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In a major breakthrough in cancer research, scientists have identified a protein that, when targeted, could potentially reverse resistance to platinum-based chemotherapy in cancer cells. The discovery offers hope for patients with cisplatin-resistant cancers, paving the way for more effective treatment options.
Published today in Cancer Research, a journal of the American Association for Cancer Research, the study sheds light on the role of the protein puromycin-sensitive aminopeptidase (NPEPPS) in regulating the response to platinum chemotherapy in patients with bladder cancer.
Lead author James Costello, PhD, an associate professor at the University of Colorado Anschutz Medical Campus, explains, “We found that this protein is a driver in resistance to platinum therapy. If we remove it experimentally or pharmacologically, we can re-sensitize the cancer cells to their pre-resistant level of response.”
For over 45 years, platinum-based drugs like cisplatin have been a cornerstone in cancer treatment due to their efficacy in targeting rapidly growing cancer cells. However, their non-targeted nature often leads to debilitating side effects, rendering some patients ineligible for treatment.
The research team, including co-corresponding author Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer, conducted a comprehensive study to understand why many bladder cancer patients fail to respond well to platinum-based regimens.
Through genetic manipulation of NPEPPS and utilizing patient-derived bladder cancer samples, researchers demonstrated that targeting NPEPPS could enhance the responsiveness of cancer cells to platinum drugs.
“This novel therapeutic approach could allow the administration of lower platinum drug doses, potentially decreasing debilitating side effects while also making platinum-based therapies more effective,” says Costello.
Dr. Theodorescu underscores the significance of precision medicine in revolutionizing cancer treatment, emphasizing the potential of targeting vulnerabilities like NPEPPS with small molecules in combination with cisplatin.
The findings hold promise not only for bladder cancer patients but also for individuals with other cancer types that utilize platinum-based therapies. The research team aims to expand the application of this approach to various clinical settings, with the ultimate goal of enhancing the effectiveness of platinum-based agents in cancer treatment.
