Cancer research

Source: Wikipedia, the free encyclopedia.

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

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.

Cancer research is done in academia, research institutes, and corporate environments, and is largely government funded.[citation needed]

History

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]

Seminal papers

Some of the most highly cited and most influential research reports include:

Types of research

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

Epidemiologic analysis indicates that at least 35% of all cancer deaths in the world could now be avoided by primary prevention.[3] According to a newer GBD systematic analysis, in 2019, ~44% of all cancer deaths – or ~4.5 M deaths or ~105 million lost disability-adjusted life years – were due to known clearly preventable risk factors, led by smoking, alcohol use and high BMI.[4]

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 to 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]

Detection

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, to develop novel ways of cancer screening and to increase detection rates.[citation needed][further explanation needed]

For example:

Treatment

Emerging topics of cancer treatment research include:

Cause and development of cancer

Numerous cell 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. 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

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)."[32] 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.[33]

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.[34]

Cancer epigenetics

Cancer epigenetics is the study of epigenetic modifications to the DNA of cancer 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, than genetic mutations in a cell's transformation to cancer. The disturbance of epigenetic processes in cancers, can lead to a loss of expression of genes that occurs about 10 times more frequently by transcription silencing (caused by epigenetic promoter hypermethylation of CpG 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 66 hitchhiker 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 of tumor suppressor genes and activation of oncogenes by altered CpG island methylation patterns, histone modifications, and dysregulation of DNA binding proteins. There are several medications which have epigenetic impact, that are now used in a number of these diseases.

Cancer growth

AMPK is thought to be a major element or mechanism in cancer-related effects of diet. It modulates the activity of cellular survival signaling such as mTOR and Akt, leading to cell growth inhibition which is relevant to cancer growth. Targeting AMPK has become a novel strategy for cancer prevention and treatment.[42][43][44] Potential complementary or preventive options under investigation include periods of caloric restriction and AMPK agonists (typically mTOR inhibitors).[45][46][47][48][49][50] However, AMPK can also promote cancer in some[clarification needed] settings.[42][47]

Diet and cancer

This advertisement suggests a healthy diet helps to prevent cancer.

Dietary factors are recognized as having a significant effect on the risk of cancers, with different dietary elements both increasing and reducing risk. Diet and obesity may be related to up to 30–35% of cancer deaths,[51] while physical inactivity appears to be related to 7% risk of cancer occurrence.[52]

While many dietary recommendations have been proposed to reduce the risk of cancer, few have significant supporting scientific evidence.[53][54][55] Obesity and drinking alcohol have been correlated with the incidence and progression of some cancers.[53] Lowering the consumption of sweetened beverages is recommended as a measure to address obesity.[56]

Some specific foods are linked to specific cancers. There is strong evidence that processed meat and red meat intake increases risk of colorectal cancer.[57][58][59][60] Aflatoxin B1, a frequent food contaminant, increases risk of liver cancer,[61] while drinking coffee is associated with a reduced risk.[62] Betel nut chewing causes oral cancer.[61] Stomach cancer is more common in Japan due to its high-salt diet.[61][63] Immigrant communities tend to develop the risk of their new country, often within one generation, suggesting a substantial link between diet and cancer.[64]

Dietary recommendations for cancer prevention typically include weight management and eating a healthy diet, consisting mainly of "vegetables, fruit, whole grains and fish, and a reduced intake of red meat, animal fat, and refined sugar."[53] A healthy dietary pattern may lower cancer risk by 10-20%.[65]

Periods of intermittent fasting (time-restricted feeding which may not include caloric restriction) is investigated for potential usefulness in cancer prevention and treatment and as of 2021 additional trials are needed to elucidate the risks and benefits.[66][67][68][69] In some cases, "caloric restrictions could hinder both cancer growth and progression, besides enhancing the efficacy of chemotherapy and radiation therapy".[70] Caloric restriction mimetics, including some present in foods like spermidine, are also investigated for these or similar reasons.[71][72] Such and similar dietary supplements may contribute to prevention or treatment, with candidate substances including apigenin,[73][74][75] berberine,[76][77][78][79][80] jiaogulan,[81] and rhodiola rosea.[82][83]

Research funding

Cancer research is funded by government grants, charitable foundations and pharmaceutical and biotechnology companies.[84]

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.[85] 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.[85] 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.[85] Half of Europe's non-commercial cancer research is funded by charitable organizations.[85]

The National Cancer Institute is the major funding institution in the United States. In the 2016 fiscal year, the NCI funded $5.2 billion in cancer research.[86]

Difficulties

Difficulties inherent to cancer research are shared with many types of biomedical 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 be replicated.[87][88][89][90]

Replicability

Graphic of results and barriers. 193 experiments were designed, 87 were initiated, and 50 were completed.
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 at Amgen, 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.[91] 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.[92][93] A survey of cancer researchers found that half of them had been unable to reproduce a published result.[94] 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).[95]

Public participation

Distributed computing

One can share computer time for distributed cancer research projects like Help Conquer Cancer.[96] 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. Vodafone has also partnered with the Garvan Institute to create the DreamLab Project, which uses distributed computing via an app on cellphones to perform cancer research.

Clinical trials

MatchMiner overview of data flow and modes of use[97]

Members of the public can also join clinical 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. One open source platform matches genomically profiled cancer patients to precision medicine drug trials.[98][97]

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

Organizations

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

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.[99] 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

References

  1. ^ "Early Theories about Cancer Causes – American Cancer Society". www.cancer.org. Archived from the original on 9 May 2018. Retrieved 9 May 2018.
  2. ^ "Milestone (1971): President Nixon declares war on cancer". dtp.cancer.gov. Archived from the original on 3 December 2017. Retrieved 9 May 2018.
  3. ^ a b c Song M, Vogelstein B, Giovannucci EL, Willett WC, Tomasetti C. Cancer prevention: Molecular and epidemiologic consensus. Science. 2018 Sep 28;361(6409):1317–1318. doi: 10.1126/science.aau3830. PMID 30262488; PMCID: PMC6260589
  4. ^ Tran, Khanh Bao; Lang, Justin J.; Compton, Kelly; Xu, Rixing; Acheson, Alistair R.; Henrikson, Hannah Jacqueline; Kocarnik, Jonathan M.; Penberthy, Louise; Aali, Amirali; Abbas, Qamar; et al. (20 August 2022). "The global burden of cancer attributable to risk factors, 2010–19: a systematic analysis for the Global Burden of Disease Study 2019". The Lancet. 400 (10352): 563–591. doi:10.1016/S0140-6736(22)01438-6. ISSN 0140-6736. PMC 9395583. PMID 35988567.
  5. ^ Wu S, Powers S, Zhu W, Hannun YA (January 2016). "Substantial contribution of extrinsic risk factors to cancer development". Nature. 529 (7584): 43–7. Bibcode:2016Natur.529...43W. doi:10.1038/nature16166. PMC 4836858. PMID 26675728.
  6. ^ Degasperi, Andrea; Zou, Xueqing; Dias Amarante, Tauanne; Martinez-Martinez, Andrea; et al. (22 April 2022). "Substitution mutational signatures in whole-genome–sequenced cancers in the UK population". Science. 376 (6591): abl9283. doi:10.1126/science.abl9283. ISSN 0036-8075. PMC 7613262. PMID 35949260. S2CID 248334490.
  7. ^ Quach, Katyanna. "Harvard boffins build multimodal AI system to predict cancer". The Register. Retrieved 16 September 2022.
  8. ^ Chen, Richard J.; Lu, Ming Y.; Williamson, Drew F. K.; Chen, Tiffany Y.; Lipkova, Jana; Noor, Zahra; Shaban, Muhammad; Shady, Maha; Williams, Mane; Joo, Bumjin; Mahmood, Faisal (8 August 2022). "Pan-cancer integrative histology-genomic analysis via multimodal deep learning". Cancer Cell. 40 (8): 865–878.e6. doi:10.1016/j.ccell.2022.07.004. ISSN 1535-6108. PMC 10397370. PMID 35944502. S2CID 251456162.
  9. ^ Zimmer, Carl (29 September 2022). "A New Approach to Spotting Tumors: Look for Their Microbes". The New York Times. Retrieved 19 October 2022.
  10. ^ Dohlman, Anders B.; Klug, Jared; Mesko, Marissa; Gao, Iris H.; Lipkin, Steven M.; Shen, Xiling; Iliev, Iliyan D. (29 September 2022). "A pan-cancer mycobiome analysis reveals fungal involvement in gastrointestinal and lung tumors". Cell. 185 (20): 3807–3822.e12. doi:10.1016/j.cell.2022.09.015. ISSN 0092-8674. PMC 9564002. PMID 36179671.
  11. ^ Narunsky-Haziza, Lian; Sepich-Poore, Gregory D.; Livyatan, Ilana; Asraf, Omer; Martino, Cameron; Nejman, Deborah; Gavert, Nancy; Stajich, Jason E.; Amit, Guy; González, Antonio; Wandro, Stephen; Perry, Gili; Ariel, Ruthie; Meltser, Arnon; Shaffer, Justin P.; Zhu, Qiyun; Balint-Lahat, Nora; Barshack, Iris; Dadiani, Maya; Gal-Yam, Einav N.; Patel, Sandip Pravin; Bashan, Amir; Swafford, Austin D.; Pilpel, Yitzhak; Knight, Rob; Straussman, Ravid (29 September 2022). "Pan-cancer analyses reveal cancer-type-specific fungal ecologies and bacteriome interactions". Cell. 185 (20): 3789–3806.e17. doi:10.1016/j.cell.2022.09.005. ISSN 0092-8674. PMC 9567272. PMID 36179670.
  12. ^ Piqueret, Baptiste; Montaudon, Élodie; Devienne, Paul; Leroy, Chloé; Marangoni, Elisabetta; Sandoz, Jean-Christophe; d'Ettorre, Patrizia (25 January 2023). "Ants act as olfactory bio-detectors of tumours in patient-derived xenograft mice". Proceedings of the Royal Society B: Biological Sciences. 290 (1991): 20221962. doi:10.1098/rspb.2022.1962. ISSN 0962-8452. PMC 9874262. PMID 36695032.
  13. ^ 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. PMID 18990084. S2CID 83589014.
  14. ^ Chen, Kok-Siong; Reinshagen, Clemens; Van Schaik, Thijs A.; Rossignoli, Filippo; Borges, Paulo; Mendonca, Natalia Claire; Abdi, Reza; Simon, Brennan; Reardon, David A.; Wakimoto, Hiroaki; Shah, Khalid (4 January 2023). "Bifunctional cancer cell–based vaccine concomitantly drives direct tumor killing and antitumor immunity". Science Translational Medicine. 15 (677): eabo4778. doi:10.1126/scitranslmed.abo4778. ISSN 1946-6234. PMC 10068810. PMID 36599004. S2CID 255416438.
  15. ^ "Gene Therapy, Cancer-Killing Viruses And New Drugs Highlight Novel Approaches To Cancer Treatment". Medical News Today. Retrieved 24 April 2007.
  16. ^ "World first gene therapy trial for leukaemia". LLR. Archived from the original on 2 August 2013. Retrieved 23 July 2013.
  17. ^ Chinese scientists to pioneer first human CRISPR trial
  18. ^ Schmidt, Christine K.; Medina-Sánchez, Mariana; Edmondson, Richard J.; Schmidt, Oliver G. (5 November 2020). "Engineering microrobots for targeted cancer therapies from a medical perspective". Nature Communications. 11 (1): 5618. Bibcode:2020NatCo..11.5618S. doi:10.1038/s41467-020-19322-7. ISSN 2041-1723. PMC 7645678. PMID 33154372.
  19. ^ Gwisai, T.; Mirkhani, N.; Christiansen, M. G.; Nguyen, T. T.; Ling, V.; Schuerle, S. (26 October 2022). "Magnetic torque–driven living microrobots for increased tumor infiltration". Science Robotics. 7 (71): eabo0665. bioRxiv 10.1101/2022.01.03.473989. doi:10.1126/scirobotics.abo0665. ISSN 2470-9476. PMID 36288270. S2CID 253160428.
  20. ^ 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): 531–539. doi:10.2174/1871527320666210526154801. PMID 34042038. S2CID 235217854.
  21. ^ Contreras-Llano, Luis E.; Liu, Yu-Han; Henson, Tanner; Meyer, Conary C.; Baghdasaryan, Ofelya; Khan, Shahid; Lin, Chi-Long; Wang, Aijun; Hu, Che-Ming J.; Tan, Cheemeng (11 January 2023). "Engineering Cyborg Bacteria Through Intracellular Hydrogelation". Advanced Science. 10 (9): 2204175. doi:10.1002/advs.202204175. ISSN 2198-3844. PMC 10037956. PMID 36628538.
  22. ^ Lawler, Sean E.; Speranza, Maria-Carmela; Cho, Choi-Fong; Chiocca, E. Antonio (1 June 2017). "Oncolytic Viruses in Cancer Treatment: A Review". JAMA Oncology. 3 (6): 841–849. doi:10.1001/jamaoncol.2016.2064. PMID 27441411. S2CID 39321536.
  23. ^ 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. ISSN 1474-1784. PMID 31292532. S2CID 256745869.
  24. ^ Osborne, Margaret. "Small Cancer Trial Resulted in Complete Remission for All Participants". Smithsonian Magazine. Retrieved 21 July 2022.
  25. ^ Cercek, Andrea; Lumish, Melissa; Sinopoli, Jenna; Weiss, Jill; Shia, Jinru; Lamendola-Essel, Michelle; El Dika, Imane H.; Segal, Neil; Shcherba, Marina; Sugarman, Ryan; Stadler, Zsofia; Yaeger, Rona; Smith, J. Joshua; Rousseau, Benoit; Argiles, Guillem; Patel, Miteshkumar; Desai, Avni; Saltz, Leonard B.; Widmar, Maria; Iyer, Krishna; Zhang, Janie; Gianino, Nicole; Crane, Christopher; Romesser, Paul B.; Pappou, Emmanouil P.; Paty, Philip; Garcia-Aguilar, Julio; Gonen, Mithat; Gollub, Marc; Weiser, Martin R.; Schalper, Kurt A.; Diaz, Luis A. (23 June 2022). "PD-1 Blockade in Mismatch Repair–Deficient, Locally Advanced Rectal Cancer". New England Journal of Medicine. 386 (25): 2363–2376. doi:10.1056/NEJMoa2201445. ISSN 0028-4793. PMC 9492301. PMID 35660797. S2CID 249395846.
  26. ^ "Trastuzumab Deruxtecan Leads to Longer PFS and OS Compared with Chemotherapy in Previously Treated HER2-Low Unresectable or Metastatic Breast Cancer". www.esmo.org. Retrieved 21 July 2022.
  27. ^ Modi, Shanu; Jacot, William; Yamashita, Toshinari; Sohn, Joohyuk; Vidal, Maria; Tokunaga, Eriko; Tsurutani, Junji; Ueno, Naoto T.; Prat, Aleix; Chae, Yee Soo; Lee, Keun Seok; Niikura, Naoki; Park, Yeon Hee; Xu, Binghe; Wang, Xiaojia; Gil-Gil, Miguel; Li, Wei; Pierga, Jean-Yves; Im, Seock-Ah; Moore, Halle C. F.; Rugo, Hope S.; Yerushalmi, Rinat; Zagouri, Flora; Gombos, Andrea; Kim, Sung-Bae; Liu, Qiang; Luo, Ting; Saura, Cristina; Schmid, Peter; Sun, Tao; Gambhire, Dhiraj; Yung, Lotus; Wang, Yibin; Singh, Jasmeet; Vitazka, Patrik; Meinhardt, Gerold; Harbeck, Nadia; Cameron, David A. (5 June 2022). "Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer". New England Journal of Medicine. 387 (1): 9–20. doi:10.1056/NEJMoa2203690. hdl:2445/197309. PMC 10561652. PMID 35665782. S2CID 249418284.
  28. ^ "Scientists harness light therapy to target and kill cancer cells in world first". The Guardian. 17 June 2022. Retrieved 21 June 2022.
  29. ^ Mączyńska, Justyna; Raes, Florian; Da Pieve, Chiara; Turnock, Stephen; Boult, Jessica K. R.; Hoebart, Julia; Niedbala, Marcin; Robinson, Simon P.; Harrington, Kevin J.; Kaspera, Wojciech; Kramer-Marek, Gabriela (21 January 2022). "Triggering anti-GBM immune response with EGFR-mediated photoimmunotherapy". BMC Medicine. 20 (1): 16. doi:10.1186/s12916-021-02213-z. ISSN 1741-7015. PMC 8780306. PMID 35057796.
  30. ^ a b Cerwenka A, Lanier LL (February 2016). "Natural killer cell memory in infection, inflammation and cancer". Nature Reviews. Immunology. 16 (2): 112–123. doi:10.1038/nri.2015.9. PMID 26806484. S2CID 361806.
  31. ^ Zhu, Shaoming; Zhang, Tian; Zheng, Lei; Liu, Hongtao; Song, Wenru; Liu, Delong; Li, Zihai; Pan, Chong-xian (December 2021). "Combination strategies to maximize the benefits of cancer immunotherapy". Journal of Hematology & Oncology. 14 (1): 156. doi:10.1186/s13045-021-01164-5. PMC 8475356. PMID 34579759.
  32. ^ Futreal PA, Coin L, Marshall M, Down T, Hubbard T, Wooster R, et al. (March 2004). "A census of human cancer genes". Nature Reviews. Cancer. 4 (3): 177–183. doi:10.1038/nrc1299. PMC 2665285. PMID 14993899.
  33. ^ Forbes S, Clements J, Dawson E, Bamford S, Webb T, Dogan A, et al. (January 2006). "COSMIC 2005". British Journal of Cancer. 94 (2): 318–322. doi:10.1038/sj.bjc.6602928. PMC 2361125. PMID 16421597.
  34. ^ 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.
  35. ^ Sharma S, Kelly TK, Jones PA (January 2010). "Epigenetics in cancer". Carcinogenesis. 31 (1): 27–36. doi:10.1093/carcin/bgp220. PMC 2802667. PMID 19752007.
  36. ^ Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Kinzler KW (March 2013). "Cancer genome landscapes". Science. 339 (6127): 1546–1558. Bibcode:2013Sci...339.1546V. doi:10.1126/science.1235122. PMC 3749880. PMID 23539594.
  37. ^ Illingworth RS, Gruenewald-Schneider U, Webb S, Kerr AR, James KD, Turner DJ, et al. (September 2010). "Orphan CpG islands identify numerous conserved promoters in the mammalian genome". PLOS Genetics. 6 (9): e1001134. doi:10.1371/journal.pgen.1001134. PMC 2944787. PMID 20885785.
  38. ^ Wei J, Li G, Dang S, Zhou Y, Zeng K, Liu M (2016). "Discovery and Validation of Hypermethylated Markers for Colorectal Cancer". Disease Markers. 2016: 2192853. doi:10.1155/2016/2192853. PMC 4963574. PMID 27493446.
  39. ^ Beggs AD, Jones A, El-Bahrawy M, El-Bahwary M, Abulafi M, Hodgson SV, Tomlinson IP (April 2013). "Whole-genome methylation analysis of benign and malignant colorectal tumours". The Journal of Pathology. 229 (5): 697–704. doi:10.1002/path.4132. PMC 3619233. PMID 23096130.
  40. ^ Novak K (December 2004). "Epigenetics changes in cancer cells". MedGenMed. 6 (4): 17. PMC 1480584. PMID 15775844.
  41. ^ Banno K, Kisu I, Yanokura M, Tsuji K, Masuda K, Ueki A, et al. (September 2012). "Epimutation and cancer: a new carcinogenic mechanism of Lynch syndrome (Review)". International Journal of Oncology. 41 (3): 793–797. doi:10.3892/ijo.2012.1528. PMC 3582986. PMID 22735547.
  42. ^ a b Wang, Zhiyu; Wang, Neng; Liu, Pengxi; Xie, Xiaoming (2016). "AMPK and Cancer". AMP-activated Protein Kinase. Experientia Supplementum. Vol. 107. Springer International Publishing. pp. 203–226. doi:10.1007/978-3-319-43589-3_9. ISBN 978-3-319-43587-9. PMID 27812982. {{cite book}}: |journal= ignored (help)
  43. ^ Carling, David (April 2017). "AMPK signalling in health and disease". Current Opinion in Cell Biology. 45: 31–37. doi:10.1016/j.ceb.2017.01.005. hdl:10044/1/45767. PMID 28232179.
  44. ^ Li, Jin; Zhong, Liping; Wang, Fengzhong; Zhu, Haibo (May 2017). "Dissecting the role of AMP-activated protein kinase in human diseases". Acta Pharmaceutica Sinica B. 7 (3): 249–259. doi:10.1016/j.apsb.2016.12.003. PMC 5430814. PMID 28540163.
  45. ^ Yung, Mingo M.H.; Ngan, Hextan Y.S.; Chan, David W. (1 April 2016). "Targeting AMPK signaling in combating ovarian cancers: opportunities and challenges". Acta Biochimica et Biophysica Sinica. 48 (4): 301–317. doi:10.1093/abbs/gmv128. PMC 4886241. PMID 26764240.
  46. ^ Meynet, Ophélie; Ricci, Jean-Ehrland (August 2014). "Caloric restriction and cancer: molecular mechanisms and clinical implications". Trends in Molecular Medicine. 20 (8): 419–427. doi:10.1016/j.molmed.2014.05.001. ISSN 1471-499X. PMID 24916302.
  47. ^ a b Fay, Judith R.; Steele, Vernon; Crowell, James A. (1 April 2009). "Energy Homeostasis and Cancer Prevention: The AMP-Activated Protein Kinase". Cancer Prevention Research. 2 (4): 301–309. doi:10.1158/1940-6207.CAPR-08-0166. PMID 19336731. S2CID 22495750.
  48. ^ Skuli, Sarah J.; Alomari, Safwan; Gaitsch, Hallie; Bakayoko, A'ishah; Skuli, Nicolas; Tyler, Betty M. (19 May 2022). "Metformin and Cancer, an Ambiguanidous Relationship". Pharmaceuticals. 15 (5): 626. doi:10.3390/ph15050626. PMC 9144507. PMID 35631452.
  49. ^ Ingram, Donald K.; Roth, George S. (June 2021). "Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics". GeroScience. 43 (3): 1159–1169. doi:10.1007/s11357-020-00298-7. PMC 8190254. PMID 33184758.
  50. ^ Guigas, Bruno; Viollet, Benoit (2016). "Targeting AMPK: From Ancient Drugs to New Small-Molecule Activators". AMP-activated Protein Kinase. Experientia Supplementum. Vol. 107. pp. 327–350. doi:10.1007/978-3-319-43589-3_13. ISBN 978-3-319-43587-9. PMID 27812986. {{cite book}}: |journal= ignored (help)
  51. ^ Anand P, Kunnumakkara AB, Kunnumakara AB, Sundaram C, Harikumar KB, Tharakan ST, et al. (September 2008). "Cancer is a preventable disease that requires major lifestyle changes". Pharmaceutical Research. 25 (9): 2097–2116. doi:10.1007/s11095-008-9661-9. PMC 2515569. PMID 18626751.
  52. ^ Moore SC, Lee IM, Weiderpass E, Campbell PT, Sampson JN, Kitahara CM, et al. (June 2016). "Association of Leisure-Time Physical Activity With Risk of 26 Types of Cancer in 1.44 Million Adults". JAMA Internal Medicine. 176 (6): 816–825. doi:10.1001/jamainternmed.2016.1548. PMC 5812009. PMID 27183032.
  53. ^ a b c Wicki A, Hagmann J (9 September 2011). "Diet and cancer". Swiss Medical Weekly. 141: w13250. doi:10.4414/smw.2011.13250. PMID 21904992.
  54. ^ Papadimitriou N, Markozannes G, Kanellopoulou A, Critselis E, Alhardan S, Karafousia V, Kasimis JC, Katsaraki C, Papadopoulou A, Zografou M, Lopez DS, Chan DS, Kyrgiou M, Ntzani E, Cross AJ, Marrone MT, Platz EA, Gunter MJ, Tsilidis KK (2021). "An umbrella review of the evidence associating diet and cancer risk at 11 anatomical sites". Nature Communications. 12 (1): 4579. Bibcode:2021NatCo..12.4579P. doi:10.1038/s41467-021-24861-8. PMC 8319326. PMID 34321471.
  55. ^ 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. PMID 35920747. S2CID 251280745.
  56. ^ Stewart BW, Wild CP, eds. (2014). "Ch. 2: Cancer Etiology § 6 Diet, obesity and physical activity". World Cancer Report 2014. World Health Organization. pp. 124–33. ISBN 978-92-832-0429-9.
  57. ^ 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. PMID 28407090.{{cite journal}}: CS1 maint: multiple names: authors list (link)
  58. ^ "Meat, fish, dairy and cancer risk". wcrf.org. Retrieved 24 April 2023.
  59. ^ "Red Meat and Processed Meat Consumption". progressreport.cancer.gov. Retrieved 24 April 2023.
  60. ^ "Red Meat (Beef, Pork, Lamb): Increases Risk of Colorectal Cancer". aicr.org. Retrieved 24 April 2023.
  61. ^ a b c Park S, Bae J, Nam BH, Yoo KY (2008). "Aetiology of cancer in Asia" (PDF). Asian Pacific Journal of Cancer Prevention. 9 (3): 371–380. PMID 18990005.
  62. ^ Yu C, Cao Q, Chen P, Yang S, Deng M, Wang Y, Li L (December 2016). "An updated dose-response meta-analysis of coffee consumption and liver cancer risk". Scientific Reports. 6 (1): 37488. Bibcode:2016NatSR...637488Y. doi:10.1038/srep37488. PMC 5133591. PMID 27910873.
  63. ^ Brenner H, Rothenbacher D, Arndt V (2009). "Epidemiology of Stomach Cancer". In Mukesh V (ed.). Cancer Epidemiology. Methods in Molecular Biology. Vol. 472. pp. 467–477. doi:10.1007/978-1-60327-492-0_23. ISBN 978-1-60327-491-3. PMC 2166976. PMID 19107449.
  64. ^ Buell P, Dunn JE (May 1965). "Cancer mortality among Japanese Issei and Nisei of California". Cancer. 18 (5): 656–664. doi:10.1002/1097-0142(196505)18:5<656::AID-CNCR2820180515>3.0.CO;2-3. PMID 14278899.
  65. ^ "Preventing Cancer". hsph.harvard.edu. Retrieved 24 April 2023.
  66. ^ Clifton, Katherine K.; Ma, Cynthia X.; Fontana, Luigi; Peterson, Lindsay L. (November 2021). "Intermittent fasting in the prevention and treatment of cancer". CA: A Cancer Journal for Clinicians. 71 (6): 527–546. doi:10.3322/caac.21694. ISSN 0007-9235. PMID 34383300. S2CID 236989849.
  67. ^ Manoogian, Emily N. C.; Panda, Satchidananda (1 October 2017). "Circadian rhythms, time-restricted feeding, and healthy aging". Ageing Research Reviews. 39: 59–67. doi:10.1016/j.arr.2016.12.006. ISSN 1568-1637. PMC 5814245. PMID 28017879.
  68. ^ Brandhorst, Sebastian; Longo, Valter D. (2016). "Fasting and Caloric Restriction in Cancer Prevention and Treatment". Metabolism in Cancer. Recent Results in Cancer Research. Vol. 207. Springer International Publishing. pp. 241–266. doi:10.1007/978-3-319-42118-6_12. ISBN 978-3-319-42116-2. PMC 7476366. PMID 27557543. S2CID 42198775. {{cite book}}: |journal= ignored (help)
  69. ^ Alidadi, Mona; Banach, Maciej; Guest, Paul C.; Bo, Simona; Jamialahmadi, Tannaz; Sahebkar, Amirhossein (1 August 2021). "The effect of caloric restriction and fasting on cancer". Seminars in Cancer Biology. 73: 30–44. doi:10.1016/j.semcancer.2020.09.010. ISSN 1044-579X. PMID 32977005. S2CID 221938415.
  70. ^ Ibrahim, Ezzeldin M.; Al-Foheidi, Meteb H.; Al-Mansour, Mubarak M. (1 May 2021). "Energy and caloric restriction, and fasting and cancer: a narrative review". Supportive Care in Cancer. 29 (5): 2299–2304. doi:10.1007/s00520-020-05879-y. ISSN 1433-7339. PMC 7981322. PMID 33190181. S2CID 226945778.
  71. ^ Hofer, Sebastian J.; Davinelli, Sergio; Bergmann, Martina; Scapagnini, Giovanni; Madeo, Frank (2021). "Caloric Restriction Mimetics in Nutrition and Clinical Trials". Frontiers in Nutrition. 8: 717343. doi:10.3389/fnut.2021.717343. ISSN 2296-861X. PMC 8450594. PMID 34552954.
  72. ^ Madeo, Frank; Eisenberg, Tobias; Pietrocola, Federico; Kroemer, Guido (26 January 2018). "Spermidine in health and disease". Science. 359 (6374): eaan2788. doi:10.1126/science.aan2788. ISSN 0036-8075. PMID 29371440. S2CID 206659415.
  73. ^ Imran, Muhammad; Aslam Gondal, Tanweer; Atif, Muhammad; Shahbaz, Muhammad; Batool Qaisarani, Tahira; Hanif Mughal, Muhammad; Salehi, Bahare; Martorell, Miquel; Sharifi-Rad, Javad (August 2020). "Apigenin as an anticancer agent". Phytotherapy Research. 34 (8): 1812–1828. doi:10.1002/ptr.6647. ISSN 0951-418X. PMID 32059077. S2CID 211122428.
  74. ^ Shukla, Sanjeev; Gupta, Sanjay (1 June 2010). "Apigenin: A Promising Molecule for Cancer Prevention". Pharmaceutical Research. 27 (6): 962–978. doi:10.1007/s11095-010-0089-7. ISSN 1573-904X. PMC 2874462. PMID 20306120.
  75. ^ Shankar, Eswar; Goel, Aditi; Gupta, Karishma; Gupta, Sanjay (1 December 2017). "Plant Flavone Apigenin: an Emerging Anticancer Agent". Current Pharmacology Reports. 3 (6): 423–446. doi:10.1007/s40495-017-0113-2. ISSN 2198-641X. PMC 5791748. PMID 29399439.
  76. ^ Samadi, Parisa; Sarvarian, Parisa; Gholipour, Elham; Asenjan, Karim Shams; Aghebati-Maleki, Leili; Motavalli, Roza; Hojjat-Farsangi, Mohammad; Yousefi, Mehdi (October 2020). "Berberine: A novel therapeutic strategy for cancer". IUBMB Life. 72 (10): 2065–2079. doi:10.1002/iub.2350. ISSN 1521-6543. PMID 32735398. S2CID 220893166.
  77. ^ Zhong, Xiao-Dan; Chen, Li-Juan; Xu, Xin-Yang; Liu, Yan-Jun; Tao, Fan; Zhu, Ming-Hui; Li, Chang-Yun; Zhao, Dan; Yang, Guan-Jun; Chen, Jiong (2022). "Berberine as a potential agent for breast cancer therapy". Frontiers in Oncology. 12: 993775. doi:10.3389/fonc.2022.993775. ISSN 2234-943X. PMC 9480097. PMID 36119505.
  78. ^ Wang, Ye; Liu, Yanfang; Du, Xinyang; Ma, Hong; Yao, Jing (30 January 2020). "The Anti-Cancer Mechanisms of Berberine: A Review". Cancer Management and Research. 12: 695–702. doi:10.2147/CMAR.S242329. PMC 6996556. PMID 32099466.
  79. ^ Vlavcheski, Filip; O’Neill, Eric J.; Gagacev, Filip; Tsiani, Evangelia (January 2022). "Effects of Berberine against Pancreatitis and Pancreatic Cancer". Molecules. 27 (23): 8630. doi:10.3390/molecules27238630. ISSN 1420-3049. PMC 9738201. PMID 36500723.
  80. ^ Guamán Ortiz, Luis Miguel; Lombardi, Paolo; Tillhon, Micol; Scovassi, Anna Ivana (August 2014). "Berberine, an Epiphany Against Cancer". Molecules. 19 (8): 12349–12367. doi:10.3390/molecules190812349. ISSN 1420-3049. PMC 6271598. PMID 25153862.
  81. ^ Su, Chao; Li, Nan; Ren, Ruru; Wang, Yingli; Su, Xiaojuan; Lu, Fangfang; Zong, Rong; Yang, Lingling; Ma, Xueqin (January 2021). "Progress in the Medicinal Value, Bioactive Compounds, and Pharmacological Activities of Gynostemma pentaphyllum". Molecules. 26 (20): 6249. doi:10.3390/molecules26206249. ISSN 1420-3049. PMC 8540791. PMID 34684830.
  82. ^ Pu, Wei-ling; Zhang, Meng-ying; Bai, Ru-yu; Sun, Li-kang; Li, Wen-hua; Yu, Ying-li; Zhang, Yue; Song, Lei; Wang, Zhao-xin; Peng, Yan-fei; Shi, Hong; Zhou, Kun; Li, Tian-xiang (1 January 2020). "Anti-inflammatory effects of Rhodiola rosea L.: A review". Biomedicine & Pharmacotherapy. 121: 109552. doi:10.1016/j.biopha.2019.109552. ISSN 0753-3322. PMID 31715370. S2CID 207938536.
  83. ^ 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. PMID 32520682. S2CID 219588131.
  84. ^ "Federally Funded Cancer Research". asco.org. 8 February 2016. Archived from the original on 23 April 2018. Retrieved 9 May 2018.
  85. ^ a b c d Eckhouse S, Sullivan R (July 2006). "A survey of public funding of cancer research in the European union". PLOS Medicine. 3 (7): e267. doi:10.1371/journal.pmed.0030267. PMC 1513045. PMID 16842021.
  86. ^ "Funding Trends". National Cancer Institute. Archived from the original on 29 September 2017.
  87. ^ Alberts B, Kirschner MW, Tilghman S, Varmus H (April 2014). "Rescuing US biomedical research from its systemic flaws". Proceedings of the National Academy of Sciences of the United States of America. 111 (16): 5773–7. Bibcode:2014PNAS..111.5773A. doi:10.1073/pnas.1404402111. PMC 4000813. PMID 24733905.
  88. ^ Kolata G (23 April 2009). "Advances Elusive in the Drive to Cure Cancer". The New York Times. Archived from the original on 14 January 2012. Retrieved 29 December 2009.
  89. ^ Kolata G (27 June 2009). "Grant System Leads Cancer Researchers to Play It Safe". The New York Times. Archived from the original on 8 June 2011. Retrieved 29 December 2009.
  90. ^ Leaf C (22 March 2004). "Why We're Losing The War on Cancer". Fortune Magazine (CNN Money). Archived from the original on 2 May 2014.
  91. ^ Begley CG, Ellis LM (March 2012). "Drug development: Raise standards for preclinical cancer research". Nature (Comment article). 483 (7391): 531–533. Bibcode:2012Natur.483..531B. doi:10.1038/483531a. PMID 22460880. S2CID 4326966. (Erratum: doi:10.1038/485041e)
  92. ^ Haelle T (7 December 2021). "Dozens of major cancer studies can't be replicated". Science News. Retrieved 19 January 2022.
  93. ^ "Reproducibility Project: Cancer Biology". www.cos.io. Center for Open Science. Retrieved 19 January 2022.
  94. ^ Mobley A, Linder SK, Braeuer R, Ellis LM, Zwelling L (2013). Arakawa H (ed.). "A survey on data reproducibility in cancer research provides insights into our limited ability to translate findings from the laboratory to the clinic". PLOS ONE. 8 (5): e63221. Bibcode:2013PLoSO...863221M. doi:10.1371/journal.pone.0063221. PMC 3655010. PMID 23691000.
  95. ^ Van Noorden, Richard (18 July 2023). "Medicine is plagued by untrustworthy clinical trials. How many studies are faked or flawed?". Nature. 619 (7970): 454–458. Bibcode:2023Natur.619..454V. doi:10.1038/d41586-023-02299-w. PMID 37464079.
  96. ^ "Help Conquer Cancer". 19 November 2007. Archived from the original on 16 November 2007. Retrieved 19 November 2007.
  97. ^ a b Klein, Harry; Mazor, Tali; Siegel, Ethan; Trukhanov, Pavel; Ovalle, Andrea; Vecchio Fitz, Catherine Del; Zwiesler, Zachary; Kumari, Priti; Van Der Veen, Bernd; Marriott, Eric; Hansel, Jason; Yu, Joyce; Albayrak, Adem; Barry, Susan; Keller, Rachel B.; MacConaill, Laura E.; Lindeman, Neal; Johnson, Bruce E.; Rollins, Barrett J.; Do, Khanh T.; Beardslee, Brian; Shapiro, Geoffrey; Hector-Barry, Suzanne; Methot, John; Sholl, Lynette; Lindsay, James; Hassett, Michael J.; Cerami, Ethan (6 October 2022). "MatchMiner: an open-source platform for cancer precision medicine". npj Precision Oncology. 6 (1): 69. doi:10.1038/s41698-022-00312-5. ISSN 2397-768X. PMC 9537311. PMID 36202909.
  98. ^ "Researchers report genomic profiling from more than 110,000 tumors". News-Medical.net. 19 July 2022. Retrieved 20 November 2022.
  99. ^ "Cancer Awareness Dates". cancer.net. 19 December 2013. Archived from the original on 9 December 2017. Retrieved 9 May 2018.

External links