40 Years of the War on Cancer

War on Cancer is still ongoing, however, we have seen some progress which is significant, at least for those who have benefited from all these developments. A nice article (published in Science magazine) summarizes important feats that cancer researchers achieved in the last 40 years:

 (Courtesy: Science  25 March 2011: Vol. 331 no. 6024 pp. 1540-1544 )

Timeline

1971

PHOTO: LINDA BARTLETT/NCI

President Richard Nixon signs the National Cancer Act promoting the National Cancer Institute.

1973

NCI launches Surveillance Epidemiology and End Results program to collect U.S. cancer data.

1978

PHOTO: BILL BRANSON/NCI

Clinical testing begins of interferon-α, the first biological cancer therapy. FDA approves tamoxifen to prevent breast cancer recurrence.

1979

Researchers discover p53, the mutated gene most often seen in tumors.

1980

PHOTO: NCI

Robert Gallo and others isolate human T-cell lymphotropic virus-1, a cause of cancer.

1981

First cancer-prevention vaccine introduced— against human hepatitis B virus.

1983

Researchers create severe combined immunodeficient mice, a model for cancer research.

1985

PHOTO: NCI

Randomized trial shows that lumpectomy plus radiation are as effective as mastectomy for breast cancer.

1986

Biostatistician John Bailar writes in The New England Journal of Medicine, “We are losing the war against cancer.”

1989

PHOTO: PAUL SAKUMA/AP

Nobel Prize for discovering the first proto-oncogene (Src) awarded to Harold Varmus and Michael Bishop.

1991

National Breast Cancer Coalition launched, in the AIDS activist style.

1992

PHOTO: GEORGE MCGREGOR/NCI

FDA approves synthetic yew bark derivative, Taxol (paclitaxel), for breast cancer.

1993

PHOTO: SCIENCE

Congress orders study of environmental causes of breast cancer on Long Island; the 10-year study will yield no significant findings. Science names p53 “Molecule of the Year.”

1994

BRCA1 gene, identified as a risk for breast and ovarian cancer, is cloned; BRCA2 cloned the next year.

1996

American Cancer Society and others report the “first sustained decline” in overall U.S. cancer deaths, a drop of 2.6% from 1991 to 1995.

1998

FDA approves Herceptin (trastuzumab), a monoclonal antibody, for metastatic breast tumors that overproduce HER2.

1998

PHOTO: NCI

Nobelist James Watson tells The New York Times that blocking the growth of tumor blood vessels (antiangiogenesis) can “cure cancer in 2 years.”

2001

FDA approves Gleevec (imatinib), a targeted drug, for chronic myelogenous leukemia; Time calls it a “magic bullet.”

2003

PHOTO: GLOGAU PHOTOGRAPHY/NCI

NCI Director Andrew von Eschenbach vows to “eliminate suffering and death from cancer by 2015.”

2004

FDA approves Avastin, an antiangiogenesis drug, for colon cancer, with chemotherapy. Childhood cancer landmark: nearly 80% of those treated for acute lymphoblastic leukemia are free of cancer “events” for 5 years or more.

2005

CREDIT: NCI

NIH launches The Cancer Genome Atlas to catalog genomic changes in tumors.

2006

FDA approves Gardasil vaccine to prevent HPV infection, which can lead to cervical cancer.

2007–2008

Breast cancer incidence declines, attributed to better screening and reduced use of hormone replacement therapy.

2009

James Watson writes that it's time to turn from cancer genetics to “understanding the chemical reactions within cancer cells,” or cell metabolism.

2010

PHOTO: JUPITER IMAGES/THINKSTOCK

National Lung Cancer Screening Trial finds that helical CT screening can reduce cancer deaths among smokers. FDA approves Provenge, an immune treatment for metastatic prostate cancer. It extends life about 4 months and costs $93,000.

2011

PLX4032, a targeted cancer drug, extends life in patients with advanced melanoma.

Translational medicine: a hope for patients with Pancreatic Neuroendocrine Tumors

Pancreatic neuroendocrine tumors (also known as Islet cell carcinoma) or PNETs are a type of neuroendocrine tumor found in the pancreas. Only 5 percent of pancreatic tumors arise in the islet cells. The vast majority of tumors found in the pancreas are adenocarcinoma, which is more commonly referred to as pancreatic cancer.  PNETs are very uncommon though, but are very difficult to diagnose and treat. These cancers, which originate from the hormone-producing pancreatic islet cells, stand in stark contrast to another type of pancreatic cancer, pancreatic ductal adenocarcinoma, which is much more prevalent and deadly: a larger proportion of patients with PNET undergo surgical excision, and the clinical course of the disease is highly variable. Nonetheless, patients with advanced PNET who are not candidates for surgery have a terminal illness, and their tumors are difficult to manage. So for only few chemotherapeutic agents are  available to treat PNET but they have only modest activity in these patients.

Two recent translational studies published back to back in 10 Feb issue of NEJM show a ray of hope for the patients with these tumors. One study conducted by Dr. Eric Raymond concluded that Continuous daily administration of sunitinib (a multi-tyrosine kinase inhibitor) at a dose of 37.5 mg improved progression- free survival, overall survival, and the objective response rate as compared with placebo among patients with advanced pancreatic neuroendocrine tumors.

http://www.nejm.org/doi/full/10.1056/NEJMoa1003825#t=abstract

While other study by Yao and colleagues  demonstrated that Everolimus which acts as an oral inhibitor of mammalian target of rapamycin (mTOR),, as compared with placebo, significantly prolonged progression-free survival among patients with progressive advanced pancreatic neuroendocrine tumors and was associated with a low rate of severe adverse events. Although it must be taken with pinch of salt as Yao and colleagues note that, whereas everolimus delays time to progression of the disease (progression-free survival), it seemingly does not increase overall survival rates. This trial is still ongoing, however, so the lack of effect on overall survival is not yet conclusive.

http://www.nejm.org/doi/full/10.1056/NEJMoa1009290#t=abstract

These clinical trails, however, have their own limitations and moderate success rate, can be considered as landmarks for treating PNET. The approach that led to this — a long and well designed preclinical studies to elucidate the pathways underlying the disease and mechanism of tumor progression in a representative mouse model and human clinical trials — could also be used to test the efficacy of other anticancer drugs and may well replicate this success story. This strategy from going to preclinical studies to clinical trials is certainly going to prove as model study for other similar investigations in future in which preclinical trials in genetically engineered mouse models, and in other representative animal models, could guide the development of more effective therapies for human cancers, revealing efficacy, beneficial drug combinations and mechanisms of therapeutic resistance.

an interesting article debating the "viral roots of chronic fatigue syndrome"

http://www.nature.com/news/2011/110314/pdf/471282a.pdf

A Journal to Publish Unpublished Data........

I hope no one who ever has done scientific research especially biomedical research, would deny that majority of the hypotheses or experiments do fail and result in what we call as "negative data". Few of us would also accept rather confess that some of the negative data that they dealt with was important and may have otherwise resulted in revealing a new fact about an established theory, if was pursued further. However, owing to the fact that negative data do have less likelihood of being published and thus not helpful  for an early career scientist, almost all negative data are pre-destined to get buried in the volumes of laboratory notebooks, most often not to be read/looked at again even by a successor of that research group in future. Others in scientific fraternity besides few people working in the same group, do not generally have access to negative results, just because experimental outcomes that were not noteworthy or consistent enough to pass peer review and be published.

How could the availability of unpublished results be improved? I suggest an open-access journal for all research findings, which would let scientists submit their hypotheses and methodologies before an experiment, and their results afterwards, regardless of outcome. Yes, I am serious. However, such a journal or if I put it more practically, a database to accomodate all negative data would reveal how published studies fit into the larger set of conducted studies, and may help to answer many other unanswered questions that most of the scientific fraterny keeps wondering about.

A such database of unpublished findings will also address other shortcomings of the current scientific process, including the regular failure of scientists to report experiments, conditions or observations that are inconsistent with hypotheses; the addition or removal of participants and variables to generate statistical significance, and the probable existence of numerous published findings whose non-replicability is deemed mysterious because it is difficult and in many cases not worthwhile to spend your energy and time to report negative results.

There is a possibility that with availability of some such journal or database, people start finding some sort of trend rather a positive trend in series of negative data submitted by different unrelated group of investigators across the globe.  I can personally recall incidences while in informal gatherings, scientists especially those who are in early stage of their career, talking about their inability to replicate some established theories or findings and others approving that they had similar experience with replicating that so called "theory" or "finding". Most of them did not pursue it further, for the reasons described earlier. Now imagine a situation when someone disappointed from the negative results has ability to search through this "Journal of Unpublished Results" or "Unpublished Results: a Knowledge base" to see if there is a pattern in unpublished data.  I hope this is going to be extremely interesting if this could ever become possible.