Researchers at California-based City of Hope, one of the largest cancer research and treatment organisations in the United States, have published a new study explaining how they took a protein once thought to be too challenging for targeted therapy, proliferating cell nuclear antigen (PCNA), and developed a targeted chemotherapy that appears to annihilate all solid tumours in preclinical research.
As the scientists continue to investigate the foundational mechanisms that make this “cancer-stopping pill” work in animal models, there is a Phase 1 clinical trial testing the treatment in humans.
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“Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells,” says Professor Linda Malkas, who has been developing the new drug over the past 20 years.
Most targeted therapies focus on a single pathway, which enables cancers to mutate and eventually become resistant, said Dr Malkas. The ‘cancer-killing’ pill Malkas has been developing over the past two decades, AOH1996, targets a cancerous variant of PCNA, a protein that in its mutated form is critical in DNA replication and repair of all expanding tumours.
“PCNA is like a major airline terminal hub containing multiple plane gates. Data suggests PCNA is uniquely altered in cancer cells, and this fact allowed us to design a drug that targeted only the form of PCNA in cancer cells. Our cancer-killing pill is like a snowstorm that closes a key airline hub, shutting down all flights in and out only in planes carrying cancer cells,” said Malkas, senior author of the new study published in Cell Chemical Biology. “Results have been promising. AOH1996 can suppress tumour growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity. The investigational chemotherapeutic is currently in a Phase 1 clinical trial in humans at City of Hope.”
Research
AOH1996 has been effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers and is exclusively licensed by City of Hope to RLL, LLC, a biotechnology company that Malkas co-founded and holds financial interest in.
