Cancer research is research intocancer to identify causes and develop strategies for prevention, diagnosis, treatment, and cure.
Cancer research ranges from epidemiology, molecular bioscience to the performance ofclinical 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 frombiotechnology research, such ascancer immunotherapy andgene therapy.
Cancer research is done in academia, research institutes, and corporate environments, and is largely government funded.[citation needed]
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.[1]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.
The U.S. declared a "War on Cancer" in the 1970s, and increased the funding and support for cancer research.[2]
Some of the most highly cited and most influential research reports include:
The Hallmarks of Cancer, published in 2000, andHallmarks of Cancer: The Next Generation, published in 2011, byDouglas Hanahan andRobert Weinberg. Together, these articles have been cited in over 30,000 published papers.
Cancer research encompasses a variety of types and interdisciplinary areas of research. Scientists involved in cancer research may be trained in areas such aschemistry,biochemistry,molecular biology,physiology,medical physics,epidemiology, andbiomedical engineering. Research performed on a foundational level is referred to asbasic 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.
However, one 2015 study suggested that between ~70% and ~90% of cancers are due to environmental factors and therefore potentially preventable.[5][contradictory] Furthermore, it is estimated that with further research cancer death rates could be reduced by 70% around the world even without the development of any new therapies.[3] Cancer prevention research receives only 2–9% of global cancer research funding,[3] albeit many of the options for prevention are already well-known without further cancer-specific research but are not reflected in economics and policy.Mutational signatures of various cancers, for example, could reveal further causes of cancer and support causal attribution.[6][additional citation(s) needed]
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 asprostate-specific antigen testing). Others such as acolonoscopy ormammogram are unpleasant and as a result some patients may opt out. Active research is underway to address all these problems, to develop novel ways of cancer screening and to increase detection rates.[citation needed][further explanation needed]
Numerouscell signaling pathways are disrupted in the development of cancer.
Research into the cause of cancer involves many different disciplines including genetics, diet, environmental factors (i.e. chemicalcarcinogens). 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.
The goal ofoncogenomics is to identify newoncogenes ortumor suppressor genes that may provide new insights into cancer diagnosis, predicting clinical outcome of cancers, and new targets for cancer therapies. As theCancer 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)."[32]The Cancer Genome Atlas project is a related effort investigating the genomic changes associated with cancer, while theCOSMIC cancer database documents acquired geneticmutations from hundreds of thousands of human cancer samples.[33]
These large scale projects, involving about 350 different types of cancer, have identified ~130,000mutations in ~3000genes that have been mutated in the tumors. The majority occurred in 319 genes, of which 286 were tumor 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.[34]
Cancer epigenetics is the study ofepigenetic modifications to theDNA ofcancer cells that do not involve a change in the nucleotide sequence, but instead involve a change in the way the genetic code is expressed. Epigenetic mechanisms are necessary to maintain normal sequences of tissue specific gene expression and are crucial for normal development.[35] They may be just as important, if not even more important, thangenetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss ofexpression of genes that occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation ofCpG islands) than by mutations. As Vogelstein et al. points out, in a colorectal cancer there are usually about 3 to 6 driver mutations and 33 to 66hitchhiker or passenger mutations.[36] However, in colon tumors compared to adjacent normal-appearing colonic mucosa, there are about 600 to 800 heavily methylated CpG islands in the promoters of genes in the tumors while these CpG islands are not methylated in the adjacent mucosa.[37][38][39] Manipulation of epigenetic alterations holds great promise for cancer prevention, detection, and therapy.[40][41] In different types of cancer, a variety of epigenetic mechanisms can be perturbed, such as the silencing oftumor suppressor genes andactivation ofoncogenes by alteredCpG islandmethylation patterns,histone modifications, and dysregulation ofDNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.
Advertisement suggesting that a healthy diet helps prevent cancer.
Many dietary recommendations have been proposed to reduce the risk of cancer, few have significant supporting scientific evidence.[42][43][44]Obesity anddrinking alcohol have been correlated with the incidence and progression of some cancers.[42] Lowering the consumption ofsweetened beverages is recommended as a measure to address obesity.[45]
Dietary recommendations for cancer prevention typically includeweight management and eating ahealthy diet, consisting mainly of "vegetables, fruit, whole grains and fish, and a reduced intake of red meat, animal fat, and refined sugar."[42] A healthy dietary pattern may lower cancer risk by 10–20%.[53] There is no clinical evidence that diets or specific foods can cure cancer.[54][55]
Cancer research is funded bygovernment grants, charitable foundations and pharmaceutical and biotechnology companies.[74]
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.[75] 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.[75] 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.[75] Half of Europe's non-commercial cancer research is funded by charitable organizations.[75]
TheNational Cancer Institute is the major funding institution in the United States. In the 2023 fiscal year, the NCI funded $7.1 billion in cancer research.[76]
Difficulties inherent to cancer research are shared with many types ofbiomedical research.
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 bereplicated.[77][78][79][80]
Results from The Reproducibility Project: Cancer Biology suggest most studies of the cancer research sector may not be replicable.In a 2012 paper,C. Glenn Begley, a biotech consultant working atAmgen, and Lee Ellis, a medical researcher at the University of Texas, found that only 11% of 53 pre-clinical cancer studies had replications that could confirm conclusions from the original studies.[81] In late 2021, The Reproducibility Project: Cancer Biology examined 53 top papers about cancer published between 2010 and 2012 and showed that among studies that provided sufficient information to be redone, the effect sizes were 85% smaller on average than the original findings.[82][83] A survey of cancer researchers found that half of them had been unable to reproduce a published result.[84] Another report estimated that almost half of randomized controlled trials contained flawed data (based on the analysis of anonymized individual participant data (IPD) from more than 150 trials).[85]
MatchMiner overview of data flow and modes of use[87]
Members of the public can also joinclinical trials as healthy control subjects or for methods of cancer detection.
There could be software and data-related procedures that increase participation in trials and make them faster and less expensive. Oneopen source platform matches genomically profiled cancer patients toprecision medicine drug trials.[88][87]
Supporters of different types of cancer have adopted different coloredawareness ribbons and promote months of the year as being dedicated to the support of specific types of cancer.[89] The American Cancer Society began promoting October asBreast 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 topinkwashing, or the selling of ordinary products turned pink as a promotion for the company.
^di Pietro A, Tosti G, Ferrucci PF, Testori A (December 2008). "Oncophage: step to the future for vaccine therapy in melanoma".Expert Opinion on Biological Therapy.8 (12):1973–84.doi:10.1517/14712590802517970.PMID18990084.S2CID83589014.
^Kishore, Chandra; Bhadra, Priyanka (July 2021). "Targeting Brain Cancer Cells by Nanorobot, a Promising Nanovehicle: New Challenges and Future Perspectives".CNS & Neurological Disorders Drug Targets.20 (6):531–9.doi:10.2174/1871527320666210526154801.PMID34042038.S2CID235217854.
^Harrington, Kevin; Freeman, Daniel J.; Kelly, Beth; Harper, James; Soria, Jean-Charles (September 2019). "Optimizing oncolytic virotherapy in cancer treatment".Nature Reviews Drug Discovery.18 (9):689–706.doi:10.1038/s41573-019-0029-0.ISSN1474-1784.PMID31292532.S2CID256745869.
^Jabbari M, Pourmoradian S, Eini-Zinab H, Mosharkesh E, Hosseini Balam F, Yaghmaei Y, Yadegari A, Amini B, Arman Moghadam D, Barati M, Hekmatdoost A (2022). "Levels of evidence for the association between different food groups/items consumption and the risk of various cancer sites: an umbrella review".Int J Food Sci Nutr.73 (7):861–874.doi:10.1080/09637486.2022.2103523.PMID35920747.S2CID251280745.
^Vieira AR, Abar L, Chan DSM, Vingeliene S, Polemiti E, Stevens C, Greenwood D, Norat T. (2017). "Foods and beverages and colorectal cancer risk: a systematic review and meta-analysis of cohort studies, an update of the evidence of the WCRF-AICR Continuous Update Project".Annals of Oncology.28 (8):1788–1802.doi:10.1093/annonc/mdx171.hdl:10044/1/48313.PMID28407090.{{cite journal}}: CS1 maint: multiple names: authors list (link)
^Magani, Sri Krishna Jayadev; Mupparthi, Sri Durgambica; Gollapalli, Bhanu Prakash; Shukla, Dhananjay; Tiwari, A. K.; Gorantala, Jyotsna; Yarla, Nagendra Sastry; Tantravahi, Srinivasan (2020). "Salidroside — Can it be a Multifunctional Drug?".Current Drug Metabolism.21 (7):512–524.doi:10.2174/1389200221666200610172105.PMID32520682.S2CID219588131.
.jpg)
