Tapping into the Power of Genetics

What if, instead of a mastectomy, you could have less invasive cancer treatment tailored to your own personal genetic makeup? What if you were able to know the odds of finding healthy eggs before undergoing a fertility procedure? DNA may be the key.

In the ever-evolving field of women’s health, researchers are learning just how powerful the ability to tap into human genetics can be.

Looking Back to Move Forward

Dr. Aleksander Rajkovic

In the past, efforts to treat breast and other cancers have largely focused on accurately diagnosing cancer and other diseases. With recent shifts in medical research however, medicine is refocusing to look at the management of genetic diseases, including developing new therapies and approaches to treatment. Precision medicine—where medical researchers and professionals diagnose the genetic makeup of an individual and tailor therapies based on that information—is just one of the approaches born from this transition and it’s being studied right here in Pittsburgh.

Rather than having no choice but to turn to a mastectomy once a woman has been diagnosed with breast cancer, precision medicine prioritizes understanding the development of cancer and the application of medicine and less extreme treatment. It’s the study of genetics and the sequencing of DNA that allows researchers like Dr. Aleksandar Rajkovic, primary investigator at Magee-Womens Research Institute, to individualize treatments based on a patient’s specific genetic makeup and change the way cancer treatment is delivered.

Identifying Mutations Early

The tie between genes and heredity is a common notion, but not all genetic changes are inherited. Genes change over time, and for any number of internal or external reasons, making continual study of an individual’s genetics crucial for understanding how personal genetics impact cancer development and treatment. “A lot of the genetic changes that you find in tumors are not the same as genetic changes that individuals carry overall in their gametes or other organs; they’re not transmitted from generation to generation,” says Dr. Rajkovic.

Diagnosing and treating breast and other cancers is still a critical component of providing care for women, however shining the light on genetics earlier can help eliminate the need to jump to invasive and/or otherwise toxic procedures like chemotherapy, as well as other potential risks related to that particular tumor’s genetic makeup. “A lot of the genes that are involved in breast cancer, like BRCA1 and BRCA2, also indicate an increased risk or predisposition for ovarian cancer,” says Dr. Rajkovic. By diagnosing individuals at risk before any sign of illness, either through sequencing their blood or their tumors, researchers can give doctors the tools they need to provide the most forward-thinking, and potentially preventative, treatment possible.

Some studies have suggested that identifying mutations in certain genes may affect therapies to treat these conditions, but the research is still in its infancy. “By sequencing tumors and comparing the results to non-tumor tissues, scientists can potentially identify not only those at risk, but also the genetic changes that occur in a tumor that can make that tumor better prone to certain therapies,” says Dr. Rajkovic.

Genetic Russian Roulette

Though scientists are making strides in identifying the connection between genetics and cancer-causing mutations, the ever-changing nature of genetics adds a dimension of difficulty. It’s not uncommon for humans to undergo genetic changes throughout their lifetime, such as those that occur in a woman’s reproductive tract during the onset of menstruation. But with continuous genetic activity, however, errors are bound to occur.

In the case of genes, an error during cell division means the potential for mutation—a tumor. “One somewhat controversial theory,” Dr. Rajkovic notes, “is that these genetic errors are like Russian roulette—they simply happen by chance, without any clear or underlying external events.” On the other hand, there are also epidemiologic studies that show a number of associations between mutations and external factors, such as consumption of alcohol, cigarette smoking, or living in areas in close proximity to chemical facilities.

It is likely that both cases are true to a certain degree, but the implications of inherent and external factors are still being analyzed. What does this mean for genetic researchers like Dr. Rajkovic?

In the case of genetic testing for breast cancer, that is, looking primarily at the genes BRCA1 and BCRA2, only two of 20,000 genes are targeted for testing. Yet no gene, just like no human, lives in isolation. Interactions are very important in how any organ functions—the breast, the ovaries, etc.

Dr. Rajkovic notes the importance of looking at additional genes and interactions for more comprehensive information. “Many other genes modify the action of BRCA1 and BRCA2 and some of those genes are already being tested in various gene panels (like the gene known as TP53—a gene that acts as a tumor suppressor). There are still a lot of other genes that we don’t know as much about in regards to the interaction and/or influence related to cancer. We do know, however, that BRCA1 and BRCA2 mutations by themselves are not always sufficient to cause the problem.”

The Fate of Funding

While ideas like precision medicine have taken the medical world by storm, much of the research into the use of genetics for the treatment and prevention of breast cancer and reproductive diseases is still ongoing. While researchers like Dr. Rajkovic have high hopes for the potential outcomes of such studies, there is one looming fear: “What is scary is the fact that NIH funding might be cut. If that happens, there will be significantly less funding into [the area of cancer and reproductive genetics] and that could decelerate the progress to find clinical utility and be more precise in the way we treat tumors.” Without funding, the ability to find new genetic-based treatments for cancer will be significantly stunted.

Genetics impacts nearly all processes related to reproduction and even plays a significant role in understanding multiple types of cancer. The ability to study variations in human genetics that can lead to manifestations of different diseases such as ovarian cancer, uterine fibroids, even ovarian development, is incredibly important in finding ways to prevent them. While it’s not going to happen overnight, with significant time and investment, researchers like Dr. Rajkovic are determined to unlock the full potential of genetics in the fight against cancer.

You can help researchers like Dr. Rajkovic find new treatments for breast and ovarian cancer patients. Support medical research and donate to Magee-Womens Research Institute today