Testing Adaptive Therapy Protocols Using Gemcitabine and Capecitabine in a Preclinical Model of Endocrine-Resistant Breast Cancer.
Testing Adaptive Therapy Protocols Using Gemcitabine and Capecitabine in a Preclinical Model of Endocrine-Resistant Breast Cancer.
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DOI：
10.3390/cancers16020257
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发表时间：
2024-01-06
期刊：
影响因子：
5.2
通讯作者：
Maley, Carlo C.
中科院分区：
文献类型：
--
作者：
Seyedi, Sareh;Teo, Ruthanne;Foster, Luke;Saha, Daniel;Mina, Lida;Northfelt, Donald;Anderson, Karen S.;Shibata, Darryl;Gatenby, Robert;Cisneros, Luis H.;Troan, Brigid;Anderson, Alexander R. A.;Maley, Carlo C.
关键词：
治愈癌症的最大障碍是，癌细胞经常被称为抗药性细胞，而我们的抗药性细胞不受欢迎。从偶尔的癌症药物中，与敏感细胞的竞争变得失控。
自适应治疗是一种受生态启发的癌症治疗方法，旨在通过利用对药物敏感和耐药的亚克隆的竞争性相互作用来降低毒性，并优先使用患者的生存和生活质量，而不是杀死癌症的最大癌症，我们使用了临床疗法，并使用了临床疗法，我们使用了乳腺癌的疗法。 ，，，，它们在小鼠异种移植模型中的组合与单独的剂量调节疗法相对于MTD增加了生存时间，但在统计学上没有显着（HR = 0.22，95％CI = 0.043–1.1，p = 0.065）自适应疗法，生存时间显着增加与高剂量的组合治疗（HR = 0.07，95％CI = 0.013-0.42，P = 0.003）治疗有利于生长缓慢的肿瘤，并在两种药物改变方案而不是合并。
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.
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影响因子：
17.1
作者：
Enriquez-Navas PM;Kam Y;Das T;Hassan S;Silva A;Foroutan P;Ruiz E;Martinez G;Minton S;Gillies RJ;Gatenby RA
通讯作者：
Gatenby RA
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
5.2
作者：
Kurata, Nobuaki;Fujta, Hayato;Tanaka, Masao
通讯作者：
Tanaka, Masao
影响因子：
7.3
作者：
Duan, WR;Garner, DS;Blomme, EAG
通讯作者：
Blomme, EAG
影响因子：
5.4
作者：
Gatenby, Robert A.;Brown, Joel S.
通讯作者：
Brown, Joel S.