Cancer research

This article is about research into cancer, in general. For the UK-based charity, see Cancer Research UK. For the journal, see Cancer Research (journal).

University of Florida Cancer Hospital

Cancer research is basic research into cancer in order to identify causes and develop strategies for prevention, diagnosis, treatments and cure.

Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate and compare applications of the various cancer treatment. These applications include surgery, radiation therapy, chemotherapy, hormone therapy, Immunotherapy and combined treatment modalities such as chemo-radiotherapy. Starting in the mid-1990s, the emphasis in clinical cancer research shifted towards therapies derived from biotechnology research, such as immunotherapy and gene therapy.

Areas of research

Cause

This type of research involves many different disciplines including genetics, diet, environmental factors (i.e. chemical carcinogens). In regard to investigation of causes and potential targets for therapy, the route used starts with data obtained from clinical observations, enters basic research, and, once convincing and independently confirmed results are obtained, proceeds with clinical research, involving appropriately designed trials on consenting human subjects, with aim to test safety and efficiency of the therapeutic intervention method. Important part of basic research is characterization of the potential function of mechanisms of carcinogenesis, in regard to the types of genetic and epigenetic changes that are associated with cancer development. The mouse is often used as a mammalian model for manipulation of the function of genes that play a role in tumor formation, while basic aspects of tumor initiation, such as mutagenesis, are assayed on cultures of bacteria and mammalian cells.

Important cell types involved in cancer growth

There are several different cell types that are critical to tumour growth. In particular Endothelial Progenitor Cells are a very important cell population in tumour blood vessel growth. This finding was demonstrated in the high impact factor journals of Science (2008) and Genes and Development (2007)which also showed that Endothelial Progenitor Cells are critical for metastasis and the angiogenesis.^[1][2] This importance of endothelial progenitor cells in tumour growth and angiogenesis has been confirmed by a recent publication in Cancer Research (August 2010). This seminal paper has demonstrated that endothelial progenitor cells can be marked using the Inhibitor of DNA Binding 1 (ID1). This novel finding meant that investigators were able to track endothelial progenitor cells from the bone marrow to the blood to the tumour-stroma and even incorporated in tumour vasculature. This finding of endothelial progenitor cells incorporated in tumour vasculature proves the importance of this cell type in blood vessel development in a tumour setting. Furthermore, ablation of the endothelial progenitor cells in the bone marrow lead to a significant decrease in tumour growth and vasculature development. Therefore endothelial progenitor cells are very important in tumour biology and present novel therapeutic targets.^[3]

Oncogenomics/Genes involved in cancer

Main article: Oncogenomics

See also: Databases for oncogenomic research

The goal of oncogenomics is to identify new oncogenes or tumor suppressor genes that may provide new insights into cancer diagnosis, predicting clinical outcome of cancers, and new targets for cancer therapies. As the Cancer Genome Project stated in a 2004 review article, "a central aim of cancer research has been to identify the mutated genes that are causally implicated in oncogenesis (cancer genes)."^[4] The Cancer Genome Atlas project is a related effort investigating the genomic changes associated with cancer, while the COSMIC cancer database documents acquired genetic mutations from hundreds of thousands of human cancer samples.^[5]

These large scale projects, involving about 350 different types of tumour, have identified ~130,000 mutations in ~3000 genes that have been mutated in the tumours. The majority occurred in 319 genes of which 286 were tumour supressor genes and 33 oncogenes.

Several hereditary factors can increase the chance of cancer-causing mutations, including the activation of oncogenes or the inhibition of tumor suppressor genes. The functions of various onco- and tumor suppressor genes can be disrupted at different stages of tumor progression. Mutations in such genes can be used to classify the malignancy of a tumor.

In later stages, tumors can develop a resistance to cancer treatment. The identification of oncogenes and tumor suppressor genes is important to understand tumor progression and treatment success. The role of a given gene in cancer progression may vary tremendously, depending on the stage and type of cancer involved.^[6]

Genes and protein products that have been identified by at least two independent publications as being involved in cancer are:^[4]
ABI1, ABL2, ACSL6, AF1Q, AF5Q31 (also known as MCEF), AKT1, ARNT, ASPSCR1, ATF1, ATIC, BCL10, BFHD, BIRC3, BMPR1A, BTG1, CBFA2T1, CBFA2T3, CBFB, CCND1, CDC2, CDK4, CHIC2, CHN1, COPEB, COX6C, CTNNB1, CYLD, DDB2, DDIT3, DEK, Eif4a, EIF4A2, EPS15, ERCC2, ERCC3, ERCC5, ERG, ETV4, ETV6, EWSR1, EXT1, EXT2, FANCC, FANCG, FGFR1OP, FGFR3, FH, FIP1L1, FUS, GAS7, GATA1, GMPS, GOLGA5, GPC (gene), GPHN, HIST1H4I, HRAS, HSPCA, IL21R, IIRF4, KRAS2, LASP1, LCP1, LHFP, LMO2, LYL1, MADH4, MEIS1, MLF1, MLH1, MLLT3, MLLT6, MNAT1, MSF, MSH2, MSN, MUTYH, MYC, NCOA4, NF2, NPM1, NRAS, PAX8, PCBD, PDGFB, PHOX2B, PIM1, PLK2, PNUTL1, POU2F1, PPARG, PRCC, PRKACB, PRKAR1A, PTEN, PTPN11, RABEP1, RAD51L1, RAP1GDS1, RARA, RB1, RET, RHOH, RPL22, SBDS, SDHB, SEPTIN6, SET, SH3GL1, SS18L1, SSX1, SSX2, SSX4, STAT3, TAF15, TCF12, TCL1A, TFE3, TFEB, TFG, TFPT, TFRC, TNFRSF6, TP53, TPM3, TPM4, TRIP11, VHL, WAS, WT1, ZNF198, ZNF278, ZNF384, ZNFN1A1

Treatment

Main article: Cancer#Treatment

Current topics of cancer treatment research include:

• Boosting the immune system
• Anti-cancer vaccine — based on exposing some cancer cells extracted from a tumour to UV rays for 24 hrs then injecting them back into the organism, this approach has already been successful on rats.
• Chemotherapy
• Gene therapy^[7]
• Photodynamic therapy
• Radiation therapy
• Reoviridae (Reolysin drug therapy)
• Targeted therapy

Specific treatment research topics

Dichloroacetate

In January 2007 researchers of the University of Alberta reported preliminary results of dichloroacetate (DCA) causing regression in several cancers in vitro, including lung, breast and brain tumors.^[8] Since the compound DCA itself cannot be patented it could be an inexpensive alternative to other treatments, depending of course on whether the method of using DCA in the treatment of cancer is patentable. Clinical use of DCA will require further public/private investment for clinical trials.^[9] The initial research was funded by the Canadian Institutes of Health Research.^[10]

Vaccines

• HBV hepatitis "B" virus which leads to liver cancer.
• HPV vaccine human papillovirus HPV-16, HPV-18 for cervical cancer, genital warts, anal, vulvar, vaginal, penile, and HPV oral cancers.
• Canine Melanoma Vaccine^[11]
• Oncophage^[12]

Other methods

• Some research may indicate a connection between Vitamin D deficiency and cancer.^[13]

Issues

Newsweek magazine published an article criticising the use of lab rats on cancer research because even though researchers frequently manage to cure lab mice transplanted with human tumors, few of those achievements are relevant to humanity.^[14] Oncologist Paul Bunn, from the International Association for the Study of Lung Cancer^[15] said: "We put a human tumor under the mouse's skin, and that microenvironment doesn't reflect a person's—the blood vessels, inflammatory cells or cells of the immune system".^[14] Fran Visco founder of the National Breast Cancer Coalition completed:"We cure cancer in animals all the time, but not in people."^[14]

Funding

Some methods, like Dichloroacetate^[9] and Coley's Toxins, cannot be patented and thus would not garner the investment interest towards research from the pharmaceutical industry. Many claim that this is why such research is often slow moving, as it lacks funding from pharmaceutical companies.

Innovation

The organizational behavior of the large institutions and corporations that research cancer, may unduly favor low-risk research into small incremental advancements, over innovative research that might discover radically new and dramatically improved therapy.^[16][17] Breakthrough-ideas are frequently scoffed at by the powers that be.^[18]

Distributed computing

One can share computer time for distributed cancer research projects like Help Conquer Cancer.^[19] World Community Grid also had a project called Help Defeat Cancer. Other related projects include the Folding@Home and Rosetta@home projects.

Organizations

• Cancer organizations
• American Association for Cancer Research
• American Brain Tumor Association
• American Society of Clinical Oncology
• Australian Cancer Research Foundation
• Bath Cancer Research Unit
• Brain Tumor Foundation of Canada
• Brain Tumor Funders' Collaborative
• CACA
• Canadian Cancer Society
• Cancer Research
• Cancer Research Foundation
• Cancer Research Institute, Inc.
• Cancer Research UK
• Childhood Cancer Research Group
• Damon Runyon Cancer Research Foundation
• Dana-Farber/Harvard Cancer Center
• E-Foundation for Cancer Research
• Friends of Cancer Research
• Gateway for Cancer Research
• German Cancer Research Center
• Grassroots Cancer Research Foundation
• Institute of Cancer Research
• International Agency for Research on Cancer
• International Cancer Genome Consortium
• Israel Cancer Research Fund
• James S. McDonnell Foundation
• Joe Andruzzi Foundation
• Lance Armstrong Foundation
• Ludwig Institute for Cancer Research
• Memorial Sloan-Kettering Cancer Center
• National Brain Tumor Society
• National Cancer Institute
• National Foundation for Cancer Research
• National Institute of Health
• NCI-designated Cancer Center
• Northern California Cancer Center
• Save A Brain Foundation
• Terry Fox Foundation
• TGen Drug Development (TD2)
• TGen
• Tower Cancer Research Foundation
• United Devices Cancer Research Project
• University of Florida Cancer Hospital
• USCACA
• Walker Cancer Research Institute

See also

• Alternative cancer treatment
• Anticancer Research (journal)
• Atlas of Genetics and Cytogenetics in Oncology and Haematology
• Cancer epidemiology
• Clinical trial
• Cooperative Human Tissue Network (CHTN)
• List of pharmaceutical companies
• Oncology

References

1. ^ Gao D et al. (2008). "Endothelial Progenitor Cells Control the Angiogenic Switch in Mouse Lung Metastasis". Science 319 (5860): 195–198. doi:10.1126/science.1150224. PMID 18187653. 
2. ^ Nolan DJ et al. (2007). "Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization". Genes and Development 21 (12): 1546–1558. doi:10.1101/gad.436307. PMC 1891431. PMID 17575055. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1891431. 
3. ^ Mellick As, Plummer PN et al. (2010). "Using the Transcription Factor Inhibitor of DNA Binding 1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumor Angiogenesis and Growth". Cancer Research 70 (18): 7273–7282. doi:10.1158/0008-5472.CAN-10-1142. PMC 3058751. PMID 20807818. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3058751. 
4. ^ ^{a b} Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, Rahman N, Stratton MR (2004). "A census of human cancer genes". Nat. Rev. Cancer 4 (3): 177–83. doi:10.1038/nrc1299. PMC 2665285. PMID 14993899. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2665285. 
5. ^ Forbes S, Clements J, Dawson E, Bamford S, Webb T, Dogan A, Flanagan A, Teague J, Wooster R, Futreal PA, Stratton MR (2006). "COSMIC 2005". Br J Cancer 94 (2): 318–22. doi:10.1038/sj.bjc.6602928. PMC 2361125. PMID 16421597. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2361125. 
6. ^ Vlahopoulos SA, Logotheti S, Mikas D, Giarika A, Gorgoulis V, Zoumpourlis V.The role of ATF-2 in oncogenesis.Bioessays. 2008 Apr;30(4):314-27.
7. ^ "Gene Therapy, Cancer-Killing Viruses And New Drugs Highlight Novel Approaches To Cancer Treatment". Medical News Today. http://www.medicalnewstoday.com/medicalnews.php?newsid=68204. Retrieved April 24, 2007. 
8. ^ Alberta scientists test chemotherapy alternative. Last Updated Wednesday, January 17, 2007
9. ^ ^{a b} "Cheap, safe drug kills most cancers". New Scientist. 2007-01-17. http://www.newscientist.com/article.ns?id=dn10971. Retrieved 2007-01-17. 
10. ^ University of Alberta - Small molecule offers big hope against cancer. January 16, 2007
11. ^ Liao JC, Gregor P, Wolchok JD, Orlandi F, Craft D, Leung C, Houghton AN, Bergman PJ. (2006). "Vaccination with human tyrosinase DNA induces antibody responses in dogs with advanced melanoma". Cancer Immun. 6: 8. PMC 1976276. PMID 16626110. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1976276. 
12. ^ http://www.antigenics.com/product/oncophage.shtml
13. ^ "Vitamin D casts cancer prevention in new light". Globe and Mail. 2007-04-28. http://www.theglobeandmail.com/servlet/story/RTGAM.20070428.wxvitamin28/BNStory/specialScienceandHealth/home. Retrieved 2007-04-29. 
14. ^ ^{a b c} http://www.newsweek.com/id/157548/page/3
15. ^ http://www.uchsc.edu/news/bridge/2003/October/bunnaslc.html
16. ^ Kolata, Gina (April 23, 2009). "Advances Elusive in the Drive to Cure Cancer". The New York Times. http://www.nytimes.com/2009/04/24/health/policy/24cancer.html. Retrieved 2009-12-29. 
17. ^ Kolata, Gina (June 27, 2009). "Grant System Leads Cancer Researchers to Play It Safe". The New York Times. http://www.nytimes.com/2009/06/28/health/research/28cancer.html. Retrieved 2009-12-29. 
18. ^ Kolata, Gina (December 29, 2009). "Old Ideas Spur New Approaches in Cancer Fight". The New York Times. http://www.nytimes.com/2009/12/29/health/research/29cancer.html. Retrieved 2009-12-29. 
19. ^ "Help Conquer Cancer". 2007-11-19. http://www.worldcommunitygrid.org/projects_showcase/hcc1/viewHcc1Main.do. Retrieved 2007-11-19. 

External links

• A list of Cancer Therapeutic Targets at Sino Biological
• Cancer Genome Anatomy Project @ The NIH
• Cancer Research Genetics
• Cancer Research Jobs
• CBC Digital Archives – Cancer Research: The Canadian Quest for a Cure
• Kolata, Gina. "Forty Years’ War". The New York Times. http://nytimes.com/40years. Retrieved 2009-12-29.  "Articles in this series... examine the struggle to defeat cancer."
• Dana-Farber/Harvard Cancer Center
• Is the cure for cancer a virus? at HowStuffWorks
• Stanford's Institute for Stem Cell Biology and Regenerative Medicine
• The Integrative Cancer Biology Program @ National Cancer Institute