Cancer research

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MD Anderson Cancer Center is ranked as one of the top cancer research institutions.

Cancer research is research into cancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure.[1]

Cancer research ranges from epidemiology, molecular bioscience to the performance of clinical trials to evaluate and compare applications of the various cancer treatments. 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 cancer immunotherapy and gene therapy.

History[edit]

Sidney Farber is regarded as the father of modern chemotherapy.

Cancer research has been ongoing for centuries. Early research focused on the causes of cancer.[2] Percivall Pott identified the first environmental trigger (chimney soot) for cancer in 1775 and cigarette smoking was identified as a cause of lung cancer in 1950. Early cancer treatment focused on improving surgical techniques for removing tumors. Radiation therapy took hold in the 1900s. Chemotherapeutics were developed and refined throughout the 20th century.[3]

The U.S. declared a "War on Cancer" in the 1970s, and increased the funding and support for cancer research.[4]

Types of research[edit]

Cancer research encompasses a variety of types and interdisciplinary areas of research. Scientists involved in cancer research may be trained in areas such as chemistry, biochemistry, molecular biology, physiology, medical physics, epidemiology, and biomedical engineering. Research performed on a foundational level is referred to as basic research and is intended to clarify scientific principles and mechanisms. Translational research aims to elucidate mechanisms of cancer development and progression and transform basic scientific findings into concepts that can be applicable to the treatment and prevention of cancer. Clinical research is devoted to the development of pharmaceuticals, surgical procedures, and medical technologies for the eventual treatment of patients.

Prevention and epidemiology[edit]

Cause and development of cancer[edit]

Early research on the cause of cancer was summarized by Haddow in 1958.[5] The first chemical carcinogen was identified in 1928-29 as 1:2-5:6-dibenzanthracene, and the carcinogeneic substance in pitch was identified as 3:4-benzopyrene in 1933. Haddow concluded that “there can be little doubt of the importance of their [chemical] combination with the genetical material” as the source of the chemical mechanism of action of carcinogens. Brookes and Lawley, in 1964, summarized ongoing research into the causes of cancer.[6] They referred to the competing hypotheses that carcinogens reacted mainly with proteins versus mainly with DNA. The direct research of Brookes and Lawley, testing carcinogenic hydrocarbons, indicated that they react with DNA. McCann et al.[7] in 1975 and McCann and Ames, in 1976,[8] tested 175 known carcinogens for interaction with DNA sufficient to cause mutations in their new Salmonella/microsome test. This test uses bacteria as sensitive indicators of DNA damage. They found that 90% of known carcinogens caused mutations in their test. They indicated that the carcinogens that did not cause mutations in their assay were likely due to the need for the carcinogens to be activated by enzymes not available in their system.

By 1981, Doll and Peto had conducted an epidemiological study in which they compared cancer rates for 37 specific cancers in the United States to rates for these cancers in populations where the incidence of these cancers is low.[9] The populations compared with US populations included Norwegians, Nigerians, Japanese, British, and Israeli Jews. Their conclusion was that 75 - 80% of the cases of cancer in the United States were likely avoidable. The avoidable sources of cancer included tobacco, alcohol, diet (especially meat and fat), food additives, occupational exposures (including aromatic amines, benzene, heavy metals, vinyl chloride), pollution, industrial products, medicines and medical procedures, UV light from the sun, exposure to medical x-rays, and infection. Many of these sources of cancer are DNA damaging agents.

More recent research, indicating both the role of DNA damage in causing cancer and other factors including reduced expression of DNA repair genes by epigenetic alterations (allowing DNA damages to accumulate) are summarized in Carcinogenesis and in an article by Bernstein et al. in 2013.[10]

Research into the cause of cancer 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 the aim to test safety and efficiency of the therapeutic intervention method. An important part of basic research is characterization of the potential 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.

Genes involved in cancer[edit]

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)."[11] 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.[12]

These large scale projects, involving about 350 different types of cancer, 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 suppressor 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.[13]

Detection[edit]

Prompt detection of cancer is important, since it is usually more difficult to treat in later stages. Accurate detection of cancer is also important because false positives can cause harm from unnecessary medical procedures. Some screening protocols are currently not accurate (such as prostate-specific antigen testing). Others such as a colonoscopy or mammogram are unpleasant and as a result some patients may opt out. Active research is underway to address all these problems.

One approach is blood screening for a wide variety of tumor markers.[14]

Research published in "Cell" suggests future cancer diagnostics to be accomplished at an early stage with a single drop of blood.[15]

Treatment[edit]

Emerging topics of cancer treatment research include:

Clinical trials[edit]

Research funding[edit]

Cancer research is funded by government grants, charitable foundations, and pharmaceutical and biotechnology companies.[20]

In the early 2000s, most funding for cancer research came from taxpayers and charities, rather than from corporations. In the US, less than 30% of all cancer research was funded by commercial researchers such as pharmaceutical companies.[21] Per capita, public spending on cancer research by taxpayers and charities in the US was five times as much in 2002-03 as public spending by taxpayers and charities in the 15 countries that were full members of the European Union.[21] As a percentage of GDP, the non-commercial funding of cancer research in the US was four times the amount dedicated to cancer research in Europe.[21] Half of Europe's non-commercial cancer research is funded by charitable organizations.[21]

Flaws and vulnerabilities[edit]

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.[22] Oncologist Paul Bunn, from the International Association for the Study of Lung Cancer[23] 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".[22] Fran Visco founder of the National Breast Cancer Coalition commented: "We cure cancer in animals all the time, but not in people."[22]

Cancer research processes have been criticised. These include, especially in the US, for the financial resources and positions required to conduct research. Other consequences of competition for research resources appear to be a substantial number of research publications whose results cannot be replicated. [24][25][26][27][28]

Public participation[edit]

One can share computer time for distributed cancer research projects like Help Conquer Cancer.[29] World Community Grid also had a project called Help Defeat Cancer. Other related projects include the Folding@home and Rosetta@home projects, which focus on groundbreaking protein folding and protein structure prediction research.

Members of the public can also join clinical trials as healthy control subjects or for methods of cancer detection.

Dominance of cancer research[edit]

Cancer Research has grown considerably as indicated by the number of records that have been indexed in the MEDLINE database, in the 1950s the proportion of cancer-related entries was approximately 6% of all entries and this has rose to 16% in 2016. [30] This rise may be attributed to the impact of scientific advances such as genomics, computing and mathematics, which have had a stronger influence in Cancer than in other areas such as Cardiovascular conditions.

Organizations[edit]

Breast cancer awareness ribbon statue in Kentucky

Organizations exist as associations for scientists participating in cancer research, such as the American Association for Cancer Research and American Society of Clinical Oncology, and as foundations for public awareness or raising funds for cancer research, such as Relay For Life and the American Cancer Society.

Awareness campaigns[edit]

Supporters of different types of cancer have adopted different colored awareness ribbons and promote months of the year as being dedicated to the support of specific types of cancer.[31] The American Cancer Society began promoting October as Breast Cancer Awareness Month in the United States in the 1980s. Pink products are sold to both generate awareness and raise money to be donated for research purposes. This has led to pinkwashing, or the selling of ordinary products turned pink as a promotion for the company.

See also[edit]

References[edit]

  1. ^ Birbrair, Alexander; Zhang, Tan; Wang, Zhong-Min; Messi, Maria Laura; Olson, John D.; Mintz, Akiva; Delbono, Osvaldo (2014-07-01). "Type-2 pericytes participate in normal and tumoral angiogenesis". American Journal of Physiology. Cell Physiology. 307 (1): C25–C38. doi:10.1152/ajpcell.00084.2014. ISSN 0363-6143. PMC 4080181Freely accessible. PMID 24788248. 
  2. ^ https://www.cancer.org/cancer/cancer-basics/history-of-cancer/cancer-causes-theories-throughout-history.html
  3. ^ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2927383/
  4. ^ https://dtp.cancer.gov/timeline/flash/milestones/M4_Nixon.htm
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  7. ^ McCann J, Choi E, Yamasaki E, Ames BN (1975). "Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals". Proc. Natl. Acad. Sci. U.S.A. 72 (12): 5135–9. doi:10.1073/pnas.72.12.5135. PMC 388891Freely accessible. PMID 1061098. 
  8. ^ McCann J, Ames BN (1976). "Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion". Proc. Natl. Acad. Sci. U.S.A. 73 (3): 950–4. doi:10.1073/pnas.73.3.950. PMC 336038Freely accessible. PMID 768988. 
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  13. ^ 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.
  14. ^ https://www.ted.com/talks/jorge_soto_the_future_of_early_cancer_detection?language=en
  15. ^ RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics Myron G. Best, Nik Sol, Irsan Kooi, Jihane Tannous, Bart A. Westerman, François Rustenburg, Pepijn Schellen, Heleen Verschueren, Edward Post, Jan Koster, Bauke Ylstra, Najim Ameziane, Josephine Dorsman, Egbert F. Smit, Henk M. Verheul, David P. Noske, Jaap C. Reijneveld, R. Jonas A. Nilsson, Bakhos A. Tannous12, Pieter Wesseling12, Thomas Wurdinger12correspondenceemail http://www.cell.com/cancer-cell/fulltext/S1535-6108(15)00349-9
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  23. ^ http://www.uchsc.edu/news/bridge/2003/October/bunnaslc.html
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  27. ^ Leaf, Clifton (2004-03-22). "Why We're Losing The War On Cancer". Fortune Magazine (CNN Money). 
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  30. ^ Reyes-Aldasoro C (2017). "The proportion of cancer-related entries in PubMed has increased considerably; is cancer truly "The Emperor of All Maladies"?". PLOS ONE. 12 (3): e0173671. doi:10.1371/journal.pone.0173671. PMC 5345838Freely accessible. PMID 28282418. 
  31. ^ https://www.cancer.net/research-and-advocacy/cancer-awareness-dates

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