A ‘groundbreaking’ molecule that kills all solid cancer tumors and leaves other cells unaffected has been developed by scientists.
The team at the City of Hope, one of America’s largest cancer research and treatment organizations, has created a drug targeting a protein present in most cancers and helps them multiply in the body.
It is significant because this protein was previously thought to be ‘undruggable’ due to its structural and functional features, which made it a difficult target for drug development.
The investigational chemotherapeutic is currently being tested on humans in a Phase 1 clinical trial in humans at City of Hope, and scientists are still trying to investigate precisely how the cancer-stopping pill works.
Curing cancer has been a key goal of Biden’s — with his relaunched Cancer Moonshot operation in 2022 aiming to reduce the cancer death rate by half in the next 25 years. He claimed last week that his administration had ‘ended cancer as we know it’.
The researchers found the pill 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
The new therapy comes from 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, which helps cancers to repair and grow.
The team has developed a molecule, AOH1996, that targets and kills the mutated PCNA. The treatment seems to annihilate all solid tumors in preclinical research.
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.
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.’
Dr Malkas said results so far have been ‘promising’ as the molecule can suppress tumor growth on its own or in combination with other cancer treatments ‘without resulting in toxicity.’
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.
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 be helpful 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 understand the mechanism of action better 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.
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