부산대학교 도서관

Simple Summary: The biggest obstacle to curing cancer is the fact that cancers often harbor mutant cells, called resistant cells, that are unaffected by cancer drugs. We tested a strategy for maintaining control over resistant cells called adaptive therapy. We tested this strategy on mice that had human breast cancer. In adaptive therapy, we aim to keep alive many cancer cells that are sensitive to cancer drugs and use them to compete with the resistant cells. We can prevent the sensitive cells from growing out of control using occasional low doses of a cancer drug. Competition with the sensitive cells prevents the resistant cells from growing out of control, resulting in long-term control of the cancer. Thus, we turn cancer into a chronic, nonlethal disease. Our experiment showed the effectiveness of this approach and how we might make it even better by switching between two drugs. Adaptive therapy, an ecologically inspired approach to cancer treatment, aims to overcome resistance and reduce toxicity by leveraging competitive interactions between drug-sensitive and drug-resistant subclones, prioritizing patient survival and quality of life instead of killing the maximum number of cancer cells. In preparation for a clinical trial, we used endocrine-resistant MCF7 breast cancer to stimulate second-line therapy and tested adaptive therapy using capecitabine, gemcitabine, or their combination in a mouse xenograft model. Dose modulation adaptive therapy with capecitabine alone increased survival time relative to MTD but not statistically significantly (HR = 0.22, 95% CI = 0.043–1.1, p = 0.065). However, when we alternated the drugs in both dose modulation (HR = 0.11, 95% CI = 0.024–0.55, p = 0.007) and intermittent adaptive therapies, the survival time was significantly increased compared to high-dose combination therapy (HR = 0.07, 95% CI = 0.013–0.42, p = 0.003). Overall, the survival time increased with reduced dose for both single drugs (p < 0.01) and combined drugs (p < 0.001), resulting in tumors with fewer proliferation cells (p = 0.0026) and more apoptotic cells (p = 0.045) compared to high-dose therapy. Adaptive therapy favors slower-growing tumors and shows promise in two-drug alternating regimens instead of being combined. [ABSTRACT FROM AUTHOR]