Scientists at City of Hope Hospital in Los Angeles have developed a promising cancer drug, AOH1996, that selectively destroys solid tumors while preserving healthy cells. This innovative drug targets the proliferating cell nuclear antigen (PCNA), a protein crucial for tumor growth that was previously considered 'undruggable'.
Targeting PCNA in Cancer Cells
Dr. Linda Malkas, the molecular oncologist leading the research, explained that PCNA plays a vital role in DNA replication and repair and is uniquely altered in cancer cells. AOH1996 selectively targets this cancerous form of PCNA, effectively halting tumor growth. According to Dr. Malkas, the drug's mechanism is akin to "a snowstorm that shuts down flights in and out of an airport hub, but only for planes carrying cancer cells."
Preclinical Efficacy
After two decades of research, AOH1996 has demonstrated significant promise in laboratory tests. The drug has proven effective against 70 different cancer cell lines, including breast, prostate, brain, ovarian, cervical, skin, and lung cancers. The study, published in Cell Chemical Biology, highlights AOH1996’s potential to selectively disrupt cancer cell growth while sparing healthy cells.
Clinical Development and Future Directions
Named in honor of Anna Olivia Healy, who passed away from childhood cancer in 2005, AOH1996 is currently undergoing a Phase 1 clinical trial at City of Hope to evaluate its safety and efficacy in human patients. Initial results have been promising, with the drug working effectively on its own or in combination with other cancer treatments, all without causing harmful toxicity.
Dr. Long Gu, study co-author, noted the prior perception of PCNA as an unattainable drug target. "PCNA was viewed as 'undruggable,' but City of Hope developed an investigational medicine to target this challenging protein," said Dr. Gu. Future research will focus on further investigating the drug's mechanism and its potential in combination therapies, offering renewed hope for more personalized cancer treatments.
