Genetic Interaction Map Helps Determine Choice of Chemotherapy
--Must See--

Bioinformatics Summer Internship 2024 With Hands-On-Training + Project / Dissertation - 30 Days, 3 Months & 6 Months Duration

Genetic Interaction Map Helps Determine Choice of Chemotherapy

Chemotherapy is given to the vast majority of cancer patients and used based on average responses rather than personalized decisions. Limited improvements in survival by the use of chemotherapy also highlight the need to develop drugs and make better use of existing drugs. Furthermore, choosing from multiple possible chemotherapy options can complicate clinical decision making. Therefore, optimizing the use of chemotherapies is a significant and pressing challenge in precision oncology.

While 95 percent of cancer patients receive chemotherapy as part of their treatment, oncologists now have little information to guide their decisions about which of these drugs to use in a given patient.

Now, researchers in this direction, have developed a gene–drug interaction map that could help clinicians prescribe the most effective type of chemotherapy for each cancer patient, based on the tumor’s genetic profile.

The University of California led by Sourav Bandyopadhyay, Ph.D., generated the resource by systematically knocking down each of 625 different DNA repair and cancer-relevant genes in cultured cells, and assessing how the cells responded to a wide range of chemotherapy drugs.

In the course of their study, the team mapped the connections between 625 breast and ovarian

cancer genes and most chemotherapy regimens approved by the FDA. They then performed 80,000 experiments in lab dishes to find the efficacy of chemotherapies against tumor cells and the specific genetic mutations they carry.

“We’re trying to take a systems view of chemotherapy resistance,” Bandyopadhyay said. “With rarer mutations in particular there aren’t enough patients for large clinical trials to be able to identify biomarkers of resistance, but by considering all the different potential genetic factors that have been identified together in one study, we can robustly predict from experiments in laboratory dishes how cancers with different genetic mutations will respond to different treatments.

They first identified 200 genes frequently mutated in breast cancer, 170 linked to ovarian cancer and 134 involved in DNA repair, which often is compromised in many cancers. The team then systematically inactivating each of these cancer-associated genes in healthy human cells in lab conditions and what resulted was 625 different perturbations that mirrored distinct genetic mutations seen in real breast and ovarian cancers.

The resultant map allowed the researchers to accurately predict the responses of multiple human cancer cell lines to different chemotherapy agents based on the cell lines’ genetic profiles and also revealed new genetic factors that appear to determine the response of breast and ovarian tumor cells to common classes of chemotherapy treatment.

“In contrast to most standard genetic screens, this approach provides a quantitative readout that approximates genetic interaction strength and allows for the comparison of responses across many drugs,” the researchers write.

In search of the perfect burger. Serial eater. In her spare time, practises her "Vader Voice". Passionate about dance. Real Weird.