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A "holy grail" molecule that kills all solid cancer tumors, leaving other cells unaffected, has been developed by scientists.
The team at the City of Hope, one of the largest cancer research and treatment organizations in the United States, made the breakthrough against the proliferating cell nuclear antigen (PCNA) protein.
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A mutated form of PCNA helps cancers to repair and grow. The team have developed a molecule, AOH1996, that targets and kills the mutated PCNA.
PCNA was previously thought too challenging to be a target for therapy but AOH1996 seems to annihilate all solid tumors in preclinical research.
Scientists continue to investigate the mechanisms that make this cancer-stopping pill work in animal models but there is also a Phase 1 clinical trial test ongoing in humans.
The new therapy is the result of 20 years of research and development and targets a cancerous variant of PCNA, a protein that in its mutated form is critical in DNA replication and repair of all expanding tumors.
Dr. Linda Malkas, professor in City of Hope’s Department of Molecular Diagnostics and Experimental Therapeutics and the M.T. & B.A. Ahmadinia Professor in Molecular Oncology leads the team.
She explained how the molecule selectively disrupts DNA replication and repair in cancer cells, leaving healthy cells unaffected.
(Photo by National Cancer Institute via Unsplash )
(Photo by National Cancer Institute via Unsplash )
© Provided by talker
She said: "Most targeted therapies focus on a single pathway, which enables wily cancer to mutate and eventually become resistant.
“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.
“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.”
The study, published in the journal Cell Chemical Biology, claims AOH1996 has been effective in preclinical research treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers
The researchers tested AOH1996 in more than 70 cancer cell lines and several normal control cells.
They found the molecule selectively kills cancer cells by disrupting the normal cell reproductive cycle.
In their research, they found it prevented cells with damaged DNA from dividing and from making a copy of faulty DNA, causing cancer cell death, known as apoptosis but it did not interrupt healthy stem cells.
(Photo by Louis Reed via Unsplash )
(Photo by Louis Reed via Unsplash )
© Provided by talker
Study co-author associate research professor Dr. Long Gu, said: “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.
“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.”
Experiments showed that the investigational pill made cancer cells more susceptible to chemical agents that cause DNA or chromosome damage, hinting that AOH1996 could become a useful tool in combination therapies and new chemotherapeutics.
Another co-author Prof. Daniel Von Hoff added: "City of Hope has world leaders in cancer research. They also have the infrastructure to drive translational drug discovery from the laboratory into the clinic for patients in need.”
As a next step, the researchers will look to better understand the mechanism of action to further improve the ongoing clinical trial in humans.
City of Hope’s groundbreaking translational research history includes developing the technology underlying synthetic human insulin and monoclonal antibodies, which are integral to widely used, lifesaving cancer drugs, such as trastuzumab, rituximab and cetuximab.
AOH1996 is exclusively licensed by City of Hope to RLL, LLC, a biotechnology company that Prof. Malkas co-founded and holds financial interest in.
The post Scientists develop molecule that kills tumors without affecting other cells appeared first on Talker.
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