Researchers at City of Hope — one of the largest cancer research & treatment organizations in the U.S. — discovered a revolutionary, ‘cancer-killing’ drug called AOH1996. Essentially, they took a protein once thought to be too challenging for targeted therapy, proliferating cell nuclear antigen (PCNA), and developed targeted chemotherapy that effectively destroys all solid tumors in preclinical research.
Currently, they’re undergoing ongoing Phase 1 clinical trial testing AOH1996 in humans.
What Makes AOH1996 Different?
Most targeted therapies focus on a single pathway – enabling wily cancer to mutate and eventually become resistant. However, AOH1996 targets a cancerous variant of PCNA (the protein which, in its mutated form, is necessary for the DNA replication and repair of cancerous tumors).
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, told Cell Chemical Biology that “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.”
Is It Working?
In a nutshell, the results have been promising. AOH1996 effectively suppresses tumor growth as a monotherapy or combination treatment in cell and animal models without resulting in toxicity. And as we mentioned, the investigational chemotherapeutic is currently in Phase 1 clinical trial in humans at City of Hope.
So far, AOH1996 has effectively treated cells derived from breast, prostate, brain, ovarian, cervical, skin, and lung cancers. And it’s exclusively licensed by the City of Hope.
How Does AOH1996 Work?
AOH1996 selectively kills cancer cells by disrupting their normal reproductive cycle. It targets something called transcription replication conflicts – which occur when mechanisms responsible for gene expression and genome duplication collide. Essentially, the drug prevents cells with damaged DNA from dividing and making copies of faulty DNA. As a result, it effectively destroys cancer cells without interrupting the reproductive cycle of healthy cells
Previously, PCNA was considered ‘undruggable,’ which is why no one had targeted it before. However, research reveals that PCNA is one of the potential causes of increased nucleic acid replication errors in cancer cells. And now that we know that, researchers can develop more personalized, targeted cancer medicines.
Additionally, research reveals that AOH1996 made cancerous cells more susceptible to chemical agents causing DNA or chromosomal damage. Therefore, it could become a useful tool in combination therapies, as well as for the development of new chemotherapeutics.
Who Is Eligible?
As we mentioned, researchers are improving the ongoing clinical trial in humans. Therefore, interested individuals in the Phase 1 clinical trial should review the eligibility requirements at clinicaltrials.gov. Then, call 626-218-1133 or visit the City of Hope’s clinical trials webpage if eligible.
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