In model systems, bacteria present in human pancreatic tumors confer resistance to the anticancer drug gemcitabine. Debugging a cancer therapy Microbes contribute not only to the development of human diseases but also to the response of diseases to treatment. Geller et al. show that certain bacteria express enzymes capable of metabolizing the cancer chemotherapeutic drug gemcitabine into an inactive form. When bacteria were introduced into tumors growing in mice, the tumors became resistant to gemcitabine, an effect that was reversed by antibiotic treatment. Interestingly, a high percentage of human pancreatic ductal adenocarcinomas, a tumor type commonly treated with gemcitabine, contain the culprit bacteria. These correlative results raise the tantalizing possibility that the efficacy of an existing therapy for this lethal cancer might be improved by cotreatment with antibiotics. Science, this issue p. 1156 Growing evidence suggests that microbes can influence the efficacy of cancer therapies. By studying colon cancer models, we found that bacteria can metabolize the chemotherapeutic drug gemcitabine (2′,2′-difluorodeoxycytidine) into its inactive form, 2′,2′-difluorodeoxyuridine. Metabolism was dependent on the expression of a long isoform of the bacterial enzyme cytidine deaminase (CDDL), seen primarily in Gammaproteobacteria. In a colon cancer mouse model, gemcitabine resistance was induced by intratumor Gammaproteobacteria, dependent on bacterial CDDL expression, and abrogated by cotreatment with the antibiotic ciprofloxacin. Gemcitabine is commonly used to treat pancreatic ductal adenocarcinoma (PDAC), and we hypothesized that intratumor bacteria might contribute to drug resistance of these tumors. Consistent with this possibility, we found that of the 113 human PDACs that were tested, 86 (76%) were positive for bacteria, mainly Gammaproteobacteria.

中文翻译：

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肿瘤内细菌在介导肿瘤对化疗药物吉西他滨耐药中的潜在作用

在模型系统中，人类胰腺肿瘤中存在的细菌赋予抗癌药物吉西他滨抗性。调试癌症疗法 微生物不仅有助于人类疾病的发展，而且有助于疾病对治疗的反应。盖勒等人。表明某些细菌表达能够将癌症化疗药物吉西他滨代谢成无活性形式的酶。当细菌被引入小鼠体内生长的肿瘤中时，肿瘤对吉西他滨产生抗药性，抗生素治疗逆转了这种效果。有趣的是，高比例的人类胰腺导管腺癌（一种通常用吉西他滨治疗的肿瘤类型）含有罪魁祸首细菌。这些相关结果提出了一种诱人的可能性，即通过与抗生素共同治疗可能会提高现有疗法对这种致命癌症的疗效。科学，这个问题 p。1156 越来越多的证据表明，微生物可以影响癌症治疗的疗效。通过研究结肠癌模型，我们发现细菌可以将化疗药物吉西他滨（2',2'-二氟脱氧胞苷）代谢成其无活性形式，2',2'-二氟脱氧尿苷。代谢取决于细菌酶胞苷脱氨酶 (CDDL) 的长同种型的表达，主要见于 Gammaproteobacteria。在结肠癌小鼠模型中，吉西他滨耐药由瘤内γ-变形菌诱导，依赖于细菌 CDDL 的表达，并通过与抗生素环丙沙星共同治疗消除。吉西他滨常用于治疗胰腺导管腺癌 (PDAC)，我们假设瘤内细菌可能导致这些肿瘤的耐药性。与这种可能性一致，我们发现在测试的 113 个人类 PDAC 中，86 个（76%）对细菌呈阳性，主要是 Gammaproteobacteria。