Cancer discovery could help revitalize non-toxic treatment

Research successfully laid out why immunotherapy treatments that target ovarian, colon and triple-negative breast cancer succeeded in lab tests but failed in human trials.

Petri dishes are pictured in an unknown location in a Cancer Research UK laboratory on an unknown date. (photo credit: CANCER RESEARCH UK/HANDOUT VIA REUTERS)
Petri dishes are pictured in an unknown location in a Cancer Research UK laboratory on an unknown date.
(photo credit: CANCER RESEARCH UK/HANDOUT VIA REUTERS)
Researchers at the University of Virginia have published a new study that could revitalize once-promising treatments that help fight solid cancer tumors, the university announced on Monday.
The research successfully laid out why the immunotherapy treatments targeting ovarian, colon and triple-negative breast cancer, succeeded in lab tests but failed in human trials.
Lead researcher Jogender Tushir-Singh, of the UVA Medical School’s Department of Biochemistry and Molecular Genetics, states that the new findings could help restart human trials after new success in lab models.
“So far, researchers and protein engineers around the globe, including our research group, were focused on super-charging and super-activating tumor cell-death receptor-targeting antibodies in the fight against cancer," said Tushir-Singh. "Here at UVA, we took a comprehensive approach to harness the power of the immune system to create dual-specificity and potentially clinically effective oncologic therapeutics for solid tumors."

“Our findings also have significant potential to improve further the clinical efficacy of currently FDA-approved PD-L1-targeting antibodies in solid tumors, particularly the ones approved for deadly triple-negative breast cancer,” Tushir-Singh added.
Scientists first developed an approach that selectively uses antibodies to target cancer cells surface called death receptor-5 (DR5). The treatment has been successful in clinical trials in the past, effectively reducing tumor size in animal trials.
However, when the treatment reached human clinical trials, "these antibodies consistently failed to improve survival in patients."
Tushir-Singh and his team found that the "anti-DR5 antibody approaches unintentionally triggered biological processes that suppress the body’s immune response," the university explained in a statement, allowing the cancer cells to bypass the treatment and continue growing.
The research shares findings that could restore the efficacy of the treatment by combating the biological process, which has so far proven to be successful in shrinking tumors and improving survival in lab mice.
“We would like to see these strategies in clinical trials, which we strongly believe have huge potential in solid tumors,” Tushir-Singh said. “Our findings are extraordinary: Along with the translational impact, our work also explains, after more than 60 years of research in the field, why most approaches targeting apoptosis [cell death] have not done well in clinical trials and ultimately develop resistance to therapies.”