Cancer biomarker

Organizations and publications vary in their definition of biomarker. In many areas of medicine, biomarkers are limited to proteins identifiable or measurable in the blood or urine. However, the term is often used to cover any molecular, biochemical, physiological, or anatomical property that can be quantified or measured.

The National Cancer Institute (NCI), in particular, defines biomarker as a: “A biological molecule found in blood, other body fluids, or tissues that is a sign of a normal or abnormal process, or of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. Also called molecular marker and signature molecule."{{cite web |title=biomarker |work=NCI Dictionary of Cancer Terms |publisher=National Cancer Institute |url=http://www.cancer.gov/dictionary/?CdrID=45618.|date=2011-02-02 }}

In cancer research and medicine, biomarkers are used in three primary ways:{{cite web|title=Biomarkers in Cancer: An Introductory Guide for Advocates|url=http://researchadvocacy.org/images/uploads/downloads/BiomarkerinCancer_WebDownloadVersion.pdf|publisher=Research Advocacy Network|access-date=26 April 2013|year=2010|archive-url=https://web.archive.org/web/20131029200236/http://researchadvocacy.org/images/uploads/downloads/BiomarkerinCancer_WebDownloadVersion.pdf|archive-date=2013-10-29|url-status=dead}}

1. To help diagnose conditions, as in the case of identifying early stage cancers (diagnostic)
2. To forecast how aggressive a condition is, as in the case of determining a patient's ability to fare in the absence of treatment (prognostic)
3. To predict how well a patient will respond to treatment (predictive)

Cancer biomarkers, particular those associated with genetic mutations or epigenetic alterations, often offer a quantitative way to determine when individuals are predisposed to particular types of cancers. Notable examples of potentially predictive cancer biomarkers include mutations on genes KRAS, p53, EGFR, erbB2 for colorectal, esophageal, liver, and pancreatic cancer; mutations of genes BRCA1 and BRCA2 for breast and ovarian cancer; abnormal methylation of tumor suppressor genes p16, CDKN2B, and p14ARF for brain cancer; hypermethylation of MYOD1, CDH1, and CDH13 for cervical cancer; and hypermethylation of p16, p14, and RB1, for oral cancer.{{cite journal | vauthors = Verma M, Manne U | title = Genetic and epigenetic biomarkers in cancer diagnosis and identifying high risk populations | journal = Critical Reviews in Oncology/Hematology | volume = 60 | issue = 1 | pages = 9–18 | date = October 2006 | pmid = 16829121 | doi = 10.1016/j.critrevonc.2006.04.002 | url = https://zenodo.org/record/1258881 }}

Cancer biomarkers can also be useful in establishing a specific diagnosis. This is particularly the case when there is a need to determine whether tumors are of primary or metastatic origin. To make this distinction, researchers can screen the chromosomal alterations found on cells located in the primary tumor site against those found in the secondary site. If the alterations match, the secondary tumor can be identified as metastatic; whereas if the alterations differ, the secondary tumor can be identified as a distinct primary tumor.{{cite journal | vauthors = Leong PP, Rezai B, Koch WM, Reed A, Eisele D, Lee DJ, Sidransky D, Jen J, Westra WH | display-authors = 6 | title = Distinguishing second primary tumors from lung metastases in patients with head and neck squamous cell carcinoma | journal = Journal of the National Cancer Institute | volume = 90 | issue = 13 | pages = 972–977 | date = July 1998 | pmid = 9665144 | doi = 10.1093/jnci/90.13.972 | doi-access = free }} For example, people with tumors have high levels of circulating tumor DNA (ctDNA) due to tumor cells that have gone through apoptosis.{{cite journal | vauthors = Lapin M, Oltedal S, Tjensvoll K, Buhl T, Smaaland R, Garresori H, Javle M, Glenjen NI, Abelseth BK, Gilje B, Nordgård O | display-authors = 6 | title = Fragment size and level of cell-free DNA provide prognostic information in patients with advanced pancreatic cancer | journal = Journal of Translational Medicine | volume = 16 | issue = 1 | pages = 300 | date = November 2018 | pmid = 30400802 | pmc = 6218961 | doi = 10.1186/s12967-018-1677-2 | doi-access = free }} This tumor marker can be detected in the blood, saliva, or urine. The possibility of identifying an effective biomarker for early cancer diagnosis has recently been questioned, in light of the high molecular heterogeneity of tumors observed by next-generation sequencing studies.{{cite journal | vauthors = Dragani TA, Matarese V, Colombo F | title = Biomarkers for Early Cancer Diagnosis: Prospects for Success through the Lens of Tumor Genetics | journal = BioEssays | volume = 42 | issue = 4 | pages = e1900122 | date = April 2020 | pmid = 32128843 | doi = 10.1002/bies.201900122 | s2cid = 212406467 }}

Another use of biomarkers in cancer medicine is for disease prognosis, which take place after an individual has been diagnosed with cancer. Here biomarkers can be useful in determining the aggressiveness of an identified cancer as well as its likelihood of responding to a given treatment. In part, this is because tumors exhibiting particular biomarkers may be responsive to treatments tied to that biomarker's expression or presence. Examples of such prognostic biomarkers include elevated levels of metallopeptidase inhibitor 1 (TIMP1), a marker associated with more aggressive forms of multiple myeloma,{{cite journal | vauthors = Terpos E, Dimopoulos MA, Shrivastava V, Leitzel K, Christoulas D, Migkou M, Gavriatopoulou M, Anargyrou K, Hamer P, Kastritis E, Carney W, Lipton A | display-authors = 6 | title = High levels of serum TIMP-1 correlate with advanced disease and predict for poor survival in patients with multiple myeloma treated with novel agents | journal = Leukemia Research | volume = 34 | issue = 3 | pages = 399–402 | date = March 2010 | pmid = 19781774 | doi = 10.1016/j.leukres.2009.08.035 }} elevated estrogen receptor (ER) and/or progesterone receptor (PR) expression, markers associated with better overall survival in patients with breast cancer;{{cite journal | vauthors = Kuukasjärvi T, Kononen J, Helin H, Holli K, Isola J | title = Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy | journal = Journal of Clinical Oncology | volume = 14 | issue = 9 | pages = 2584–2589 | date = September 1996 | pmid = 8823339 | doi = 10.1200/jco.1996.14.9.2584 }}{{cite journal | vauthors = Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, Somerfield MR, Hayes DF, Bast RC | display-authors = 6 | title = American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer | journal = Journal of Clinical Oncology | volume = 25 | issue = 33 | pages = 5287–5312 | date = November 2007 | pmid = 17954709 | doi = 10.1200/JCO.2007.14.2364 }} HER2/neu gene amplification, a marker indicating a breast cancer will likely respond to trastuzumab treatment;{{cite journal | vauthors = Kröger N, Milde-Langosch K, Riethdorf S, Schmoor C, Schumacher M, Zander AR, Löning T | title = Prognostic and predictive effects of immunohistochemical factors in high-risk primary breast cancer patients | journal = Clinical Cancer Research | volume = 12 | issue = 1 | pages = 159–168 | date = January 2006 | pmid = 16397038 | doi = 10.1158/1078-0432.CCR-05-1340 | doi-access = free }}{{cite journal | vauthors = Vrbic S, Pejcic I, Filipovic S, Kocic B, Vrbic M | title = Current and future anti-HER2 therapy in breast cancer | journal = Journal of B.U.On. | volume = 18 | issue = 1 | pages = 4–16 | date = Jan–Mar 2013 | pmid = 23613383 }} a mutation in exon 11 of the proto-oncogene c-KIT, a marker indicating a gastrointestinal stromal tumor (GIST) will likely respond to imatinib treatment;{{cite journal | vauthors = Yoo C, Ryu MH, Ryoo BY, Beck MY, Kang YK | title = Efficacy, safety, and pharmacokinetics of imatinib dose escalation to 800 mg/day in patients with advanced gastrointestinal stromal tumors | journal = Investigational New Drugs | volume = 31 | issue = 5 | pages = 1367–1374 | date = October 2013 | pmid = 23591629 | doi = 10.1007/s10637-013-9961-8 | s2cid = 29477955 }}{{cite journal | vauthors = Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, McArthur G, Judson IR, Heinrich MC, Morgan JA, Desai J, Fletcher CD, George S, Bello CL, Huang X, Baum CM, Casali PG | display-authors = 6 | title = Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial | journal = Lancet | volume = 368 | issue = 9544 | pages = 1329–1338 | date = October 2006 | pmid = 17046465 | doi = 10.1016/S0140-6736(06)69446-4 | s2cid = 25931515 }} and mutations in the tyrosine kinase domain of EGFR1, a marker indicating a patient's non-small-cell lung carcinoma (NSCLC) will likely respond to gefitinib or erlotinib treatment.{{cite journal | vauthors = Herbst RS, Prager D, Hermann R, Fehrenbacher L, Johnson BE, Sandler A, Kris MG, Tran HT, Klein P, Li X, Ramies D, Johnson DH, Miller VA | display-authors = 6 | title = TRIBUTE: a phase III trial of erlotinib hydrochloride (OSI-774) combined with carboplatin and paclitaxel chemotherapy in advanced non-small-cell lung cancer | journal = Journal of Clinical Oncology | volume = 23 | issue = 25 | pages = 5892–5899 | date = September 2005 | pmid = 16043829 | doi = 10.1200/JCO.2005.02.840 | doi-access = free }}{{cite journal | vauthors = Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA | display-authors = 6 | title = Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib | journal = The New England Journal of Medicine | volume = 350 | issue = 21 | pages = 2129–2139 | date = May 2004 | pmid = 15118073 | doi = 10.1056/NEJMoa040938 | url = http://repository.cshl.edu/22429/1/EGFR%20Mutations.pdf }}

Cancer biomarkers can also be used to determine the most effective treatment regime for a particular person's cancer.{{cite journal | vauthors = Sawyers CL | title = The cancer biomarker problem | journal = Nature | volume = 452 | issue = 7187 | pages = 548–552 | date = April 2008 | pmid = 18385728 | doi = 10.1038/nature06913 | s2cid = 205213083 | bibcode = 2008Natur.452..548S }} Because of differences in each person's genetic makeup, some people metabolize or change the chemical structure of drugs differently. In some cases, decreased metabolism of certain drugs can create dangerous conditions in which high levels of the drug accumulate in the body. As such, drug dosing decisions in particular cancer treatments can benefit from screening for such biomarkers. An example is the gene encoding the enzyme thiopurine methyl-transferase (TPMPT).{{cite journal | vauthors = Karas-Kuzelicki N, Mlinaric-Rascan I | title = Individualization of thiopurine therapy: thiopurine S-methyltransferase and beyond | journal = Pharmacogenomics | volume = 10 | issue = 8 | pages = 1309–1322 | date = August 2009 | pmid = 19663675 | doi = 10.2217/pgs.09.78 }} Individuals with mutations in the TPMT gene are unable to metabolize large amounts of the leukemia drug, mercaptopurine, which potentially causes a fatal drop in white blood count for such patients. Patients with TPMT mutations are thus recommended to be given a lower dose of mercaptopurine for safety considerations.{{cite journal | vauthors = Relling MV, Hancock ML, Rivera GK, Sandlund JT, Ribeiro RC, Krynetski EY, Pui CH, Evans WE | display-authors = 6 | title = Mercaptopurine therapy intolerance and heterozygosity at the thiopurine S-methyltransferase gene locus | journal = Journal of the National Cancer Institute | volume = 91 | issue = 23 | pages = 2001–2008 | date = December 1999 | pmid = 10580024 | doi = 10.1093/jnci/91.23.2001 | doi-access = free }}

Cancer biomarkers have also shown utility in monitoring how well a treatment is working over time. Much research is going into this particular area, since successful biomarkers have the potential of providing significant cost reduction in patient care, as the current image-based tests such as CT and MRI for monitoring tumor status are highly costly.{{cite journal | vauthors = Schneider JE, Sidhu MK, Doucet C, Kiss N, Ohsfeldt RL, Chalfin D | title = Economics of cancer biomarkers | journal = Personalized Medicine | volume = 9 | issue = 8 | pages = 829–837 | date = November 2012 | pmid = 29776231 | doi = 10.2217/pme.12.87 }}

One notable biomarker garnering significant attention is the protein biomarker S100-beta in monitoring the response of malignant melanoma. In such melanomas, melanocytes, the cells that make pigment in our skin, produce the protein S100-beta in high concentrations dependent on the number of cancer cells. Response to treatment is thus associated with reduced levels of S100-beta in the blood of such individuals.{{cite journal | vauthors = Henze G, Dummer R, Joller-Jemelka HI, Böni R, Burg G | title = Serum S100--a marker for disease monitoring in metastatic melanoma | journal = Dermatology | volume = 194 | issue = 3 | pages = 208–212 | year = 1997 | pmid = 9187834 | doi = 10.1159/000246103 }}{{cite journal | vauthors = Harpio R, Einarsson R | title = S100 proteins as cancer biomarkers with focus on S100B in malignant melanoma | journal = Clinical Biochemistry | volume = 37 | issue = 7 | pages = 512–518 | date = July 2004 | pmid = 15234232 | doi = 10.1016/j.clinbiochem.2004.05.012 }}

Similarly, additional laboratory research has shown that tumor cells undergoing apoptosis can release cellular components such as cytochrome c, nucleosomes, cleaved cytokeratin-18, and E-cadherin. Studies have found that these macromolecules and others can be found in circulation during cancer therapy, providing a potential source of clinical metrics for monitoring treatment.

Cancer biomarkers can also offer value in predicting or monitoring cancer recurrence. The [http://www.oncotypedx.com/ Oncotype DX®] breast cancer assay is one such test used to predict the likelihood of breast cancer recurrence. This test is intended for women with early-stage (Stage I or II), node-negative, estrogen receptor-positive (ER+) invasive breast cancer who will be treated with hormone therapy. Oncotype DX looks at a panel of 21 genes in cells taken during tumor biopsy. The results of the test are given in the form of a recurrence score that indicates likelihood of recurrence at 10 years.{{cite journal | vauthors = Lamond NW, Skedgel C, Younis T | title = Is the 21-gene recurrence score a cost-effective assay in endocrine-sensitive node-negative breast cancer? | journal = Expert Review of Pharmacoeconomics & Outcomes Research | volume = 13 | issue = 2 | pages = 243–250 | date = April 2013 | pmid = 23570435 | doi = 10.1586/erp.13.4 | s2cid = 33661439 }}{{cite journal | vauthors = Biroschak JR, Schwartz GF, Palazzo JP, Toll AD, Brill KL, Jaslow RJ, Lee SY | title = Impact of Oncotype DX on treatment decisions in ER-positive, node-negative breast cancer with histologic correlation | journal = The Breast Journal | volume = 19 | issue = 3 | pages = 269–275 | date = May 2013 | pmid = 23614365 | doi = 10.1111/tbj.12099 | s2cid = 30895945 | doi-access = free }}

In addition to their use in cancer medicine, biomarkers are often used throughout the cancer drug discovery process. For instance, in the 1960s, researchers discovered the majority of patients with chronic myelogenous leukemia possessed a particular genetic abnormality on chromosomes 9 and 22 dubbed the Philadelphia chromosome. When these two chromosomes combine they create a cancer-causing gene known as BCR-ABL. In such patients, this gene acts as the principle initial point in all of the physiological manifestations of the leukemia. For many years, the BCR-ABL was simply used as a biomarker to stratify a certain subtype of leukemia. However, drug developers were eventually able to develop imatinib, a powerful drug that effectively inhibited this protein and significantly decreased production of cells containing the Philadelphia chromosome.{{cite journal | vauthors = Moen MD, McKeage K, Plosker GL, Siddiqui MA | title = Imatinib: a review of its use in chronic myeloid leukaemia | journal = Drugs | volume = 67 | issue = 2 | pages = 299–320 | year = 2007 | pmid = 17284091 | doi = 10.2165/00003495-200767020-00010 }}{{cite news| vauthors = Lemonick M, Park A |title=New Hope for Cancer |url= http://www.time.com/time/magazine/article/0,9171,999978,00.html |archive-url= https://web.archive.org/web/20071015042738/http://www.time.com/time/magazine/article/0,9171,999978,00.html |url-status=dead |archive-date=October 15, 2007 |access-date=26 April 2013 |newspaper=Time |date=May 28, 2001 }}

Another promising area of biomarker application is in the area of surrogate endpoints. In this application, biomarkers act as stand-ins for the effects of a drug on cancer progression and survival. Ideally, the use of validated biomarkers would prevent patients from having to undergo tumor biopsies and lengthy clinical trials to determine if a new drug worked. In the current standard of care, the metric for determining a drug's effectiveness is to check if it has decreased cancer progression in humans and ultimately whether it prolongs survival. However, successful biomarker surrogates could save substantial time, effort, and money if failing drugs could be eliminated from the development pipeline before being brought to clinical trials.

Some ideal characteristics of surrogate endpoint biomarkers include:{{cite journal | vauthors = Price C, McDonnell D | title = Effects of niobium filtration and constant potential on the sensitometric responses of dental radiographic films | journal = Dento Maxillo Facial Radiology | volume = 20 | issue = 1 | pages = 11–16 | date = February 1991 | pmid = 1884846 | doi = 10.1259/dmfr.20.1.1884846 | doi-broken-date = 2024-11-28 }}{{cite journal | vauthors = Cohen V, Khuri FR | title = Progress in lung cancer chemoprevention | journal = Cancer Control | volume = 10 | issue = 4 | pages = 315–324 | year = 2003 | pmid = 12915810 | doi = 10.1177/107327480301000406 | doi-access = free }}

• Biomarker should be involved in process that causes the cancer
• Changes in biomarker should correlate with changes in the disease
• Levels of biomarkers should be high enough that they can be measured easily and reliably
• Levels or presence of biomarker should readily distinguish between normal, cancerous, and precancerous tissue
• Effective treatment of the cancer should change the level of the biomarker
• Level of the biomarker should not change spontaneously or in response to other factors not related to the successful treatment of the cancer

Two areas in particular that are receiving attention as surrogate markers include circulating tumor cells (CTCs){{cite journal | vauthors = Lu CY, Tsai HL, Uen YH, Hu HM, Chen CW, Cheng TL, Lin SR, Wang JY | display-authors = 6 | title = Circulating tumor cells as a surrogate marker for determining clinical outcome to mFOLFOX chemotherapy in patients with stage III colon cancer | journal = British Journal of Cancer | volume = 108 | issue = 4 | pages = 791–797 | date = March 2013 | pmid = 23422758 | pmc = 3590657 | doi = 10.1038/bjc.2012.595 }}{{cite journal | vauthors = Balic M, Williams A, Lin H, Datar R, Cote RJ | title = Circulating tumor cells: from bench to bedside | journal = Annual Review of Medicine | volume = 64 | pages = 31–44 | year = 2013 | pmid = 23092385 | pmc = 3809995 | doi = 10.1146/annurev-med-050311-163404 }} and circulating miRNAs.{{cite journal | vauthors = Madhavan D, Zucknick M, Wallwiener M, Cuk K, Modugno C, Scharpff M, Schott S, Heil J, Turchinovich A, Yang R, Benner A, Riethdorf S, Trumpp A, Sohn C, Pantel K, Schneeweiss A, Burwinkel B | display-authors = 6 | title = Circulating miRNAs as surrogate markers for circulating tumor cells and prognostic markers in metastatic breast cancer | journal = Clinical Cancer Research | volume = 18 | issue = 21 | pages = 5972–5982 | date = November 2012 | pmid = 22952344 | doi = 10.1158/1078-0432.CCR-12-1407 | doi-access = free }}{{cite journal | vauthors = Redova M, Sana J, Slaby O | title = Circulating miRNAs as new blood-based biomarkers for solid cancers | journal = Future Oncology | volume = 9 | issue = 3 | pages = 387–402 | date = March 2013 | pmid = 23469974 | doi = 10.2217/fon.12.192 }} Both these markers are associated with the number of tumor cells present in the blood, and as such, are hoped to provide a surrogate for tumor progression and metastasis. However, significant barriers to their adoption include the difficulty of enriching, identifying, and measuring CTC and miRNA levels in blood. New technologies and research are likely necessary for their translation into clinical care.{{cite journal | vauthors = Joosse SA, Pantel K | title = Biologic challenges in the detection of circulating tumor cells | journal = Cancer Research | volume = 73 | issue = 1 | pages = 8–11 | date = January 2013 | pmid = 23271724 | doi = 10.1158/0008-5472.CAN-12-3422 | doi-access = free }}{{cite journal | vauthors = Hou HW, Warkiani ME, Khoo BL, Li ZR, Soo RA, Tan DS, Lim WT, Han J, Bhagat AA, Lim CT | display-authors = 6 | title = Isolation and retrieval of circulating tumor cells using centrifugal forces | journal = Scientific Reports | volume = 3 | pages = 1259 | year = 2013 | pmid = 23405273 | pmc = 3569917 | doi = 10.1038/srep01259 | bibcode = 2013NatSR...3.1259H }}{{cite journal | vauthors = Dhondt B, De Bleser E, Claeys T, Buelens S, Lumen N, Vandesompele J, Beckers A, Fonteyne V, Van der Eecken K, De Bruycker A, Paul J, Gramme P, Ost P | display-authors = 6 | title = Discovery and validation of a serum microRNA signature to characterize oligo- and polymetastatic prostate cancer: not ready for prime time | journal = World Journal of Urology | volume = 37 | issue = 12 | pages = 2557–2564 | date = December 2019 | pmid = 30578441 | doi = 10.1007/s00345-018-2609-8 | s2cid = 58594673 | hdl = 1854/LU-8586484 }}

Other examples of biomarkers:

• Tumor suppressors lost in cancer
• Examples: BRCA1, BRCA2
• RNA
• Examples: mRNA, microRNA{{cite journal | vauthors = Bartels CL, Tsongalis GJ | title = MicroRNAs: novel biomarkers for human cancer | journal = Clinical Chemistry | volume = 55 | issue = 4 | pages = 623–631 | date = April 2009 | pmid = 19246618 | doi = 10.1373/clinchem.2008.112805 | doi-access = free }}
• Proteins found in body fluids or tissue.
• Examples: Prostate-specific antigen, and CA-125
• Antibodies to cancer antigens
• Examples: Merkel cell polyomavirus{{cite journal | vauthors = Paulson KG, Lewis CW, Redman MW, Simonson WT, Lisberg A, Ritter D, Morishima C, Hutchinson K, Mudgistratova L, Blom A, Iyer J, Moshiri AS, Tarabadkar ES, Carter JJ, Bhatia S, Kawasumi M, Galloway DA, Wener MH, Nghiem P | display-authors = 6 | title = Viral oncoprotein antibodies as a marker for recurrence of Merkel cell carcinoma: A prospective validation study | journal = Cancer | volume = 123 | issue = 8 | pages = 1464–1474 | date = April 2017 | pmid = 27925665 | pmc = 5384867 | doi = 10.1002/cncr.30475 }}
• DNA
• Examples: Circulating Tumor DNA (ctDNA)

Not all cancer biomarkers have to be specific to types of cancer. Some biomarkers found in the circulatory system can be used to determine an abnormal growth of cells present in the body. All these types of biomarkers can be identified through diagnostic blood tests, which is one of the main reasons to get regularly health tested. By getting regularly tested, many health issues such as cancer can be discovered at an early stage, preventing many deaths.

The neutrophil-to-lymphocyte ratio has been shown to be a non-specific determinant for many cancers. This ratio focuses on the activity of two components of the immune system that are involved in inflammatory response which is shown to be higher in presence of malignant tumors.{{cite journal | vauthors = Proctor MJ, McMillan DC, Morrison DS, Fletcher CD, Horgan PG, Clarke SJ | title = A derived neutrophil to lymphocyte ratio predicts survival in patients with cancer | journal = British Journal of Cancer | volume = 107 | issue = 4 | pages = 695–699 | date = August 2012 | pmid = 22828611 | pmc = 3419948 | doi = 10.1038/bjc.2012.292 | doi-access = free }} Additionally, basic fibroblast growth factor (bFGF) is a protein that is involved in the proliferation of cells. Unfortunately, it has been shown that in the presence of tumors it is highly active which has led to the conclusion that it may help malignant cells reproduce at faster rates.{{cite journal | vauthors = Liu M, Xing LQ | title = Basic fibroblast growth factor as a potential biomarker for diagnosing malignant tumor metastasis in women | journal = Oncology Letters | volume = 14 | issue = 2 | pages = 1561–1567 | date = August 2017 | pmid = 28789380 | pmc = 5529833 | doi = 10.3892/ol.2017.6335 | doi-access = free }} Research has shown that anti-bFGF antibodies can be used to help treat tumors from many origins. Moreover, insulin-like growth factor (IGF-R) is involved in cell proliferation and growth. It has is possible that it is involved in inhibiting apoptosis, programmed cell death due to some defect.{{cite journal | vauthors = Fürstenberger G, Senn HJ | title = Insulin-like growth factors and cancer | journal = The Lancet. Oncology | volume = 3 | issue = 5 | pages = 298–302 | date = May 2002 | pmid = 12067807 | doi = 10.1016/s1470-2045(02)00731-3 }} Due to this, the levels of IGF-R can be increased when cancer such as breast, prostate, lung, and colorectum is present.{{cite journal | vauthors = Yu H, Rohan T | title = Role of the insulin-like growth factor family in cancer development and progression | journal = Journal of the National Cancer Institute | volume = 92 | issue = 18 | pages = 1472–1489 | date = September 2000 | pmid = 10995803 | doi = 10.1093/jnci/92.18.1472 | doi-access = free }}

• Tumor marker

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Category:Oncology

Category:Biomarkers