New drug found to ‘annihilate’ solid cancerous tumours in early studies
The drug, AOH1996, was named after a little girl, Anna Olivia Healy, who died from neuroblastoma.
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Your support makes all the difference.A new “cancer-stopping” drug has been found to “annihilate” solid cancerous tumours in early stage studies.
The chemotherapy drug leaves healthy cells unaffected, scientists said.
The AOH1996 drug was named after a child – Anna Olivia Healy, born in 1996 – who died when she was only nine after being diagnosed with a rare childhood cancer neuroblastoma.
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
Professor Linda Malkas and her team spent two decades developing the drug that targets a protein in all cancers — including the cancer that led to Anna’s death.
The protein, proliferating cell nuclear antigen (PCNA), was once thought too challenging to aim targeted therapies at.
PCNA in its mutated form encourages tumours to grow by aiding DNA replication and repair of cancerous cells.
Prof Malkas and her team at the City of Hope in California, one of the United States’ largest cancer research and treatment organisations, said their targeted chemotherapy appears to “annihilate” all solid tumours in preclinical research.
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
AOH1996 was tested in more than 70 cell lines and was found to selectively kills cancer cells by disrupting the normal cell reproductive cycle, but it did not interrupt the reproductive cycle of healthy stem cells.
Pre-clinical studies suggest the drug has been shown to be effective in treating cells derived from breast, prostate, brain, ovarian, cervical, skin and lung cancers.
The drug still needs to go through rigorous safety and efficacy testing and large-scale clinical trials before it can be used widely.
But the first patient received the potentially cancer-stopping pill in October with the phase one clinical trial still ongoing and expected to last for at least two years.
Patients are still being recruited to the trial.
Researchers are also still examining mechanisms that make the drug work in animal studies.
Prof Malkas said: “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.”
The professor called the results “promising” but made clear that research has only found AOH1996 can suppress tumour growth in cell and animal models.
Lead author of the study, 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.”
If successful, this drug would be revolutionary for people with cancer
Commenting on the study, Dr Rupal Mistry, senior research information manager at Cancer Research UK, said: “Cancer cells are known for their unpredictability; they can rapidly produce many copies of themselves and even evolve resistance to treatments.
“Targeting the essential mechanisms which allow them to do this is an excellent way to stop cancer cells from growing, but this can be difficult.
“PCNA is a promising target because it is critical for cell growth. And in cancer, PCNA exists in a unique form that could be targeted with this potential new drug while leaving healthy cells unharmed.
“This is important because it could minimise side effects for patients while still providing a powerful treatment against cancer.
“If successful, this drug would be revolutionary for people with cancer. However, research is still in the early stages and more work still needs to be done to understand the response in humans.”
Dorothy Bennett, professor of cell biology at St George’s, University of London, said: “This paper is interesting for investigating a relatively novel approach to selective targeting of cancer cells, via the protein target PCNA, which functions in resolving clashes between replication of DNA and transcription (reading the code).
“The support for the claim in the paper that their lead anti-PCNA agent AOH1996 “kills cancer cells” appears somewhat limited, disappointingly.
“On the positive side, there appears to be broad evidence here for retardation of growth (in vitro) of many human cancer cell lines of various types by this agent, with little damage to several normal cell types, suggesting that this kind of approach deserves further development.”
The study – titled Small Molecule Targeting of Transcription-Replication Conflict for Selective Chemotherapy – was published in the Cell Chemical Biology journal.