Overheating cancer: a new treatment strategy

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Taking on cancer with a revolutionary tactic, researcher Matheus dos Santos Dias and his team are flipping conventional treatment strategies on their head.

Instead of trying to slow down or stop cancer cells, they’re looking to push them into overdrive until they essentially self-destruct.

This novel approach, which initially faced skepticism, is based on the idea that you can fight cancer not just by holding it back but by pushing it to its limits.

Typically, cancer treatments aim to inhibit the processes cancer cells rely on for rapid division, trying to curb the growth of the tumor. However, cancer is notoriously cunning, often finding ways to bypass these inhibitions, leading to treatments becoming ineffective.

Dos Santos Dias’ strategy, however, embraces the opposite tactic: overstimulating the cancer cells to exhaust them beyond recovery.

The method involves a two-step process with a pair of drugs: one that stimulates the cancer cells and another that cuts off their escape routes.

By doing this, the balance within the cancer cells is disrupted to a point of no return, similar to over-revving a racing car without its cooling system, leading to an inevitable breakdown.

Finding a drug that could activate rather than inhibit was challenging, given the pharmaceutical industry’s focus on inhibitors. However, Dos Santos Dias discovered a suitable drug that targets the protein PP2A, kick-starting the cancer cells into overactivity.

The perfect counterpart turned out to be a WEE1 inhibitor, a drug that attacks these overstimulated, stressed cells, preventing them from normal function.

This approach has shown promise in laboratory settings, with both cancer cells and mice carrying patient tumors responding positively to the treatment.

Importantly, the side effects appear to be manageable, raising hopes that normal cells can withstand the activation strategy better than cancer cells, which are already operating at full throttle.

One of the most compelling aspects of this research is its potential impact on treatment resistance, a significant hurdle in current cancer therapies where cells become non-responsive and often more aggressive.

Preliminary results suggest that cells resistant to this new treatment method might actually become less malignant, growing more slowly or not at all.

Internist-oncologist Neeltje Steeghs, who is involved in the clinical application of new treatments, highlights the uncertain path from laboratory to patient treatment but acknowledges the importance of moving promising research into clinical trials.

With plans to start patient trials by the end of the year, there is hope and curiosity about the effectiveness of this paradoxical treatment approach in a real-world setting.

The research community’s initial skepticism has evolved into substantial support, paving the way for further exploration of this unconventional method.

As this research progresses towards clinical trials, it challenges established norms and opens the door to potentially groundbreaking cancer treatments.

This work, currently awaiting publication in Cancer Discovery, marks a significant step in rethinking how we tackle one of the most formidable diseases facing humanity.

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The research findings can be found in bioRxiv.

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