cancer, seeking to uncover new genetic causes of the disease. Through a pilot project, Cooper’s lab analyzed the genomes of ten individuals with a strong family (and personal) history of cancer but negative results from standard genetic testing. They used whole-genome sequencing to look at all of the DNA in a person’s genome rather than just a few regions already known to be involved in cancer. Using this approach, Cooper’s team aimed to identify rare variants that could explain the high incidence of cancer in these families. Initially, the researchers focused on rare coding variants in known cancer risk genes. Their initial analysis led them to ask whether other regions of the genetic landscape should be further considered. They shifted their attention to non- coding regulatory sequences and splicing variants, which can also play a role in gene expression and function.
The analysis of this data is still ongoing, but the team hopes to find new genetic contributors to early hereditary cancers that can help individuals gain a more complete picture of their cancer risk. GENETIC MECHANISMS OF CHEMOTHERAPY RESISTANCE Being diagnosed with cancer is often just the beginning of a long journey for many individuals. Receiving the right treatment for your cancer can be difficult, with many patients undergoing com- binations of different drugs or switching from one therapy to another. Still, others face the challeng- ing obstacle of their cancer becoming resistant to a treatment that was previously working well for them. This phenomenon, called chemotherapy resistance, is a growing problem in treating cancer and leads to higher mortality in some cancers. Dr. Cooper’s lab wants to understand the mechanisms behind chemotherapy resistance in certain types of cancer, especially those with a high incidence of resistance, like pancreatic and ovarian cancers. To help identify the genetic basis of che- motherapy resistance, the lab uses the gene-editing tool CRISPR to identify genes that contribute to resistance to common chemotherapy drugs. They’ve had success with this method in pancreatic cancer. In a study published in BMC Cancer , Cooper’s lab identified a genetic variant in the ANGPTL4 gene that is associated with chemo- therapy resistance 1 . Overexpression of the gene was found to protect cancer cells from chemotherapy. Cooper’s lab is now applying the same tech- nology to ovarian cancer cells. They have already identified several genes involved in chemotherapy resistance, many of which are related to cell prolif- eration and cell-cell interactions. The next step in this research is to explore the complex interplay between tumor cells and the immune system. By understanding how these interactions contribute to cancer progression and treatment response, researchers can develop more targeted and effective therapies. Ultimately, Dr. Cooper’s research goal is to use genetic information to predict patient response to different treatments, develop personalized treat- ments, and improve patient outcomes. ■
The more we can uncover about genetic changes that contribute to cancer, the more personalized diagnostics and treatments we can develop, increasing the chances of successful treatments.
—sara cooper, PHD
To learn more, listen to
RESEARCH REPORT 2023-2024
27
Made with FlippingBook - Online magazine maker