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.
适应性疗法是一种受生态学启发的癌症治疗策略，其核心在于利用药物敏感与耐药亚克隆间的竞争关系，以控制肿瘤进展而非最大化杀伤癌细胞为目标，旨在克服耐药性并降低治疗毒性，从而优先保障患者生存期与生活质量。为开展临床试验做准备，本研究采用内分泌耐药的MCF7乳腺癌模型模拟二线治疗场景，在小鼠异种移植模型中测试了卡培他滨、吉西他滨单药及联合用药的适应性疗法方案。结果显示，单用卡培他滨的剂量调节适应性疗法虽较最大耐受剂量治疗延长了生存期（风险比=0.22，95%置信区间=0.043–1.1，p=0.065），但未达统计学显著性。然而，当采用双药交替策略时，无论是剂量调节疗法（风险比=0.11，95%置信区间=0.024–0.55，p=0.007）还是间歇性适应性疗法，均较联合高剂量治疗显著延长生存期（风险比=0.07，95%置信区间=0.013–0.42，p=0.003）。总体而言，单药（p<0.01）与联合用药（p<0.001）在降低剂量时均能延长生存期，且相较于高剂量治疗，适应性疗法组肿瘤呈现更少的增殖细胞（p=0.0026）与更多的凋亡细胞（p=0.045）。研究表明适应性疗法更适用于生长缓慢的肿瘤，且双药交替方案较联合用药展现出更好的应用前景。
肿瘤(癌症)患者之家