undefined portion of a memory object
SIGCHLD	—	Ignore	Child process terminated, stopped, or continued
SIGCONT	—	Continue	Continue executing, if stopped
SIGFPE	8	Terminate (core dump)	Erroneous arithmetic operation
SIGHUP	1	Terminate	Hangup
SIGILL	4	Terminate (core dump)	Illegal instruction
SIGINT	2	Terminate	Terminal interrupt signal
SIGKILL	9	Terminate	Kill (cannot be caught or ignored)
SIGPIPE	13	Terminate	Write on a pipe with no one to read it
SIGPOLL	—	Terminate	Pollable event
SIGPROF	—	Terminate	Profiling timer expired
SIGQUIT	3	Terminate (core dump)	Terminal quit signal
SIGSEGV	11	Terminate (core dump)	Invalid memory reference
SIGSTOP	—	Stop	Stop executing (cannot be caught or ignored)
SIGSYS	—	Terminate (core dump)	Bad system call
SIGTERM	15	Terminate	Termination signal
SIGTRAP	5	Terminate (core dump)	Trace/breakpoint trap
SIGTSTP	—	Stop	Terminal stop signal
SIGTTIN	—	Stop	Background process attempting read
SIGTTOU	—	Stop	Background process attempting write
SIGUSR1	—	Terminate	User-defined signal 1
SIGUSR2	—	Terminate	User-defined signal 2
SIGURG	—	Ignore	Out-of-band data is available at a socket
SIGVTALRM	—	Terminate	Virtual timer expired
SIGXCPU	—	Terminate (core dump)	CPU time limit exceeded
SIGXFSZ	—	Terminate (core dump)	File size limit exceeded
SIGWINCH	—	Ignore	Terminal window size changed

Portable number:

For most signals the corresponding signal number is implementation-defined. This column lists the numbers specified in the POSIX standard.

Actions explained:

Terminate – Abnormal termination of the process. The process is terminated with all the consequences of _exit() except that the status made available to wait() and waitpid() indicates abnormal termination by the specified signal.

Terminate (core dump) – Abnormal termination of the process. Additionally, implementation-defined abnormal termination actions, such as creation of a core file, may occur.

Ignore – Ignore the signal.

Stop – Stop (or suspend) the process.

Continue – Continue the process, if it is stopped; otherwise, ignore the signal.

Miscellaneous signals

The following signals are not specified in the POSIX specification. They are, however, sometimes used on various systems.

SIGEMT

The SIGEMT signal is sent to a process when an emulator trap occurs.

SIGINFO

The SIGINFO signal is sent to a process when a status (info) request is received from the controlling terminal.

SIGPWR

The SIGPWR signal is sent to a process when the system experiences a power failure.

SIGLOST

The SIGLOST signal is sent to a process when a file lock is lost.

SIGSTKFLT

The SIGSTKFLT signal is sent to a process when the coprocessor experiences a stack fault (i.e. popping when the stack is empty or pushing when it is full). It is defined by, but not used on Linux, where a x87 coprocessor stack fault will generate SIGFPE instead.

SIGUNUSED

The SIGUNUSED signal is sent to a process when a system call with an unused system call number is made. It is synonymous with SIGSYS on most architectures.

SIGCLD

The SIGCLD signal is synonymous with SIGCHLD.

Cancer treatment

From Wikipedia, the free encyclopedia

https://en.wikipedia.org/wiki/Cancer_treatment 

 

Cancer treatment
A patient prepared for radiation therapy
Specialty	Oncology
ICD-10-PCS	110000053

Cancer treatments are a wide range of treatments available for the many different types of cancer, with each cancer type needing its own specific treatment. Treatments can include surgery, chemotherapy, radiation therapy, hormonal therapy, targeted therapy including small-molecule drugs or monoclonal antibodies, and PARP inhibitors such as olaparib . Other therapies include hyperthermia, immunotherapy, photodynamic therapy, and stem-cell therapy. Most commonly cancer treatment involves a series of separate therapies such as chemotherapy before surgery. Angiogenesis inhibitors are sometimes used to enhance the effects of immunotherapies.

The choice of therapy depends upon the location and grade of the tumor and the stage of the disease, as well as the general state of the patient. Biomarker testing can help to determine the type of cancer, and indicate the best therapy. A number of experimental cancer treatments are continuously under development. In 2023 it was estimated that one in five people will be diagnosed with cancer at some point in their lifetime.

The primary goal of cancer treatment is to either cure the cancer by its complete removal, or to considerably prolong the life of the individual. Palliative care is involved when the prognosis is poor and the cancer termed as terminal. There are many types of cancer, and many of these can be successfully treated if detected early enough.

Types of treatments

The treatment of cancer has undergone evolutionary changes as understanding of the underlying biological processes has increased. Tumor removal surgeries have been documented in ancient Egypt, hormone therapy and radiation therapy were developed in the late 19th century. Chemotherapy, immunotherapy and newer targeted therapies are products of the 20th century. As new information about the biology of cancer emerges, treatments will be developed and modified to increase effectiveness, precision, survivability, and quality of life.

Surgery

Malignant tumours can be cured if entirely removed by surgery. But if the cancer has already spread (metastasized) to other sites, complete surgical excision is usually impossible. In the Halstedian model of cancer progression, tumors grow locally, then spread to the lymph nodes, then to the rest of the body. This has given rise to the popularity of local-only treatments such as surgery for small cancers. Even small localized tumors are increasingly recognized as possessing metastatic potential.

Examples of surgical procedures for cancer include mastectomy, and lumpectomy for breast cancer, prostatectomy for prostate cancer, and lung cancer surgery for non-small cell lung cancer. The goal of the surgery can be either the removal of only the tumor, the entire organ, or part of the organ. A single cancer cell is invisible to the naked eye but can regrow into a new tumor, a process called recurrence. For this reason, the pathologist will examine the surgical specimen to determine if a margin of healthy tissue is present, thus decreasing the chance that microscopic cancer cells are left in the patient.

In addition to removal of the primary tumor, surgery is often necessary for staging, e.g. determining the extent of the disease and whether it has metastasized to regional lymph nodes. Staging is a major determinant of prognosis and of the need for adjuvant therapy. Occasionally, surgery is necessary to control symptoms, such as spinal cord compression or bowel obstruction. This is referred to as palliative treatment.

Surgery may be performed before or after other forms of treatment. Treatment before surgery is often described as neoadjuvant. In breast cancer, the survival rate of patients who receive neoadjuvant chemotherapy are no different from those who are treated following surgery. Giving chemotherapy earlier allows oncologists to evaluate the effectiveness of the therapy, and may make removal of the tumor easier. However, the survival advantages of neoadjuvant treatment in lung cancer are less clear.

Radiation therapy

Main article: Radiation therapy

See also: Radiosurgery

Radiation therapy (radiotherapy) is the use of ionizing radiation to kill cancer cells and shrink tumors by damaging their DNA causing cellular death. Radiation therapy can either damage DNA directly or create charged particles (free radicals) within the cells that can in turn damage the DNA. Radiation therapy can be administered externally via external beam radiotherapy or internally via brachytherapy. The effects of radiation therapy are localised and confined to the region being treated. Although radiation damages both cancer cells and normal cells, most normal cells can recover from the effects of radiation and function properly. The goal of radiation therapy is to damage as many cancer cells as possible, while limiting harm to nearby healthy tissue. Hence, it is given in many fractions, allowing healthy tissue to recover between fractions.

Radiation therapy may be used to treat almost every type of solid tumor, and may also be used to treat leukemia and lymphoma. Radiation dose to each site depends on a number of factors, including the radio sensitivity of each cancer type and whether there are tissues and organs nearby that may be damaged by radiation. Thus, as with every form of treatment, radiation therapy is not without its side effects.

Radiation therapy can lead to dry mouth from exposure of salivary glands to radiation, resulting in decreased saliva secretion. Post therapy, the salivary glands will resume functioning but rarely in the same fashion. Dry mouth caused by radiation can be a permanent problem. Radiation might not be a choice of treatment if the tumor was diagnosed in late stages or is in a vulnerable location, as radiation might be more likely to cause damage to organs at effective doses. Moreover, radiation therapy for patients under 14 can cause particularly significant long-term side effects, such as hearing loss and blindness, that influence the lifestyle of the young patients. Children who had received cranial radiotherapy are deemed at a high risk for academic failure and cognitive delay.

Chemotherapy

Main article: Chemotherapy

Chemotherapy is the treatment of cancer with drugs ("anticancer drugs") that can destroy cancer cells. Chemotherapy can be given in a variety of ways such as injections into the muscles, skin, artery, or vein, or it could even be taken by mouth in the form of a pill. In current usage, the term "chemotherapy" usually refers to cytotoxic drugs which affect rapidly dividing cells in general, in contrast with targeted therapy (see below). Chemotherapy drugs interfere with cell division in various possible ways, e.g. with the duplication of DNA or the separation of newly formed chromosomes. Most forms of chemotherapy target all rapidly dividing cells and are not specific to cancer cells, although some degree of specificity may come from the inability of many cancer cells to repair DNA damage, while normal cells generally can. Hence, chemotherapy has the potential to harm healthy tissue, especially those tissues that have a high replacement rate (e.g. intestinal lining). These cells usually repair themselves after chemotherapy.

Because some drugs work better together than alone, two or more drugs are often given at the same time. This is called "combination chemotherapy"; most chemotherapy regimens are given in a combination.

Since chemotherapy affects the whole body, it can have a wide range of side effects. Patients often find that they start losing their hair since the drugs that are combatting the cancer cells also attack the cells in the hair roots. This powerful treatment can also lead to fatigue, loss of appetite, and vomiting depending on the person.

The treatment of some leukaemias and lymphomas requires the use of high-dose chemotherapy, and total body irradiation (TBI). This treatment ablates the bone marrow, and hence the body's ability to recover and repopulate the blood. For this reason, bone marrow, or peripheral blood stem cell harvesting is carried out before the ablative part of the therapy, to enable "rescue" after the treatment has been given. This is known as autologous stem cell transplantation.

Targeted therapies

Main article: Targeted therapy

Targeted therapy, which first became available in the late 1990s, has had a significant impact in the treatment of some types of cancer, and is currently a very active research area. This constitutes the use of agents specific for the deregulated proteins of cancer cells. Small molecule drugs are targeted therapy drugs that are generally inhibitors of enzymatic domains on mutated, overexpressed, or otherwise critical proteins within the cancer cell. Prominent examples are the tyrosine kinase inhibitors imatinib (Gleevec/Glivec) and gefitinib (Iressa).

Monoclonal antibody therapy is another strategy in which the therapeutic agent is an antibody which specifically binds to a protein on the surface of the cancer cells. Examples include the anti-HER2/neu antibody trastuzumab (Herceptin) used in breast cancer, and the anti-CD20 antibody rituximab, used in a variety of B-cell malignancies.

Targeted therapy can also involve small peptides as "homing devices" which can bind to cell surface receptors or affected extracellular matrix surrounding the tumor. Radionuclides which are attached to these peptides (e.g. RGDs) eventually kill the cancer cell if the nuclide decays in the vicinity of the cell. Especially oligo- or multimers of these binding motifs are of great interest, since this can lead to enhanced tumor specificity and avidity.

Photodynamic therapy (PDT) is a ternary treatment for cancer involving a photosensitizer, tissue oxygen, and light (often using lasers). PDT can be used as treatment for basal cell carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of large tumors. In February 2019, medical scientists announced that iridium attached to albumin, creating a photosensitized molecule, can penetrate cancer cells and, after being irradiated with light, destroy the cancer cells.

High-energy therapeutic ultrasound could increase higher-density anti-cancer drug load and nanomedicines to target tumor sites by 20x fold higher than traditional target cancer therapy.

Targeted therapies under pre-clinical development as potential cancer treatments include morpholino splice switching oligonucleotides, which induce ERG exon skipping in prostate cancer models, multitargeted kinase inhibitors that inhibit the PI3K with other pathways including MEK and PIM, and inhibitors of NF-κB in models of chemotherapy resistance.

Immunotherapy

A renal cell carcinoma (lower left) in a kidney

Main article: Cancer immunotherapy

Further information: Bladder cancer § Immunotherapy

Cancer immunotherapy refers to a diverse set of therapeutic strategies designed to induce the patient's own immune system to fight the tumor. Contemporary methods for generating an immune response against tumors include intravesical BCG immunotherapy for superficial bladder cancer, and use of interferons and other cytokines to induce an immune response in renal cell carcinoma and melanoma patients. Cancer vaccines to generate specific immune responses are the subject of intensive research for a number of tumors, notably malignant melanoma and renal cell carcinoma. Sipuleucel-T is a vaccine-like strategy for prostate cancer in which dendritic cells from the patient are loaded with prostatic acid phosphatase peptides to induce a specific immune response against prostate-derived cells. It gained FDA approval in 2010.

Allogeneic hematopoietic stem cell transplantation (usually from the bone marrow) from a genetically non-identical donor can be considered a form of immunotherapy, since the donor's immune cells will often attack the tumor in a phenomenon known as graft-versus-tumor effect. For this reason, allogeneic HSCT leads to a higher cure rate than autologous transplantation for several cancer types, although the side effects are also more severe.

The cell based immunotherapy in which the patients own natural killer cells (NKs) and cytotoxic T cells are used has been in practice in Japan since 1990. NK cells and TCs primarily kill the cancer cells when they are developed. This treatment is given together with the other modes of treatment such as surgery, radiotherapy or chemotherapy and termed autologous immune enhancement therapy (AIET).

Immune checkpoint therapy focuses on two immune checkpoint proteins, cytotoxic T-lymphocyte associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1). Under normal conditions, the immune system utilizes checkpoint proteins as negative feedback mechanisms to return to homeostasis once pathogens have been cleared from the body. In a tumor microenvironment, cancer cells can commandeer this physiological regulatory system to "put a brake" on the anti-cancer immune response and evade immune surveillance. 2018 Nobel Prize in medicine is awarded to Dr. James Allison of University of Texas MD Anderson Cancer Center in U.S. and Dr. Tasuku Honjo Kyoto University in Japan for their contributions in advance of PD-1 and CTLA-4 immune checkpoint therapy.

Hormonal therapy

Main article: Hormonal therapy (oncology)

The growth of some cancers can be inhibited by providing or blocking certain hormones. Common examples of hormone-sensitive tumors include certain types of breast and prostate cancers. Blocking estrogen or testosterone is often an important additional treatment. In certain cancers, administration of hormone agonists, such as progestogens may be therapeutically beneficial. Although the side effects from hormone therapy vary depending on the type, patients can experience symptoms such as hot flashes, nausea, and fatigue.

Angiogenesis inhibitors

Main article: Angiogenesis inhibitor

Angiogenesis inhibitors prevent the extensive growth of blood vessels (angiogenesis) that tumors need to survive and grow. Continued growth allows the invasion of cells into neighbouring tissues, and metastasis into distal tissues. There are many approved angiogenesis inhibitors including bevacizumab, axitinib, and cabozantinib.

Flavonoids have been shown to downregulate the angiogenic stimulation of VEGF and Hypoxia-inducible factor (HIF) but none have reached clinical trials.

Exercise prescription

Main article: Exercise prescription

Exercise prescription is becoming a mainstream adjunct treatment for cancer, based on studies which show that exercise (compared to no exercise) is associated with reduced recurrence rates, improved mortality outcomes, reduction of side effects from traditional cancer treatments. Although it is uncertain whether improved outcomes with exercise are correlated or causative, the benefit-risk ratio of including exercise as part of cancer treatment is large, as exercise has further benefits (e.g. cardiovascular, mental health) without major risks, although there is a small risk of overuse injury if added too aggressively. Exercise physiologists and exercise medicine specialists can assist oncologists and primary care practitioners with exercise prescription in cancer patients.

Walking is usually an excellent exercise option as an adjunct cancer treatment

Synthetic lethality

Main article: Synthetic lethality

Synthetic lethality arises when a combination of deficiencies in the expression of two or more genes leads to cell death, whereas a deficiency in only one of these genes does not. The deficiencies can arise through mutations, epigenetic alterations or inhibitors of one or both of the genes.

Cancer cells are frequently deficient in a DNA repair gene. (Also see DNA repair deficiency in cancer.) This DNA repair defect either may be due to mutation or, often, epigenetic silencing (see epigenetic silencing of DNA repair). If this DNA repair defect is in one of seven DNA repair pathways (see DNA repair pathways), and a compensating DNA repair pathway is inhibited, then the tumor cells may be killed by synthetic lethality. Non-tumorous cells, with the initial pathway intact, can survive.

Ovarian cancer

Main article: Ovarian cancer

Mutations in DNA repair genes BRCA1 or BRCA2 (active in homologous recombinational repair) are synthetically lethal with inhibition of DNA repair gene PARP1 (active in the base excision repair and in the microhomology-mediated end joining pathways of DNA repair).

Ovarian cancers have a mutational defect in BRCA1 in about 18% of patients (13% germline mutations and 5% somatic mutations) (see BRCA1). Olaparib, a PARP inhibitor, was approved in 2014 by the US FDA for use in BRCA-associated ovarian cancer that had previously been treated with chemotherapy. The FDA, in 2016, also approved the PARP inhibitor rucaparib to treat women with advanced ovarian cancer who have already been treated with at least two chemotherapies and have a BRCA1 or BRCA2 gene mutation.

Colon cancer

Main article: Colorectal cancer

In colon cancer, epigenetic defects in the WRN gene appear to be synthetically lethal with inactivation of TOP1. In particular, irinotecan inactivation of TOP1 was synthetically lethal with deficient expression of the DNA repair WRN gene in patients with colon cancer. In a 2006 study, 45 patients had colonic tumors with hypermethylated WRN gene promoters (silenced WRN expression), and 43 patients had tumors with unmethylated WRN gene promoters, so that WRN protein expression was high. Irinotecan was more strongly beneficial for patients with hypermethylated WRN promoters (39.4 months survival) than for those with unmethylated WRN promoters (20.7 months survival). The WRN gene promoter is hypermethylated in about 38% of colorectal cancers.

There are five different stages of colon cancer, and these five stages all have treatment:

• Stage 0, is where the patient is required to undergo surgery to remove the polyp (American Cancer Society).
• Stage 1, depending on the location of the cancer in the colon and lymph nodes, the patient undergoes surgery just like Stage 0.
• Stage 2 patients undergoes removing nearby lymph nodes, but depending on what the doctor says, the patent might have to undergo chemotherapy after surgery (if the cancer is at higher risk of coming back).
• Stage 3, is where the cancer has spread all throughout the lymph nodes but not yet to other organs or body parts. When getting to this stage, Surgery is conducted on the colon and lymph nodes, then the doctor orders Chemotherapy (FOLFOX or CapeOx) to treat the colon cancer in the location needed (American Cancer Society). The last a patient can get is Stage 4.
• Stage 4 patients only undergo surgery if it is for the prevention of the cancer, along with pain relief. If the pain continues with these two options, the doctor might recommended radiation therapy. The main treatment strategy is chemotherapy due to how aggressive the cancer becomes in this stage, not only to the colon but to the lymph nodes.

Symptom control and palliative care

Further information: Cancer pain § Management

Although the control of the symptoms of cancer is not typically thought of as a treatment directed at the cancer, it is an important determinant of the quality of life of cancer patients, and plays an important role in the decision whether the patient is able to undergo other treatments. In general, doctors have the therapeutic skills to reduce pain including, chemotherapy-induced nausea and vomiting, diarrhea, hemorrhage and other common problems in cancer patients. The multidisciplinary specialty of palliative care has increased specifically in response to the symptom control needs for these groups of patients.

Pain medication, such as morphine, oxycodone, and antiemetics are drugs to suppress nausea and vomiting. These are very commonly used in patients with cancer-related symptoms. Improved antiemetics such as ondansetron and analogues, as well as aprepitant have made aggressive treatments much more feasible in cancer patients.

Cancer pain can be associated with continuing tissue damage due to the disease process, or the treatment (i.e. surgery, radiation, chemotherapy). There is always a role for environmental factors and affective disturbances in the genesis of pain behaviors, However these are not usually the predominant etiologic factors in patients with cancer pain. Some patients with severe pain associated with cancer are nearing the end of their lives, but in all cases, palliative therapies should be used to control the pain. Issues such as the social stigma of using opioids and health care consumption can be concerns and may need to be addressed for the person to feel comfortable taking the medications required to control his or her symptoms. The typical strategy for cancer pain management is to get the patient as comfortable as possible using the least amount of medications possible, even if that means using opioids, surgery, and physical measures.

Historically, doctors were reluctant to prescribe narcotics to terminal cancer patients due to addiction and respiratory function suppression. The palliative care movement, a more recent offshoot of the hospice movement, has engendered more widespread support for preemptive pain treatment for cancer patients. The World Health Organization also noted uncontrolled cancer pain as a worldwide problem and established a "ladder" as a guideline for how practitioners should treat pain in patients who have cancer

Cancer-related fatigue is a very common symptom of cancer, and there are a number of approaches put forward for helping with this.

Mental struggles/pain

Cancer patients undergo many obstacles and one of these includes mental strain. It is very common for cancer patients to become stressed, overwhelmed, uncertain, and even depressed. The use of chemo is a very harsh treatment causing the cells of the body to die. Physical effects like this do not only inflict pain but also cause patients to become mentally exhausted and want to give up. For a lot of reasons including these, hospitals offer many types of therapy and mental healing. Some of these include yoga, meditation, communication therapy, and spiritual ideas. All of these are meant to calm and relax the mind, or to give hope for the patients that may feel drained.

Insomnia

A common disorder experienced by people that have survived cancer treatments is insomnia. Almost 60% of cancer survivors experience insomnia, and if it is not treated properly it can have long term effects on physiological and physical health. Insomnia is defined as dissatisfaction with sleep duration or quality and difficulties initiating or maintaining sleep. Insomnia can heavily reduce one's quality of life. Cognitive behavioral therapy has been seen to reduce insomnia and depression for cancer survivors.

Muscle strength

Decreased muscle strength is a common side effect to many different cancer treatments. Because of this, exercise is very important especially in the first year after treatment. It has been shown that yoga, water exercise, and pilates can improve the emotional well-being and quality of life of breast cancer survivors.

Hospice care

Hospice care provides palliative care at home, or in a dedicated hospice institution, for a person with an advanced illness termed as terminal. Untreated cancer will prove terminal, and sometimes a choice is made to forgo treatment and its unpleasant side effects, and opt instead for hospice care. Hospice care aims to provide support for the person's medical, emotional, social, practical, psychological, and spiritual needs.

Advance care planning (ACP) can help a person to decide for themself their future care wishes as they approach end of life. ACP helps adults at any stage of health to decide, and record in writing, their wishes for medical treatment preferences, and future wants, preferably as previously discussed with relatives or carers.

Research

Main article: Experimental cancer treatment

Clinical trials, also called research studies, test new treatments in people with cancer. The goal of this research is to find better ways to treat cancer and help cancer patients. Clinical trials test many types of treatment such as new drugs, new approaches to surgery or radiation therapy, new combinations of treatments, or new methods such as gene therapy.

A clinical trial is one of the final stages of a long and careful cancer research process. The search for new treatments begins in the laboratory, where scientists first develop and test new ideas. If an approach seems promising, the next step may be testing a treatment in animals to see how it affects cancer in a living being and whether it has harmful effects. Of course, treatments that work well in the lab or in animals do not always work well in people. Studies are done with cancer patients to find out whether promising treatments are safe and effective.

Patients who take part may be helped personally by the treatment they receive. They get up-to-date care from cancer experts, and they receive either a new treatment being tested or the best available standard treatment for their cancer. At the same time, new treatments also may have unknown risks, but if a new treatment proves effective or more effective than standard treatment, study patients who receive it may be among the first to benefit. There is no guarantee that a new treatment being tested or a standard treatment will produce good results. In children with cancer, a survey of trials found that those enrolled in trials were on average not more likely to do better or worse than those on standard treatment; this confirms that success or failure of an experimental treatment cannot be predicted.

Exosome research

Exosomes are lipid-covered microvesicles shed by solid tumors into bodily fluids, such as blood and urine. Current research is being done attempting to use exosomes as a detection and monitoring method for a variety of cancers. The hope is to be able to detect cancer with a high sensitivity and specificity via detection of specific exosomes in the blood or urine. The same process can also be used to more accurately monitor a patient's treatment progress. Enzyme linked lectin specific assay or ELLSA Archived 13 July 2011 at the Wayback Machine has been proven to directly detect melanoma derived exosomes from fluid samples. Previously, exosomes had been measured by total protein content in purified samples and by indirect immunomodulatory effects. ELLSA directly measures exosome particles in complex solutions, and has already been found capable of detecting exosomes from other sources, including ovarian cancer and tuberculosis-infected macrophages.

Exosomes, secreted by tumors, are also believed to be responsible for triggering programmed cell death (apoptosis) of immune cells; interrupting T-cell signaling required to mount an immune response; inhibiting the production of anti-cancer cytokines, and has implications in the spread of metastasis and allowing for angiogenesis. Studies are currently being done with "Lectin affinity plasmapheresis" (LAP), LAP is a blood filtration method which selectively targets the tumor based exosomes and removes them from the bloodstream. It is believed that decreasing the tumor-secreted exosomes in a patient's bloodstream will slow down progression of the cancer while at the same time increasing the patients own immune response.

Complementary and alternative

Main article: Alternative cancer treatments

Complementary and alternative medicine (CAM) treatments are the diverse group of medical and health care systems, practices, and products that are not part of conventional medicine and have not been shown to be effective. "Complementary medicine" refers to methods and substances used along with conventional medicine, while "alternative medicine" refers to compounds used instead of conventional medicine. CAM use is common among people with cancer; a 2000 study found that 69% of cancer patients had used at least one CAM therapy as part of their cancer treatment. Most complementary and alternative medicines for cancer have not been rigorously studied or tested. Some alternative treatments which have been investigated and shown to be ineffective continue to be marketed and promoted.

Special circumstances

In pregnancy

The incidence of pregnancy-associated cancer has risen due to the increasing age of pregnant mothers. Cancers may also be detected incidentally during maternal screening.

Cancer treatment needs to be selected to do least harm to both the woman and her embryo/fetus. In some cases a therapeutic abortion may be recommended.

Radiation therapy is out of the question, and chemotherapy always poses the risk of miscarriage and congenital malformations. Little is known about the effects of medications on the child.

Even if a drug has been tested as not crossing the placenta to reach the child, some cancer forms can harm the placenta and make the drug pass over it anyway. Some forms of skin cancer may even metastasize to the child's body.

Diagnosis is also made more difficult, since computed tomography is infeasible because of its high radiation dose. Still, magnetic resonance imaging works normally. However, contrast media cannot be used, since they cross the placenta.

As a consequence of the difficulties to properly diagnose and treat cancer during pregnancy, the alternative methods are either to perform a Cesarean section when the child is viable in order to begin a more aggressive cancer treatment, or, if the cancer is malignant enough that the mother is unlikely to be able to wait that long, to perform an abortion in order to treat the cancer.

In utero

Fetal tumors are sometimes diagnosed while still in utero. Teratoma is the most common type of fetal tumor, and usually is benign. In some cases these are surgically treated while the fetus is still in the uterus.

Racial and social disparities

Cancer is a significant issue that is affecting the world. Specifically in the U.S, it is expected for there to be 1,735,350 new cases of cancer, and 609,640 deaths by the end of 2018. Adequate treatment can prevent many cancer deaths but there are racial and social disparities in treatments which has a significant factor in high death rates. Minorities are more likely to receive inadequate treatment while white patients are more likely to receive efficient treatments in a timely manner. Having satisfactory treatment in timely manner can increase the patients likelihood of survival. It has been shown that chances of survival are significantly greater for white patients than for African American patients.

The annual average mortality of patients with colorectal cancer between 1992 and 2000 was 27 and 18.5 per 100,000 white patients and 35.4 and 25.3 per 100,000 black patients. In a journal that analyzed multiple studies testing racial disparities when treating colorectal cancer found contradicting findings. The Veterans administration and an adjuvant trial found that there were no evidence to support racial differences in treating colorectal cancer. However, two studies suggested that African American patients received less satisfactory and poor quality treatment compared to white patients. One of these studies specifically was provided by the Center for Intramural Research. They found that black patients were 41% less likely to receive colorectal treatment and were more likely to be hospitalized in a teaching hospital with less certified physicians compared to white patients. Furthermore, black patients were more likely to be diagnosed with oncologic sequelae, which is a severity of the illness in result of poorly treated cancer. Lastly, for every 1,000 patients in the hospital, there were 137.4 black patient deaths and 95.6 white patient deaths.

In a breast cancer journal article analyzed the disparities of breast cancer treatments in the Appalachian Mountains. African American women were found to be 3 times more likely to die compared to Asians and two times more likely to die compared to white women. According to this study, African American women are at a survival disadvantage compared to other races. Black women are also more likely to receive less successful treatment than white women by not receiving surgery or therapy. Furthermore, The National Cancer Institute panel, identified breast cancer treatments, given to black women, as inappropriate and not adequate compared to the treatment given to white women.

From these studies, researchers have noted that there are definite disparities in the treatment of cancer, specifically who have access to the best treatment and can receive it in a timely manner. This eventually leads to disparities between who is dying from cancer and who is more likely to survive.

The cause of these disparities is generally that African Americans have less medical care coverage, insurance and access cancer centers than other races. For an example, black patients with breast cancer and colorectal cancer were shown to be more likely to have medicaid or no insurance compared to other races. The location of the health care facility also plays a role in why African Americans receive less treatment in comparison to other races. However, some studies say that African Americans don't trust doctors and don't always seek the help they need and this explains why there are less African Americans receiving treatment. Others suggest that African Americans seek even more treatment than whites and that it is simply a lack of the resources available to them. In this case, analyzing these studies will identify the treatment disparities and look to prevent them by discovering potential causes of these disparities.