Can we stop cancer cells from evolving and developing drug resistance? British scientists take a leaf out of the HIV playbook
British scientists want to counter cancer by using an approach that worked for HIV and tuberculosis: by creating treatments to preclude cancer’s ability to become resistant to existing drugs and recur.
The drug discovery program, orchestrated by the Institute of Cancer Research (ICR) in London, will be launched at a facility in the British capital with an initial £75 million (roughly $85 million) injection.
Despite the advent of immunotherapies in the cancer therapeutic arsenal, the issue of resistance to cancer drugs — including chemotherapies and molecular-targeted therapies — is rampant. For example, the classic approach of employing aggressive ‘shock and awe’ chemotherapy can falter because too often it helps fuel an ‘survival of the nastiest’ evolution among cancer cells, ICR scientists contend.
ICR intends to address the challenge on two fronts. First, is an approach called ‘evolutionary herding’. Using artificial intelligence, researchers at ICR can forecast how cancer cells tend to react when treated with a particular drug. Therefore by selecting an initial drug treatment — cancer cells can be compelled to adapt in a fashion that makes them susceptible to a secondary treatment, or thrusts them into an “evolutionary dead end”.
The second strategy is to develop a family of drugs that thwart the ability of cancer cells to evolve and resist treatment. This fresh class of drugs are being constructed to target a protein called APOBEC in a bid to diminish the rate of mutation in cancer cells, slow down evolution and delay resistance. Although the enzyme is crucial for the immune system to adapt to different infectious diseases, it has been implicated in cancer mutations recently, after being the focus of virology research for over a decade.
Once developed, these APOBEC inhibitors could be administered in tandem with existing targeted oncology therapies to keep the cancer at bay for longer periods, or indeed elevate it to the position of a chronic disease from an often incurable diagnosis.
“We believe this will be the first treatment in the world that rather than dealing with the consequences of cancer’s evolution and resistance, aims to directly confront the disease’s ability to adapt and evolve in the first place,” said Olivia Rossanese, who will serve as head of biology at the new ICR facility, in a statement.
Another approach touted by ICR is combining cancer drugs to combat drug resistance. In the lab, ICR researchers have observed that bowel cancer cells evolved to resist two targeted treatments, but succumbed to the third, they said on Wednesday.