Advances in genetics and genetics reimagining cancer patient care
Both genetics and genomics are important topics in biology and have become somewhat familiar terms, but what do they mean? How can genetics and genomics-related technologies help improve the care of patients today, including those with cancer?
To discuss these and more, CRI Broad, PhD, of the CRI Broad Institute of MIT and the Harvard and Angiosarcoma Project. And he spoke with Elizar von Allen, MD of Harvard Medical School and the Dana-Farber Cancer Institute. Cancer Research Institute (CRI) as part of the “Cancer Immunotherapy and You” webinar series on patient education. This is something that is so clearly stated that it is confusing and complicated and the words used are not always well understood.
Generally, genetics is used to describe the genes you inherit from your parents. It is also known as the germline, and every cell in the body begins with the same copy. Over time, the genes in some cells can change from random DNA repair errors to exposure to agents that alter DNA, such as ultraviolet (UV) radiation, cigarette smoke, and other carcinogens.
Genetics is the study of changes in the genes of living cells. In the case of cancer, it is the analysis of mutated genes from tumor cells. (These changes in living cells are also called somatic mutations.) Therefore, genetic testing or genetic sequencing has the potential to provide clinicians with important information and enable them to provide better care for their patients. With genetic testing, doctors can find out how many mutations are in the tumor. This is called mutual tumor burden or TMB. Doctors can also tell if a tumor has become unstable or has an “MSI-H” status based on the presence of high microsatellite instability, which means it has several genetic defects.
Both TMB-H and MSI-H tumors are susceptible to immunotherapy, and the FDA has already issued two immunotherapy approvals for all advanced cancers with these genetic markers, regardless of the organ from which they originate. The reason immunotherapy works so well against these tumors is that they generally appear more “foreign” to the immune system due to their mutations.
In particular, as Van Allen pointed out, the absence of these biomarkers (TMB-H or MSI-H) in a patient’s tumor does not mean that it does not respond to immunotherapy. These are not accurate biomarkers, but many are unknown to us, so continued clinical research is crucial.
Scientists are busy searching for other significant genetic tests beyond TMB-H and MSI-H status. Very different mutations are found in different patients and are as important as driving tumor growth and survival or providing targets for the immune system or knowing which mutations are just bystanders. It is clear that certain genetic changes called “events” can occur after treatment and that the changes can be important to a further treatment decision. There are currently enough drugs for specific genetic mutations (theoretically they can be found in every cancer), suggesting that they may provide clinical value.
Additionally, these tools can also initiate the identification of specific mutations to develop cell therapies and vaccines that can be customized for individual patients. New tools are also being developed to improve the tumor gene analysis process.
Liquid biopsies are a good procedure, the painter explained, “which is a wonderful way of saying a blood draw.” Both normal cells and tumor cells can “shed” the DNA that leads to circulation in the blood, and this material can be analyzed by blood biopsies. Cell-free DNA, or cfDNA, represents this DNA, while cancer-related DNA is called circulating tumor DNA, or ctDNA.
This non-invasive biopsy method, when confirmed, allows physicians to monitor patient tumors more quickly and easily without the need for a surgical biopsy. It also facilitates multiple examinations over time in patients with advanced, refractory cancer. Finally, liquid biopsies provide the ability to analyze DNA from tumors at different locations in people with metastatic disease.
They are both Drs. Painter and Van Allen also emphasized the need for more data to further optimize these approaches and our understanding of genetic testing in general and to help the patient community make significant progress here.
Unlike tumor genetics, genetics that focuses on genes you inherit from your parents can help patients better understand cancer risk and be particularly informative in families or others with a history of cancer. Known genetic risk factors.
Certain BRCA gene variants or some inherited genetic factors associated with Lynch syndrome increase a person’s risk of cancer throughout life. The presence of some of these also indicates when a person is developing cancer and is likely to respond to a specific therapeutic intervention. Painter, who has a brush with cancer, has also solved some of the real problems some patients have with their test kits, perhaps allowing others to access information about their DNA.
In particular, he discussed privacy concerns and concerns that may arise from it. Finally, she stressed the importance of talking to people, and really digging into their medical team, about what tests are right for them. She encouraged patients to speak with genetic counsellors if possible. Trained geneticists can be very helpful in navigating and trying to understand the risks of the various options available to one. These decisions are very personal and completely personal in nature.
For more information on genomic sequencing for patients, see Sequence Me. More information on genetic testing and counselling can be found through the National Society of Genetic Counselors.