Open Questions: Cancer

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Cancer is getting broken down into more and more separate diseases as we're able to subdivide the diagnostics and the genes associated with them, but we're starting to take a different view of viewing cancer as an overall disease, and we're looking at gene space where we think it can be targeted to deal with cancer as a whole.
J. Craig Venter

Introduction

Causes of cancer

Cellular biology of cancer

Stages of cancer

Natural defenses against cancer

Cancer therapies

Open questions

Recommended references: Web sites

Recommended references: Magazine/journal articles

Recommended references: Books

Introduction

Even though there is just one name, "cancer", it is sometimes helpful to think of the name as referring to a number of different diseases. Or, perhaps, if you wish, it may be useful to think of "cancer" as a type of disease, and there are a number of different varieties of the disease within the type.

In fact, there are about 200 anatomically different types of cancer. And if further distinctions are made based on the underlying molecular causes, it is estimated there may be 250,000 different types. Indeed, each individual case of cancer may arise through a slightly different sequence of cellular changes.

There are certainly many similarities among the diseases of this type. For example:

A cancer generally involves the unchecked and harmful proliferation of cells of a particular kind, such as cells in the skin, lungs, breast, or prostate gland.
This unchecked proliferation always results from damage to cellular DNA, which becomes unable to keep normal control over cell division.
Cells that have become cancerous usually cease to be able to perform their normal function in the body as a part of some specific organ type.
Cancer becomes fatal either when the organ where it occurs ceases to be able to perform its normal function, or when cancer cells "metastasize" and spread their uncontrolled proliferation to other parts of the body.

At the same time, it is helpful to regard different types of cancer as distinct diseases for various reasons:

There are a number of different reasons that cellular DNA can be damaged and hence lead to cancer. Different reasons usually apply to different types of cells. In other words, there are different causes for different types of cancer.
The best available treatment for a partiuclar type of cancer usually varies from one type to another, and depends on the specific way in which cellular DNA has been damaged, as well as on physiological differences between affected organs.
Different types of cancer vary greatly in their propensity to metastasize and hence in their degree of lethality.
The physiological effects of cancer in different organs vary greatly, and so lethality or other indirect effects can also vary greatly.

There are various ways to classify the different diseases which are types of cancer. The most common way, and perhaps the most useful to begin with, is simply by the part of the body or the organ which is affected.

Here is a table of the most common types of cancer, further broken down by estimated new cases and estimated deaths (in 2004), and even further by sex. (The percentages refer to relative frequency in a particular column.)

Cancer types
Estimated new cases Estimated deaths
Male Female Male Female
Prostate - 33% Breast - 32% Lung & bronchus - 32% Lung & bronchus - 25%
Lung & bronchus - 13% Lung & bronchus - 12% Prostate - 10% Breast - 15%
Colon & rectum - 11% Colon & rectum - 11% Colon & rectum - 10% Colon & rectum - 10%
Urinary bladder - 6% Uterine corpus - 6% Pancreas - 5% Ovary - 6%
Melanoma - 4% Ovary - 4% Leukemia - 5% Pancreas - 6%
Non-Hodgkin lymphoma - 4% Non-Hodgkin lymphoma - 4% Non-Hodgkin lymphoma - 4% Leukemia - 4%
Kidney - 3% Melanoma - 4% Esophagus - 4% Non-Hodgkin lymphoma - 3%
Leukemia - 3% Thyroid - 3% Liver - 3% Uterine corpus - 3%
Oral caviity - 3% Pancreas - 2% Urinary bladder - 3% Multiple myeloma - 2%
Pancreas - 2% Urinary bladder - 2% Kidney - 3% Brain - 2%
All other - 18% All other - 20% All other - 21% All other - 24%
Source: American Cancer Society - Cancer Statistics Presentation 2004

Cancer types
Estimated new cases	Estimated deaths
Male	Female	Male	Female
Prostate - 33%	Breast - 32%	Lung & bronchus - 32%	Lung & bronchus - 25%
Lung & bronchus - 13%	Lung & bronchus - 12%	Prostate - 10%	Breast - 15%
Colon & rectum - 11%	Colon & rectum - 11%	Colon & rectum - 10%	Colon & rectum - 10%
Urinary bladder - 6%	Uterine corpus - 6%	Pancreas - 5%	Ovary - 6%
Melanoma - 4%	Ovary - 4%	Leukemia - 5%	Pancreas - 6%
Non-Hodgkin lymphoma - 4%	Non-Hodgkin lymphoma - 4%	Non-Hodgkin lymphoma - 4%	Leukemia - 4%
Kidney - 3%	Melanoma - 4%	Esophagus - 4%	Non-Hodgkin lymphoma - 3%
Leukemia - 3%	Thyroid - 3%	Liver - 3%	Uterine corpus - 3%
Oral caviity - 3%	Pancreas - 2%	Urinary bladder - 3%	Multiple myeloma - 2%
Pancreas - 2%	Urinary bladder - 2%	Kidney - 3%	Brain - 2%
All other - 18%	All other - 20%	All other - 21%	All other - 24%
Source: American Cancer Society - Cancer Statistics Presentation 2004

Causes of cancer:

Ionizing radiation
UV radiation
Genetic predispositions (oncogenes)
Free radicals
Environmental/dietary carcinogens
Errors in DNA replication
(Onco)viruses, e. g. Rous sarcoma, HBV, HPV
Bacteria (H. pylori)

Open questions

What makes environmental and dietary substances carcinogenic?
At what points in the development of a cancer is the process most easily interrupted?
How do very large animals like elephants and whales avoid cancer?
Are there blood tests which can detect cancer at an early stage?
What is the role of the immune system in dealing with cancer?
Why is it so hard to develop therapeutic drugs to treat cancer, even though we know so much about the signaling pathways that facilitate cancer?

Recommended references: Web sites

Site indexes

Open Directory Project: Cancer: Categorized and annotated links. A version of this list is at Google, with entries sorted in "page rank" order. May also be found at Netscape.
Galaxy: Cancer: Categorized site directory. Entries usually include descriptive annotations.

Sites with general resources

MedlinePlus: Cancers Topics: MelinePlus provides links to many types of information on almost every medical topic -- news, overviews, symptoms and diagnosis, genetics, research, etc. This page gives links to pages on specific types of cancer.
OncoLink: A general portal for cancer-related information. Many links are classified by types of cancer. Other features include news, discussion forums, FAQs, and other services for patients and medical specialists.
National Cancer Institute: This U. S. government site provides a huge mine of resources on cancer, including many overview articles, fact sheets, recent news, information on clinical trials, and general cancer information.
Plans and Priorities for Cancer Research: This is the budget proposal of the U. S. National Cancer Institute for 2004. It has special emphasis on important areas of cancer research. Similar but more recent information can be found in the budget proposals for 2005, 2006, and 2007.
New Scientist Special Report on Cancer: Primarily offers links to many news articles from the past several years of New Scientist magazine. But there are also other features, including facts and figures, external links, frequently-asked questions, and a short bibliography.
Nature Cancer Update: Excellent portal/gateway for cancer research. Provides general and specialist news on cancer research, and other services for professionals.
BioOncology OnLine: "The Web resource for biologic oncology". Sponsored by Genentech.
Compute Against Cancer: Cooperative distributed computing project to assist in cancer research.
Intel-United Devices Cancer Research Project: Another Cooperative distributed computing project to assist in cancer research.
The Cancer Genome Atlas: Web site of TCGA project of the U. S. National Cancer Institue. "The Cancer Genome Atlas (TCGA) is a comprehensive and coordinated effort to accelerate our understanding of the molecular basis of cancer through the application of genome analysis technologies, including large-scale genome sequencing."
The Cancer Genome Project: "The Cancer Genome Project is using the human genome sequence and high throughput mutation detection techniques to identify somatically acquired sequence variants/mutations and hence identify genes critical in the development of human cancers." Web site includes news, external links, lists of publications, and databases of accumulated data, such as the Cancer Gene Census, Catalog of Somatic Mutations in Cancer (COSMIC), and the CGP Copy Number Analysis.
Cancer Prevention and Control: Site maintained by the U. S. Centers for Disease Control and Prevention. Provides information on different types of cancer, fact sheets, and some scientific articles.
Cancer Research UK - Science and Research: Web pages of a UK organization that helps coordinate and fund cancer research, part of the Cancer Research UK site.
National Toxicology Program Report on Carcinogens: This is the U. S. government's official list of known carcinogens. See in particular the 10th Report on Carcinogens, which lists details of 228 substances "known" or "reasonably anticipated" to pose a cancer risk. (Individual sections are in PDF format.)
American Institute for Cancer Research: Home page of an organization which "supports research into the role of diet and nutrition in the prevention and treatment of cancer". It advocates a predominantly plant-based diet and consuming more vegetables, fruits, whole grains and beans. Further explanation of this position is provided in the section of general information on diet & cancer.
Memorial Sloan-Kettering Cancer Center: Web site of a major cancer research and treatment center. The site provides extensive information on all types of cancer, genetics of cancer, and cancer risk reduction.
The Oral Cancer Foundation: "The Oral Cancer Foundation is a national public service, non-profit entity designed to reduce suffering and save lives through prevention, education, research, advocacy, and support." The site contains a lot of information pertaining to oral and other cancers, especially here.

Surveys, overviews, tutorials

Category: Oncology: Topic category from Wikipedia.
Cancer: Article from Wikipedia. See also Oncology.
Cancer (ClearlyExplained.com): Overview in several parts by Richard Conan-Davies.
Understanding Cancer Series: A series of tutorials in slide format on topics related to cancer, such as cancer genomics, molecular diagnostics, and angiogenesis
Can you catch cancer?: January 2006 article at Guardian Unlimited about types of infections that can cause cancer.
Biology of Cancer: A ScienceWeek "symposium" consisting of excerpts and summaries of articles from various sources.
Cancer Medicine: Complete online textbook. Index. Part of the NCBI Bookshelf.
Cancer Death -- Causes & Prevention: Detailed survey by Ben Best.
Cancer: diet and physical activity's impact: An informative article published by the World Health Organization.
Lung Cancer: December 2006 Scientific American Sidebar about the experimental lung cancer vaccine Stimuvax.
Leafy Letdown: April 2005 Scientific American In Focus article, subtitled "Eating vegetables seems to do little in warding off cancer."
New Light on Breast Cancer: August 2002 Scientific American In Focus article, subtitled "Laser light and thermal heat could help improve the accuracy of mammograms"
Breast Cancer: Knocking Out a Killer: June 2001 Scientific American In Focus article, subtitled "Test-tube studies have uncovered key facts about the breast cancer gene BRCA1, but new animal models of the disease promise to reveal much more."
Cancer in the Crosshairs: Brief September 2001 Scientific American article about the new cancer drug Gleevec.
Solid Proof of Immunity against Cancer: April 2001 Scientific American news article about how the immune system can prevent tumor formation.
A New Skin Cancer Culprit: February 2001 Scientific American news article about a mutation implicated in squamous cell carcinoma.
New Target for Melanoma Treatment?: January 2001 Scientific American news story about a new gene found to be involved in the resistance of melanoma to chemotherapy.
Clue to Cancer in Cell-Death Proteins: October 2000 Scientific American news article about proteins involved with apoptosis of T cells.

Recommended references: Magazine/journal articles

A Malignant Flame
Gary Stix
Scientific American, July 2007
Chemo Control
Jeneen Interlandi
Scientific American, April 2007

Mapping the Cancer Genome
Francis S. Collins; Anna D. Barker
Scientific American, March 2007
Stem Cells: The Real Culprits in Cancer?
Michael F. Clarke; Michael W. Becker
Scientific American, July 2006
Tumor-Busting Viruses
Dirk M. Nettelbeck; David T. Curiel
Scientific American, October 2003: There is a sidebar: Targeting Melanoma
Untangling the Roots of Cancer
W. Wayt Gibbs
Scientific American, July 2003
T Cell Triumph
Diane Martindale
Scientific American, February 2003
DNA Chips Target Cancer
Marc Wortman
Technology Review, July/August 2001, pp. 50-55: By enabling the rapid identification of all of the many types of genes that may be expressed in cancerous cells, DNA microarrays should soon make diagnosis of cancer much more rapid and accurate. The same chips also play an important role in identification and testing of effective cancer drugs.
Understanding Cancer's Spread
Damaris Christensen
Science News, June 2, 2001, pp. 350-351: Discovering the mechanisms of cellular movement and growth is a key step to developing successful cancer therapies.
[References]
DNA Vaccines as Cancer Treatment
Edward P. Cohen, Edwin F. de Zoeten, Morton Schatzman
American Scientist, July-August 1999, pp. 328-335: "No longer limited to warding against infectious agents, vaccines may help treat diseases after they have been diagnosed."
Metastasis
Cornelis J. F. VanNoorden, Linda C. Meade-Tollin, Fred T. Bosman
American Scientist, March-April 1998, pp. 130-141: Metastasis of cancer cells represents a major malfunction of the normal cell life cycle. Genetic abnormalities play a significant role.
How Cancer Arises
Robert A. Weinberg
Scientific American, September 1996, pp. 62-70: Distinctive chemical and genetic differences of cancer cells from normal cells have been identified.
How Cancer Spreads
Erkki Ruoslahti
Scientific American, September 1996, pp. 72-77: Various control mechanisms prevent normal cells from surviving anywhere other than where they "belong". Cancers metastasize by evading these controls.
Immunotherapy for Cancer
Lloyd J. Old
Scientific American, September 1996, pp. 136-143: Rapidly increasing knowledge of how the immune system works should lead to a variety of possible treatments for cancer. Among the more promising are vaccines that stimulate the immune system and monoclonal antibodies which can deliver toxic agents specifically to cancer cells.
New Molecular Targets for Cancer Therapy
Allen Oliff; Jackson B. Gibbs; Frank McCormick
Scientific American, September 1996, pp. 144-149: Cancer cells are characterized by specific DNA mutations which either produce a tendency to excessive proliferation or else disable mechanisms that resist this proliferation. Drugs that target such mutations specifically are therapeutically promising.
Fighting Cancer by Attacking Its Blood Supply
Judah Folkman
Scientific American, September 1996, pp. 150-154: Solid tumors such as occur in most forms of cancer consist of masses of cells which require a blood supply in order to grow. Cancer cells have mutations which allow them to turn on the development of capillaries to supply the needed blood. Drugs that inhibit this process of angiogenesis should be useful in treating cancers of this sort.
Sunlight and Skin Cancer
David J. Leffell; Douglas E. Brash
Scientific American, July 1996, pp. 52-59: The mechanism by which the ultraviolet component of sunlight induces skin cancer is a good example of carcinogenesis in general. The ultraviolet light causes a mutation in the p53 tumor-suppressor gene and also causes premature death of other cells which leads to selective favoring of cells with already damaged DNA.
Taxoids: New Weapons against Cancer
Nicolaou, Guy, Potier
Scientific American, June 1996: Taxol, a natural substance originally extracted from the bark of yew trees, was found to be very effective as a treatment for ovarian cancer. It can now be manufactured semisynthetically and appears to be very effective also with breast cancer, lung cancer, and melanoma.
Uncovering New Clues to Cancer Risk
Frederica P. Perera
Scientific American, May 1996, pp. 54-62: Now that we know much more about the molecular and cellular mechanisms by which cancer develops, we can use sensitive tests to detect risk factors like exposure to carcinogens or genetic defects. This new discipline is known as molecular epidemology.
Telomeres, Telomerase and Cancer
Carol W. Greider, Elizabeth H. Blackburn
Scientific American, February 1996, pp. 92-97: Chromosomal features known as telomeres seem to govern cell division in normal cells. The enzyme telomerase plays a fundamental role in the function of telomeres.
The Genetic Basis of Cancer
Webster K. Cavenee; Raymond L. White
Scientific American, March 1995, pp. 72-79: Two types of genetic defects contribute to the development of cancer -- defects that encourage cell proliferation and defects that weaken the inhibition of uncontrolled proliferation. An accumulation of such defects in a single cell must occur before cancerous growth commences.

Recommended references: Books

Mel Greaves -- Cancer: The Evolutionary Legacy
Oxford University Press, 2000: Greaves is a professor of cell biology and director of a major cancer research center. His book tackles the seemingly intractable question of what "causes" cancer, which has eluded any simple answer in terms of infection, genetic factors, or the like. The author proposes to apply new insights from evolutionary theory to the understanding of cancer. The book is relatively brief, yet it manages to deal very clearly with the nature of cancer, the etiology of the main types of cancer, and prospects for reducing the incidence of cancer and finding ways to treat it. This is highly recommended, and is one of the finest books around about any topic in science.
Gary D. Kruh; Kenneth D. Tew, eds. – Basic Science of Cancer
Current Medicine, 2000: This is not an easy volume to find, and it's intended for medical professionals. But scientifically-minded readers who peruse the 13 separately-authored papers in the book will be rewarded with at least a general understanding of the plethora of factors that subvert normal cell biology to produce a cancer cell. Readers should come equipped with a working knowledge of molecular cell biology, but need not memorize all the biochemical details presented here, if they aren't studying for an exam.
Robert A. Weinberg -- One Renegade Cell: How Cancer Begins
Basic Books, 1998: Weinberg is directory of the Oncology Research Laboratory at the Whitehead Institute, where much of the most significant research on cancer has been done. His book is relatively brief, yet covers most of the factors that are known to play a role in a cell's becoming cancerous. In brief, cancer results from mutations in cellular DNA which either lead to uncontrolled cell division or the failure to limit such division. Other factors which contribute to the metastasis of cancer are also discussesd.

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