Genetic Tests for Targeted Cancer Therapy

This article was last modified on May 13, 2021

What are genetic tests for targeted cancer therapy?

Genetic tests for targeted cancer therapy detect mutations (changes) in the DNA of cancer cells. Knowing whether the cancer has a particular mutation can help guide the type of treatment that a person receives. The presence or absence of certain mutations can predict who may benefit from certain drugs and who is not likely to respond.

Cancer is the uncontrolled growth of abnormal cells. Multiple factors may contribute to this uncontrolled growth. One such factor is the malfunctioning of proteins involved in controlling cell growth and maturation. The proteins usually malfunction as a result of a mutation in the DNA of the gene that codes for that protein. Some mutations may result in a defective protein that cannot stop cell growth while other mutations may produce a protein with altered function that stimulates cell growth. The net result is unchecked growth and division of these abnormal cells (cancer).

Medical researchers have long studied these changes in genes in order to better understand cancer and to develop drugs to fight it. Their goal has been to create drugs that disrupt a specific step in cancer growth, while doing minimal damage to normal cells. These are called targeted drugs or targeted therapy. What researchers have noted is that specific types of cancer are frequently associated with specific genetic mutations. Not every cancer will have them, but a significant percentage will, and cancers with these mutations usually have a more predictable response to certain drug treatments compared to cancers without these mutations.

These findings have led to two important developments:

Cancer drugs that inhibit or target very specific proteins associated with certain cancers (Two examples are tyrosine kinase inhibitors and epidermal growth factor receptor (EGFR) antibodies.)
Genetic tests to detect the presence of mutations in cancer tissue that tell a healthcare practitioner whether the person being tested is likely to benefit from a specific therapy

Medical researchers continue to explore the genetics of cancer and to look for opportunities to develop new therapies. Additionally, some cancers eventually stop responding to certain therapies and develop resistance to that therapy. Genetic research may offer insights into how resistance to therapy occurs.

Common Questions

Why is this testing important?

Standard treatment for cancer usually involves surgery, chemotherapy, radiation therapy, or some combination of these. Treatment with chemotherapy drugs and radiation aims to slow the growth of cancer, keep it from spreading, and kill any cancerous cells that have spread to other parts of the body (metastasized).

Chemotherapy works by attacking cells that are actively growing and dividing. Radiation therapy kills cancer cells by damaging their genes and preventing them from growing and dividing. Both types of therapy can affect all cells that are growing and dividing, including normal cells. This often leads to harmful side effects, and these treatments require careful adjustment to maximize the killing of cancer cells while minimizing the damage to healthy tissue.

Targeted therapy is a newer type of cancer treatment that offers healthcare practitioners and their patients the opportunity to use a drug that has a greater effect on cancerous tissue, reducing many of the side effects associated with standard therapy. It is based on the fact that the genetic makeup of the cancer cells is different than the normal cells around them. Targeted therapy aims to disrupt specific steps or processes that are somewhat unique to the growth of cancer cells. Testing the cancer cells biopsied from patients prior to initiating drug therapy to determine the cancer’s likely response to certain cancer drugs is a key emerging area of testing.

Targeted cancer drugs are expensive, and they generally only work in patients whose cancer has the genetic makeup that they have been developed to work against. Genetic testing prior to beginning therapy is necessary to match the treatment up with the patients and cancers likely to benefit from them.

Examples of targeted cancer drugs for which tests are available include:

Drugs that bind to receptors on the cell surface and block growth signaling to the cell
Drugs that are small molecules that cross the cell membrane and block the signals for growth at the receptor’s active site

How is genetic testing for targeted cancer therapy used?

These genetic tests are used to help guide treatment for certain cancers. They help to inform a health care practitioner as to whether certain targeted cancer drugs may or may not work.

Genes are the basic units of genetic material, the segments of DNA that usually code for the production of specific proteins. Alterations in DNA are called genetic variants (also polymorphisms or mutations) and occur throughout the population. Variants or mutations are largely inherited and affect all cells, but they can occur later in life, because of exposures to radiation, toxins, or for unknown reasons, and these mutations may result in cancer.

In a variety of cancers, there may be a mutation that leads to an increased amount of a particular protein present in the tumor tissue or to production of a protein that has altered activity. Tumors that have these mutations may tend to grow more aggressively, be more likely to spread (metastasize), and/or may be more resistant to standard chemotherapy. Sometimes, however, the changes in the protein also make the tumors candidates for therapy that targets the changed protein (“targeted therapy”). Genetic tests for cancer therapy detect the mutations that code for these proteins, thus identifying tumors that may be susceptible to targeted therapy.

Conversely, genetic tests may also identify tumors that will not respond to targeted therapy. Certain mutations, when present, make the cancer cells resistant to the drug and targeted therapy will not be used for treatment.

When are the tests ordered?

Testing may be ordered as part of an initial workup of particular cancers or performed on those with certain cancers that are not responding to chemotherapy. It requires a sample of the tumor tissue, and if a sample is available from a previous biopsy used for diagnosis, it can be done on that sample.

The tests are usually performed only once. However, testing may be done more than once if a patient’s tumor progresses while on therapy to see if the tumor has acquired mutations that are resistant to the therapy.

What are some examples of these tests?

Each genetic test for a specific targeted cancer therapy identifies mutations in a single gene, and test results are specific to the gene and the targeted therapies being evaluated.

The table below lists examples of some cancers for which genetic testing may be used to help make decisions about targeted drug therapy.

Type of Cancer	Gene Tested*	Interpretation of Test Result
Breast cancer	Her2/neu	When present, likely response to trastuzumab
Chronic myelogenous leukemia (CML)	ABL1	Nonresponsive to imatinib when mutation(s) present
	BCR-ABL	When present, can be measured periodically to monitor response to targeted drug
Colon cancer	KRAS	When mutation present, likely resistance to tyrosine kinase inhibitor
	BRAF	Poor prognosis when mutation present
Gastrointestinal stromal tumor (GIST)—rare tumors of the digestive tract	KIT	Depending on mutation present, better response to imatinib therapy, increased dose of imatinib likely necessary and better response to sunitinib, or possible resistance to imatinib
	PDGFRA	When mutation present, less likely to respond to imatinib
Melanoma	BRAF	Better response to vemurafenib when mutation present with metastatic melanoma
Myeloproliferative neoplasms (MPNs)	JAK2	When mutation present, may be measured periodically to monitor responsiveness to treatment (e.g., Ruxolitinib)
Non-small cell lung cancer (NSCLC)	EGFR	Best response to tyrosine kinase inhibitors such as gefitinib and erlotinib in those with certain mutations
	EML4-ALK	If ALK is present, may respond to ALK kinase inhibitors, such as crizotinib
	ROS1	If ROS1 is present, ALK kinase inhibitors, such as crizotinib
	KRAS	Poorer prognosis when certain mutations present, resistance to tyrosine kinase inhibitors, and poor response to platinum/vinorelbine therapy
	PDL1	Likely response to immunotherapy
Cancers of unknown origin—cancers detected in unusual body sites and thought to have spread (metastasized) from another location	Several genes evaluated together (genomic array or profile)	Helps determine the organ or body part in which the cancer originated in order to help guide treatment

* Gene names are typically abbreviated for ease of use because full names are often several words long.

Usually, the cancer drugs and genetic tests listed in the table above have been developed concurrently; thus, the tests are referred to as “companion diagnostics.” These are laboratory tests that are developed specifically to “provide information that is essential for the safe and effective use of a corresponding therapeutic product,” according to the U.S. Food and Drug Administration (FDA). In many cases, results from these tests are needed for health care practitioners to be able to make decisions regarding treatment of their patients.

Cancers associated with a strong family history and those that occur at a young age may have different characteristics than those that develop sporadically in adults. For instance, pediatric cases of GIST are very different than adult cases and do not typically have KIT or PDGFRA mutations.

Only common mutations are tested. A negative test result does not rule out the possibility that a person has a less common mutation. To rule out the possibility that the mutation was not present in the sample tested, additional samples may be needed.

Some tests for specific gene mutations in certain types of cancer are available on a limited basis and/or not used routinely for medical purposes. These genetic tests may, however, be used in research settings and their utility in medical care may evolve as research progresses. Some examples include:

Colon cancer: PIK3CA and NRAS
Melanoma: KIT and NRAS
Myeloproliferative neoplasms: PDGFRA

Should everyone with cancer have genetic testing performed?

Testing is only required if a patient has a specific type of cancer for which targeted therapies have been identified as being useful and the health care practitioner is considering starting the patient on one of these therapies.

Can I receive one of these therapies and still not benefit from it?

Yes, most people whose cancer matches up with the “likely to benefit” criteria will respond, but a percentage will not. Each person and each cancer is different.

Can I take a targeted therapy drug without being tested?

In most cases, this is not recommended. The drugs have been developed with specific associations and your cancer is not likely to respond if you do not meet the identified criteria.

Can molecular testing be performed in my healthcare provider's office or my local hospital laboratory?

Testing requires specialized equipment and is not offered by every laboratory. In most cases, samples will be sent to a reference laboratory.

View Sources

Sources Used in Current Review

Mahadevan, D. (2015 November 18 Updated). Targeted Cancer Therapy. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/1372666-overview#showall. Accessed on 9/05/16.

(2013 July 12 Revised). Targeted Cancer Therapy. American Cancer Society. Available online at http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/targetedtherapy/index. Accessed on 9/05/16.

(2014 June 12 Revised). The History of Cancer. American Cancer Society. Available online at http://www.cancer.org/acs/groups/cid/documents/webcontent/002048-pdf.pdf. Accessed on 9/05/16.

(2014 April 25 Reviewed). Targeted Cancer Therapies. National Cancer Institute. Available online at http://www.cancer.gov/about-cancer/treatment/types/targeted-therapies/targeted-therapies-fact-sheet. Accessed on 9/05/16.

Chaturvedi, P. and Wenig, B. (2015 November 23 Updated). Targeted Molecular Therapy in Head and Neck Squamous Cell Carcinoma Overview of Targeted Molecular Therapy in HNSCC. Available online at http://emedicine.medscape.com/article/854971-overview#showall. Accessed on 9/05/16.

Tuazon, S. (2015 September 25 Updated). BRAF Gene Mutation Tests. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/2045309-overview#showall. Accessed on 9/05/16.

Markman, M. (2016 April 26 Updated). Colorectal Cancer and KRAS/BRAF. Medscape Drugs and Diseases. Available online at http://emedicine.medscape.com/article/1690010-overview Accessed on 9/05/16.

(2016 June 09 Updated). List of Cleared or Approved Companion Diagnostic Devices (In Vitro and Imaging Tools). US Food and Drug Administration. Available online at http://www.fda.gov/medicaldevices/productsandmedicalprocedures/invitrodiagnostics/ucm301431.htm. Accessed on 9/14/16.

Cagle, P. et. Al (2016). Emerging Biomarkers in Personalized Therapy of Lung Cancer. Adv Exp Med Biol. 2016;890:25-36. doi: 10.1007/978-3-319-24932-2_2. Abstract. Available online at http://www.ncbi.nlm.nih.gov/pubmed/26703797. Accessed on 9/14/16.

Dietel, M. et al (2015 September). A 2015 update on predictive molecular pathology and its role in targeted cancer therapy: a review focussing on clinical relevance. Cancer Gene Ther. 2015 Sep;22(9):417-30. doi: 10.1038/cgt.2015.39. Epub 2015 Sep 11. Abstract. Available online at https://www.ncbi.nlm.nih.gov/pubmed/26358176/. Accessed on 9/14/16.

Abramson, R. 2016. Overview of Targeted Therapies for Cancer. My Cancer Genome (Updated August 8). Available online at https://www.mycancergenome.org/content/molecular-medicine/overview-of-targeted-therapies-for-cancer. Accessed September 2016.

Sources Used in Previous Reviews

Linnea Baudhuin, Phd, DABMG. Assistant Professor of Laboratory Medicine. Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN.

(Revised 2011 November 18). Targeted Cancer Therapies. National Cancer Institute Fact Sheet [On-line information]. Available online at http://www.cancer.gov/cancertopics/factsheet/Therapy/targeted. Accessed March 2012.

Gaughan, E. and Costa, D. (2011 May 19). Genotype-driven Therapies for Non-small Cell Lung Cancer, Focus on EGFR, KRAS and ALK Gene Abnormalities. Medscape Today News from Ther Adv Med Oncol v 3(3):113-125 [On-line information]. Available online at http://www.medscape.com/viewarticle/742530. Accessed March 2012.

Ribas, A. and Flaherty, K. (2011 July 8). BRAF Targeted Therapy Changes the Treatment Paradigm in Melanoma. Nat Rev Clin Onc. 2011;8(7) © Medscape Today News from Nat Rev Clin Onc. v 8(7) [On-line information]. Available online at http://www.medscape.com/viewarticle/744864. Accessed March 2012.

Mahadevan, D. and Talavera, F. (2011 May 16) Targeted Cancer Therapy. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1372666-overview#showall. Accessed March 2012.

Bayon, R. and Chaturvedi, P. (2011 March 29). Targeted Molecular Therapy in Head and Neck Squamous Cell Carcinoma Overview of Targeted Molecular Therapy in HNSCC. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/854971-overview. Accessed March 2012.

(2009 July/August). KRAS Mutation Testing for Anti-Epidermal Growth Factor Receptor Therapy in Colorectal and Lung Cancer. Mayo Clinic Mayo Medical Laboratory Communique [On-line information]. Available online at http://www.mayomedicallaboratories.com/articles/communique/2009/07.html. Accessed May 2012.

Cankovic, M. et. al. (2009 December 8). Clinical Performance of JAK2 V617F Mutation Detection Assays in a Molecular Diagnostics Laboratory: Evaluation of Screening and Quantitation Methods. American Journal of Clinical Pathology v 132(5):713-721. [On-line information]. Available online at http://www.medscape.com/viewarticle/712654. Accessed March 2012.

(Updated 2011 July 8). Colorectal Cancer Trials Support Gene Testing for Two Drugs. National Cancer Institute Fact Sheet [On-line information]. Available online at http://www.cancer.gov/clinicaltrials/results/summary/2008/genetest1108. Accessed March 2012.

Cheson, B. et. al. (2011 November 23). 2011 Top Game Changers in Oncology. Medscape Today News [On-line information]. Available online at http://www.medscape.com/viewarticle/754136. Accessed March 2012.

Corless, C. et. al. (2011 December 31). Gastrointestinal Stromal Tumours Origin and Molecular Oncology. Medscape Today News from Nat Rev Cancer v 11(12):865-878 [On-line information]. Available online at http://www.medscape.com/viewarticle/754503. Accessed March 2012.

Markman, M. (Updated 2011 November 29). Genetics of Non-Small Cell Lung Cancer. Medscape Reference [On-line information]. Available online at http://emedicine.medscape.com/article/1689988-overview. Accessed March 2012.

Cook, J. et. al. (Updated 2011 July). Gastrointestinal Stromal Tumors – GIST. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/GIST.html?client_ID=LTD. Accessed March 2012.

Lyon, E. et. al. (Updated 2011 July). 5-Fluorouracil Sensitivity. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/5FU.html. Accessed March 2012.

Lyon, E. et. al. (Updated 2011 April). UGT1A1 Genotyping – Irinotecan. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Irinotecan.html. Accessed March 2012.

Turner, J. et. al. (2010 December 17). KRAS Mutation Testing for Colorectal Cancer (CRC). CAP [On-line information]. Available online through http://www.cap.org. Accessed March 2012.

Test ID: FLCA Lung Cancer, ALK (2p23) Rearrangement, FISH, Tissue. Mayo Clinic Mayo Medical Laboratories [On-line information]. Available online at http://www.mayomedicallaboratories.com/test-catalog/Overview/60619. Accessed March 2012.

Lyon, E. et. al. (Updated 2011 April). CYP2D6 Genotyping – Tamoxifen. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/Tamoxifen.html. Accessed March 2012.

Jarboe, E. et. al. (Updated 2011 February). Colorectal Cancer. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/ColorectalCancer.html#tabs=0. Accessed March 2012.

Johnson-Davis, K. and McMillin, G. (Updated 2011 August). Pharmacogenetics – PGx. ARUP Consult [On-line information]. Available online at http://www.arupconsult.com/Topics/PGx.html?client_ID=LTD#tabs=0. Accessed March 2012.

Kelland, K. (2012 March 7). Cancer gene mutation more complex than previously thought: study. MedlinePlus from Reuters Health [On-line information]. Available online at http://www.nlm.nih.gov/medlineplus/news/fullstory_122697.html. Accessed March 2012.

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