Drexel Medicine Researchers Develop New Technology to Target DNA Damage Repair in Cancer Patients
A team of Drexel University College of Medicine researchers is advancing a way to destroy cancer cells exploiting “synthetic lethality,” which is caused by deficiency in the DNA damage response (DDR) pathway. Synthetic lethality occurs when deficiencies in each of any two genes can be tolerated by the cell but the combination of these two deficiencies is lethal.
When a cell cannot repair its DNA effectively, it can lead to the onset or growth of cancer in the body. Seeing this breakdown, a team of Drexel University College of Medicine researchers is advancing a way to destroy cancer cells exploiting “synthetic lethality,” which is caused by deficiency in the DNA damage response (DDR) pathway. Synthetic lethality occurs when deficiencies in each of any two genes can be tolerated by the cell but the combination of these two deficiencies is lethal.
By targeting a protein known as RAD52 — which is essential for repair of DNA damage in some types of cancer cells, but not in normal tissues — the researchers have laid the groundwork for a method of inhibiting RAD52, thereby blocking cancer cells’ ability to repair DNA and proliferate, while sparing normal tissues.
The authors say the work is still in early stages, but has potential for personalized, targeted treatments for some cancer types, including breast and ovarian cancers caused by BRCA1 and BRCA2 gene mutations.
The RAD52 program comes from the lab of Alexander Mazin, PhD, a professor in Drexel’s College of Medicine, where they study homologous recombination (HR) in human cells. The HR process most commonly occurs in cells as they repair harmful DNA double-strand breaks, but when it fails, it can lead to cancer, premature aging, or chromosomal abnormalities. Mazin and colleagues recently signed a license agreement with Rain Therapeutics Inc., to further develop RAD52 inhibitors for cancer patients who carry mutations in BRCA1 and BRCA2 genes and in several other genes of the DDR pathway.
“Targeting RAD52 with inhibitors to destroy these cancer cells that have BRCA1 and BRCA2 and other HR gene mutations is a major step forward in development of personalized therapies for these cancers,” said Mazin. “As this work advances, it may lead to more effective therapies and better survival for millions of cancer patients around the world.”
Drexel’s RAD52 inhibitors have shown potential anti-cancer effect in human cells in BRCA1 deficient models.
There are currently no clinical programs that target RAD52, but under the license agreement, Rain Therapeutics Inc. will support continued research at Drexel while performing research in preparation for clinical study. Drexel will also receive compensation from Rain based on the development and commercialization of this technology.
This work was also bolstered by $353,520 in grants from the Coulter-Drexel Translational Research Partnership given to Mazin’s lab since 2016 to develop this technology for licensing. The Coulter-Drexel Translational Research Partnership Program provides funding to promising translational research projects with the goal of moving innovative technologies to clinical application. The program facilitates commercialization by providing mentorship, project management and connections to external partners and sources of capital. Since it started in 2006, the program has bestowed over $10 million in funding to more than 60 technologies.