A groundbreaking cancer drug has been developed that targets and destroys solid tumours without harming healthy cells.
The molecule targets a protein, proliferating cell nuclear antigen (PCNA), which is crucial for tumour growth and was previously considered “undruggable.”
After two decades of research, scientists at City of Hope Hospital in Los Angeles, California, USA, successfully created the drug, code named AOH1996 in honor of Anna Olivia Healy, a young girl who passed away from childhood cancer in 2005. It has shown promising results in laboratory tests.
This breakthrough offers hope for patients with various types of solid tumors, as it represents a significant advancement in cancer treatment. Laboratory tests on 70 different cancer cell lines, including those from breast, prostate, brain, ovarian, cervical, skin, and lung cancers, demonstrated its effectiveness against all.
The latest study, published in Cell Chemical Biology, revealed the drug’s effectiveness against various cancer cell lines while sparing healthy cells. The next step is to replicate these findings in human trials. A Phase 1 clinical trial is currently underway at City of Hope to evaluate the drug’s safety and efficacy in patients.
Dr. Linda Malkas, a molecular oncologist who leads the research team at City of Hope Hospital, was inspired to develop the drug after meeting Anna’s father. She explained how the molecule selectively disrupts DNA replication and repair in cancer cells, leaving healthy cells unaffected.
“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.’
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.
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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.
Vanguard
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