In a significant leap forward for cancer research, a team of U.S. scientists has developed a revolutionary “cancer-killing pill” that targets and destroys solid tumors while sparing healthy cells.
The breakthrough was revealed in a study titled “Small Molecule Targeting of Transcription-Replication Conflict for Selective Chemotherapy,” published in the Cell Chemical Biology journal.
The potential game-changer is a drug called AOH1996, named in memory of Anna Olivia Healey, a young girl who succumbed to neuroblastoma, a rare form of cancer. The drug was developed by senior author of the study, Linda Malkas, a scientist based at the City of Hope, one of the largest cancer research and treatment organizations in the United States. According to the City of Hope, AOH1996 has the potential to “annihilate all solid tumors.”
AOH1996 is unique in its mechanism of action. It targets a cancer-specific variant of a protein called proliferating cell nuclear antigen (PCNA). PCNA plays a critical role in the DNA replication and repair processes of cancerous tumors. “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,” explained Malkas.
Unlike most cancer therapies which focus on a single pathway and risk developing resistance, AOH1996 effectively suppresses tumor growth without discernable side effects, by inhibiting the mutated versions of PCNA. Initial results suggest that it can be used as a standalone treatment or in combination with other treatments, without causing toxicity.
Lead author of the study, Long Gu, elaborated, “No one has ever targeted PCNA as a therapeutic because it was viewed as “undruggable,” but clearly City of Hope was able to develop an investigational medicine for a challenging protein target.” The team discovered that PCNA is a potential cause of increased nucleic acid replication errors in cancer cells. By inhibiting it, they can develop more personalized, targeted cancer medicines.
The researchers also found that AOH1996 sensitizes cancer cells to other chemical agents that damage DNA, like cisplatin, a chemotherapy drug. This could open the door for AOH1996 to be used in combination therapies, as well as pave the way for the development of new chemotherapeutics.
Having shown promise in preclinical trials, AOH1996 is now in Phase 1 human trials.