Despite significant progress in the treatment of certain forms of cancer (such as childhood leukemia), cancer in general remains a major cause of death 40+ years after this war on cancer began, leading to a perceived lack of progress and to new legislation aimed at augmenting the original National Cancer Act of 1971.
New research directions, in part based on the results of the Human Genome Project, hold promise for a better understanding of the genetic factors underlying cancer, and the development of new diagnostics, therapies, preventive measures, and early detection ability. However, targeting cancer proteins can be difficult, as a protein can be undruggable.
History
National Cancer Act of 1971
The war on cancer began with the National Cancer Act of 1971, a United States federal law.
The act was intended "to amend the Public Health Service Act so as to strengthen the National Cancer Institute in order to more effectively carry out the national effort against cancer".
It was signed into law by President Nixon on December 23, 1971.
Health activist and philanthropist Mary Lasker was instrumental in persuading the United States Congress to pass the National Cancer Act. She and her husband Albert Lasker
were strong supporters of medical research. They established the Lasker
Foundation which awarded people for their research. In the year of
1943, Mary Lasker began changing the American Cancer Society to get more
funding for research. Five years later she contributed to getting
federal funding for the National Cancer Institute and the National Heart
Institute. In 1946 the funding was around $2.8 million and had grown to
over $1.4 billion by 1972. In addition to all of these
accomplishments, Mary became the president of the Lasker Foundation due
to the death of her husband in 1952. Lasker's devotion to medical
research and experience in the field eventually contributed to the
passing of the National Cancer Act.
The improved funding for cancer research has been quite
beneficial over the last 40 years. In 1971, the number of survivors in
the U.S. was 3 million and as of 2007 has increased to more than 12
million.
NCI Director's Challenge
In 2003, Andrew von Eschenbach, the director of the National Cancer Institute (who served as FDA Commissioner from 2006-2009 and is now a Director at biotechnology company BioTime) issued a challenge "to eliminate the suffering and death from cancer, and to do so by 2015".
This was supported by the American Association for Cancer Research in 2005
though some scientists felt this goal was impossible to reach and undermined von Eschenbach's credibility.
John E. Niederhuber,
who succeeded Andrew von Eschenbach as NCI director, noted that cancer
is a global health crisis, with 12.9 million new cases diagnosed in 2009
worldwide and that by 2030, this number could rise to 27 million
including 17 million deaths "unless we take more pressing action."
Harold Varmus, former director of the NIH and current director of the NCI,
held a town hall meeting in 2010
in which he outlined his priorities for improving the cancer research program, including the following:
- reforming the clinical trials system,
- improving utilization of the NIH clinical center (Mark O. Hatfield Clinical Research Center),
- readjusting the drug approval and regulation processes,
- improving cancer treatment and prevention, and
- formulating new, more specific and science-based questions.
Renewed focus on cancer
Recent
years have seen an increased perception of a lack of progress in the
war on cancer, and renewed motivation to confront the disease.
On July 15, 2008, the United States Senate Committee on Health, Education, Labor, and Pensions convened a panel discussion titled, Cancer: Challenges and Opportunities in the 21st Century.
It included interviews with noted cancer survivors such as Arlen Specter, Elizabeth Edwards and Lance Armstrong, who came out of retirement in 2008, returning to competitive cycling "to raise awareness of the global cancer burden."
Livestrong Foundation
The Livestrong Foundation
created the Livestrong Global Cancer Campaign to address the burden of
cancer worldwide and encourage nations to make commitments to battle the
disease and provide better access to care.
In April 2009, the foundation announced that the Hashemite Kingdom of Jordan
pledged $300 million to fund three important cancer control initiatives
– building a cutting-edge cancer treatment and research facility,
developing a national cancer control plan and creating an Office of
Advocacy and Survivorship.
The Livestrong Foundation encourages similar commitments from other nations to combat the disease.
Livestrong Day is an annual event established by the LAF to serve
as "a global day of action to raise awareness about the fight against
cancer." Individuals from around the world are encouraged to host
cancer-oriented events in their local communities and then register
their events with the Livestrong website.
21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act
The US Senate on 26 March 2009 issued a new bill (S. 717), the 21st Century Cancer Access to Life-Saving Early detection, Research and Treatment (ALERT) Act
intended to "overhaul the 1971 National Cancer Act."
The bill aims to improve patient access to prevention and early detection by:
- providing funding for research in early detection,
- supplying grants for screening and referrals for treatment, and
- increasing access to clinical trials and information.
Obama-Biden Plan to Combat Cancer
During their 2008 U.S. presidential campaign then Senators Barack Obama and Joe Biden published a plan to combat cancer that entailed doubling "federal funding for cancer research within 5 years, focusing on NIH and NCI" as well as working "with Congress to increase funding for the
Food and Drug Administration."
Their plan would provide additional funding for:
- research on rare cancers and those without effective treatment options,
- the study of health disparities and evaluation of possible interventions,
- and efforts to better understand genetic factors that can impact cancer onset and outcomes.
President Obama's 2009 economic stimulus package includes $10 billion for the NIH, which funds much of the cancer research
in the U.S., and he has pledged to increase federal funding for cancer
research by a third for the next two years as part of a drive to find "a
cure for cancer in our time."
In a message published in the July 2009 issue of Harper's Bazaar, President Obama described his mother's battle with ovarian cancer
and, noting the additional funding his administration has slated for
cancer research, stated: "Now is the time to commit ourselves to waging a
war against cancer as aggressive as the war cancer wages against us."
On 30 September 2009, Obama announced that $1 billion of a $5 billion
medical research spending plan would be earmarked for research into the
genetic causes of cancer and targeted cancer treatments.
Cancer-related federal spending of money from the 2009 Recovery Act can be tracked online.
World Cancer Campaign
The International Union Against Cancer (UICC)
has organized a World Cancer campaign in 2009 with the theme, "I love
my healthy active childhood," to promote healthy habits in children and
thereby reduce their lifestyle-based cancer risk as adults.
The World Health Organization is also promoting this campaign
and joins with the UICC in annually promoting World Cancer Day on 4 February.
Progress
Though there has been significant progress in the understanding of cancer biology, risk factors, treatments, and prognosis of some types of cancer (such as childhood leukemia) since the inception of the National Cancer Act of 1971, progress in reducing the overall cancer mortality rate has been disappointing. Many types of cancer remain largely incurable (such as pancreatic cancer)
and the overall death rate from cancer has not decreased appreciably since the 1970s.
The death rate for cancer in the U.S., adjusted for population size and age, dropped only 5 percent from 1950 to 2005. Cancer was expected to surpass cardiovascular disease as the leading cause of death in the world by 2010, according to the World Health Organization's World Cancer Report 2008. As of 2012, WHO reported 8.2 million annual deaths from cancer
Heart disease (including both Ischaemic and hypertensive) accounted for
8.5 million annual deaths. Stroke accounted for 6.7 million annual
deaths.
There is evidence for progress in reducing cancer mortality.
Age-specific analysis of cancer mortality rates has had progress in
reducing cancer mortality in the United States since 1955. An August
2009 study found that age-specific cancer mortality rates have been
steadily declining since the early 1950s for individuals born since
1925, with the youngest age groups experiencing the steepest decline in
mortality rate at 25.9 percent per decade, and the oldest age groups
experiencing a 6.8 percent per decade decline.
Dr. Eric Kort, the lead author of this study, claims that public reports
often focus on cancer incidence rates and under appreciate the progress
that has been achieved in reduced cancer mortality rates.
The effectiveness and expansion of available therapies has seen significant improvements since the 1970s. For example, lumpectomy replaced more invasive mastectomy surgery for the treatment of breast cancer.
Treatment of childhood leukemia and chronic myeloid leukemia (CML) have undergone major advances since the war on cancer began. The drug Gleevec now cures most CML patients, compared to previous therapy with interferon, which extended life for approximately 1 year in only 20-30 percent of patients.
Dr. Steven Rosenberg, chief of surgery at the NCI has said that as of the year 2000, 50% of all diagnosed cases of cancer are curable
through a combination of surgery, radiation, and chemotherapy.
Cancer surveillance experts have reported a 15.8 percent decrease in
the age-standardized death rate from all cancers combined between 1991
and 2006 along with an approximately 1 percent annual decrease in the
rate of new diagnoses between 1999 and 2006. A large portion of this decreased mortality for men was attributable to smoking cessation efforts in the United States.
A 2010 report from the American Cancer Society
found that death rates for all cancers combined decreased 1.3% per year
from 2001 to 2006 in males and 0.5% per year from 1998 to 2006 in
females, largely due to decreases in the 3 major cancer sites in men
(lung, prostate, and colorectum) and 2 major cancer sites in women
(breast and colorectum). Cancer death rates between 1990 and 2006 for
all races combined decreased by 21.0% among men and by 12.3% among
women. This reduction in the overall cancer death rates translates to
the avoidance of approximately 767,000 deaths from cancer over the
16-year period. Despite these reductions, the report noted, cancer still
accounts for more deaths than heart disease in persons younger than 85 years.
An improvement in the number of cancer survivors living in the U.S. was indicated in a 2011 report by the CDC and the NCI,
which noted that the number of cancer survivors in 2007 (11.7 million)
increased by 19% from 2001 (9.8 million survivors). The number of cancer
survivors in 1971 was 3 million. Breast, prostate, and colorectal
cancers were the most common types of cancer among survivors,
accounting for 51% of diagnoses. As of January 1, 2007, an estimated
64.8% of cancer survivors had lived ≥5 years after their diagnosis of
cancer, and 59.5% of survivors were aged ≥65 years.
A continued decline in cancer rates in the U.S. among both women and
men, across most major racial groups, and in the most common cancer
sites (lung, colon and rectum), was indicated in a 2013 report by the
National Cancer Institute. However, the same report indicated an
increase from 2000 to 2009 in cancers of the liver, pancreas and uterus.
Challenges
A multitude of factors have been cited as impeding progress in finding a cure for cancer and key areas have been identified and suggested as important to accelerate progress in cancer research.
Since there are many different forms of cancer with distinct causes,
each form requires different treatment approaches. However, this
research could still lead to therapies and cures for many forms of
cancer. Some of the factors that have posed challenges for the
development of preventive measures and anti-cancer drugs and therapies include the following:
- Inherent biological complexity of the disease:
- number of changes within a cell leading to the cancerous state
- disease heterogeneity due to different tissues of origin
- contribution of numerous genetic and environmental risk factors
- complexity of cellular interactions and cell signaling within the tumor microenvironment
- suitability of model organisms for understanding human disease.
- Roadblocks to translational medicine
- Challenges of early detection and diagnosis
- The drug approval process
- Availability of and access to patients with suitable tumor tissue for research
- Challenges in implementing preventive measures, such as the development and use of preventive drugs and therapies
- Choropleth mapping of the changes over time, of the national incidence rate, by cancer type, relative to the population at risk, is a technical challenge.
“The public is so jaded by cancer research media attention at the moment... And let’s face it, rather embarrassingly, most claimed ‘breakthroughs’ are not proving to significantly advance cancer therapies... It is a real conundrum for researchers today, because ‘early publicity’ is needed for funding, capital raising and professional kudos, but not too helpful for the public who then think that an immediate cure might be just around the corner.” Professor Brendon Coventry, 9 July 2013
Modern cancer research
Genome-based cancer research projects
The rise of a new class of molecular technologies developed during the Human Genome Project
opens up new ways to study cancer and holds the promise for the
discovery of new aspects of cancer biology that could eventually lead to
novel, more effective diagnostics and therapies for cancer patients.
These new technologies are capable of screening many biomolecules and genetic variations such as SNPs
and copy number variations in a single experiment and are employed within functional genomics and personalized medicine studies.
Speaking on the occasion of the announcement of $1 billion in new funding for genome-based cancer research, Dr. Francis Collins, director of the NIH claimed, "We are about to see a quantum leap in our understanding of cancer." Harold Varmus, after his appointment to be the director of the NCI, said we are in a "golden era for cancer research," poised to profit from advances in our understanding of the cancer genome.
High-throughput DNA sequencing has been used to study the whole genome sequence of two different cancer tissues: a small-cell lung cancer metastasis and a malignant melanoma cell line.
The sequence information provides a comprehensive catalog of approximately 90% of the somatic
mutations in the cancerous tissue, providing a more detailed molecular
and genetic understanding of cancer biology than was previously
possible, and offering hope for the development of new therapeutic
strategies gleaned from these insights.
The Cancer Genome Atlas
The Cancer Genome Atlas (TCGA), a collaborative effort between the National Cancer Institute and the National Human Genome Research Institute, is an example of a basic research project that is employing some of these new molecular approaches.
One TCGA publication notes the following:
Here we report the interim integrative analysis of DNA copy number, gene expression and DNA methylation aberrations in 206 glioblastomas...Together, these findings establish the feasibility and power of TCGA, demonstrating that it can rapidly expand knowledge of the molecular basis of cancer.
In a cancer research funding announcement made by president Obama in
September 2009, TCGA project is slated to receive $175 million in
funding to collect comprehensive gene sequence data on 20,000 tissue
samples from people with more than 20 different types of cancer, in
order to help researchers understand the genetic changes underlying
cancer. New, targeted therapeutic approaches are expected to arise from
the insights resulting from such studies.
Cancer Genome Project
The Cancer Genome Project at the Wellcome Trust Sanger Institute aims to identify sequence variants/mutations critical in the development of human cancers. The Cancer Genome Project combines knowledge of the human genome sequence with high throughput mutation detection techniques.
Cancer research supportive infrastructure
Advances in information technology supporting cancer research, such as the NCI's caBIG
project, promise to improve data sharing among cancer researchers and
accelerate "the discovery of new approaches for the detection,
diagnosis, treatment, and prevention of cancer, ultimately improving patient outcomes."
Modern cancer treatment
Cancer clinical trials
Researchers
are considering ways to improve the efficiency, cost-effectiveness, and
overall success rate of cancer clinical trials.
Increased participation in rigorously designed clinical trials
would increase the pace of research. Currently, about 3% of people with
cancer participate in clinical trials; more than half of them are
patients for whom no other options are left, patients who are
participating in "exploratory" trials designed to burnish the
researchers' résumés or promote a drug rather than to produce meaningful
information, or in trials that will not enroll enough patients to
produce a statistically significant result.
Targeted tumor treatment
A major challenge in cancer treatment is to find better ways to specifically target tumors with drugs and chemotherapeutic agents
in order to provide a more effective, localized dose and to minimize
exposure of healthy tissue in other parts of the body to the potentially
adverse effects of the treatments. The accessibility of different
tissues and organs to anti-tumor drugs contributes to this challenge.
For example, the blood–brain barrier
blocks many drugs that may otherwise be effective against brain tumors.
In November 2009, a new, experimental therapeutic approach for treating
glioblastoma was published in which the anti-tumor drug Avastin was delivered to turmor site within the brain through the use of microcatheters, along with mannitol to temporarily open the blood–brain barrier permitting delivery of the chemotherapy into the brain.
Public education and support
An
important aspect to the war on cancer is improving public access to
educational and supportive resources, to provide individuals with the
latest information about cancer prevention and treatment,
as well as access to support communities. Resources have been created
by governmental and other organizations to provide support for cancer
patients, their families and caregivers, to help them share information
and find advice to guide decision making.
