New chemotherapy can kill all solid tumors in animal trials
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Researchers at City of Hope, one of the largest cancer research and treatment organizations in the United States, published a new study on Wednesday highlighting targeted chemotherapy that appears to annihilate all solid tumors in preclinical research. The treatment consists of taking a protein once thought too challenging for targeted therapy and using it to proliferate cell nuclear antigen (PCNA).
This is according to a press release by the institution.
Cancer-killing pill
So far, the therapy has proven successful in animal models and researchers will soon begin human trials. The new cancer-killing pill, called AOH1996, targets a cancerous variant of PCNA, a protein that, in its mutated form, is critical in DNA replication and repair of all expanding tumors.
"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," Linda Malkas, Ph.D., professor in City of Hope's Department of Molecular Diagnostics and Experimental Therapeutics and the M.T. & B.A. Ahmadinia, Professor in Molecular Oncology, said in the press release.
"Results have been promising. AOH1996 can suppress tumor 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."
Tests conducted thus far in more than 70 cancer cell lines and several normal control cells showed that AOH1996 selectively kills cancer cells by disrupting the normal cell reproductive cycle.
Undruggable
"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," said Long Gu, Ph.D., lead author of the study and an associate research professor in the Department of Molecular Diagnostics and Experimental Therapeutics at Beckman Research Institute of City of Hope.
"We discovered that PCNA is one of the potential causes of increased nucleic acid replication errors in cancer cells. Now that we know the problem area and can inhibit it, we will dig deeper to understand the process to develop more personalized, targeted cancer medicines."
The researchers claim AOH1996 could become a useful tool in combination therapies as well as for the development of new chemotherapeutics. The researchers will now seek to better understand the mechanism of action of this protein to further improve the ongoing clinical trial in humans.
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