Q: Why should I consider genetic testing?
A: Cancer is a genetic disease, caused by one or more mutations in DNA that results in uncontrolled cell growth. As cancer cells divide, they accumulate many additional mutations. Many of these mutations will have no effect, but some may provide the cancer with the ability to evade certain therapies (i.e., treatment resistance) and others may create vulnerabilities to certain therapies (sensitizing mutations). In addition, the natural variation in our DNA that we are born with also may predispose us to respond, display resistance, or display toxicity to certain medications. Genetic testing has the ability to determine if you have genetic variation or tumor mutations that may impact your response to medications. However, not all genetic tests are created equal, and Clarified Precision Medicine can help you determine the test or tests that are most appropriate for you.
Q: How can Clarified Precision Medicine™ help?
A: Clarified Precision Medicine specializes in providing therapeutic guidance based on information obtained from any or all of the genetic tests described here. In some patients, genetic tests will report multiple viable treatment options. The expert precision medicine review provided by Clarified Precision Medicine can help identify which therapies are best among the candidates. In addition, Clarified Precision Medicine can provide information regarding which clinical trials are most suitable given the genetic profile of the patient.
Q: What are the different types of genetic tests available to me?
A: What is comprehensive genomic profiling?
Q: What is comprehensive genomic profiling (CGP)?
A: CGP measures a wide range of genetic mutations, including single nucleotide variation, indels, copy number variations, fusions, and splice variants. These tests are performed directly on the cancer cells, which means they require a tissue sample from the tumor or some tests are now able to use a blood sample from which they can obtain DNA from circulating tumor cells (ctDNA).
These tests may detect an acquired mutation that promotes cancerous or neoplastic activity (activating mutation) in the cell. A CGP test has the ability to detect these mutations and combined with a ClarifiedSelect report, we can recommend a medication that can exploit this mutation, if available.
Although not available from all test providers, CGP has the added benefit of providing immunotherapy biomarkers, such as tumor mutational burden (TMB) and microsatellite instability (MSI). These markers can be useful for determining your likelihood to responding to a class of medications called immune checkpoint inhibitors. In this case, having an elevated TMB (TMB >10 mut/Mb) or having high MSI does not guarantee that you will respond to these medications, but suggests that you may be more likely to have a good response.
Unlike the other genetic tests described below, patients can benefit from multiple CGP tests over time. Because cancers continuously gain new mutations as the divide, and treatments put added pressure on cancer cells to develop mutations that allow them to evade treatment, the original CGP test you obtained my not be an accurate representation of your tumor at later stages of treatment.
Q: What is a pharmacogenomics (PGx) test?
A: PGx profiling measures variation in your DNA that may make you more or less responsive to certain medications, or in some case be more susceptible to adverse side effects. For this test, non-cancerous cells are needed, and samples can be obtained from a variety of biospecimens, such as blood, skin, or saliva.
PGx profiling can provide information such as how rapidly you will metabolize a medication (i.e., process and eliminate it from your body). This information can sometimes be used to determine whether you may need a higher or lower dose to get the optimal response tailored to you. In addition, some medications can have dangerous side effects that impact the heart (cardiotoxicity) or the brain and nervous system (neurotoxicity). PGx testing, with an interpretation from a Clarified Precision Medicine OncoGuardian™ report, can provide you and your care provider with the information necessary to assess your risk of medication side effects, and to make the most informed decisions regarding your choice of treatment.
Q: What is a germline genetic test?
A: Similar to PGx profiling, germline genetic testing is performed on non-cancerous cells. These tests are used to assess your hereditary risk of developing certain cancers. These tests can help to determine if you need to undergo testing or screening more frequently due to your risk of developing a certain type or several types of cancer. Common examples, include inherited mutations in the BRCA1 or BRAC2 gene, which predispose individuals harboring those mutations for developing breast, ovarian, prostate, and other cancer types. Although germline genetic testing can sometimes provide information useful in making treatment decisions, its primary utility is in identifying individuals at risk so that they can be monitored more closely with the goals of catching the cancer in an early stage when curative treatment is possible.