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Progress in cancer treatment that targets DNA repair mechanism



Researchers believe they have taken a step forward in harnessing a promising Ovarian cancer treatment option that, to date, has been limited by its toxicity and emerging drug resistance.

Ovarian cancer, often diagnosed at an advanced stage, presents significant treatment challenges because patients tend to develop resistance to conventional therapies quickly.

Despite aggressive treatment, recurrence rates remain high, and managing this disease effectively requires innovative approaches.

Poly-adenosine ribose polymerase (PARP) inhibitors have emerged as a treatment option, targeting specific DNA repair mechanisms in cancer cells. However, their use is often limited by toxicity and emerging drug resistance.

A new study led by researchers at Moffitt Cancer Center introduces an adaptive therapy approach that could optimise PARP inhibitor maintenance therapy, offering a more personalised and potentially less toxic treatment option for patients.

PARP inhibitors are a targeted therapy that block a protein that helps repair damaged DNA. This can keep cancer cells from repairing themselves once they’ve been damaged by chemotherapy, resulting in cancer cell death.

Despite their effectiveness, traditional dosing methods of administering the maximum tolerated dose often result in severe side effects and dose reductions, compromising treatment efficacy.

Moffitt researchers used mathematical modeling and in vitro experiments to compare adaptive dosing strategies.

They developed a model to test various adaptive schedules and found that dose modulation based on tumor response was superior to skipping doses.

“Adaptive therapy tailors treatment to the tumour’s dynamics, allowing us to adjust drug levels to match a patient’s specific disease characteristics,” said study author Alexander Anderson.

“Our findings suggest that modulation, rather than skipping doses, can halve the amount of drug used while maintaining its effectiveness. This approach reduces toxicity and can potentially delay the development of resistance.”

Researchers conducted time-lapse microscopy to observe ovarian cancer cell populations under different treatment schedules.

Their model revealed that continuous dose modulation effectively managed the tumor using significantly less medication than traditional methods.

In vivo experiments confirmed these results, demonstrating the practical viability of the adaptive approach. While the results are promising, the research continues to validate and refine adaptive therapy strategies.

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