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23 May, 2024
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Revolutionary cancer drug kills all solid tumors, leaves healthy cells intact

Los Angeles' City of Hope Hospital's 20-year research effort yields hope for universal cancer treatment

Source: Daily Mail

Scientists have developed a holy grail cancer drug that kills all solid cancer tumors while leaving other cells unharmed.

The new molecule - codenamed AOH1996 - targets a protein present in most cancers that helps tumors grow and multiply in the body.

It is significant because this protein - the proliferating cell nuclear antigen (PCNA) - was previously thought to be 'undruggable'.

The drug was tested on 70 different cancer cells in the lab - including those derived from breast, prostate, brain, ovarian, cervical, skin, and lung cancer - and was effective against them all.

The drug is the culmination of 20 years of research and development by the City of Hope Hospital in Los Angeles, one of America's largest cancer centers.

It comes amid excitement that cancer will be curable within the coming decade, a claim that has been made by the scientists who invented the Pfizer Covid vaccine.

Curing cancer has also been a key goal of President Joe Biden — with his relaunched Cancer Moonshot operation in 2022 aiming to reduce the cancer death rate by half in the next 25 years.

But he was slammed last week for claiming that his administration had 'ended cancer as we know it' - even though there are signs death rates are slowing.

The latest study, published in the journal Cell Chemical Biology, revealed that the new drug had been tested on more than 70 cancer cell lines and several normal human cells that did not have cancer but were used as a control.

The molecule selectively killed cancer cells by disrupting their normal reproductive cycle, preventing cells with damaged DNA from dividing, and stopping the replication of faulty DNA.

This combination of factors caused the cancer cells to die without harming healthy cells in the process.

An experimental breast cancer vaccine showing promise in early trials is raising the prospect of eliminating one of the world's biggest killers.

The results will now need to be replicated in people. The drug is currently being tested on humans in a Phase 1 clinical trial at City of Hope.

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 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.

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.

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.

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