@article{bibcite_204266,
  keywords = {PI3Ki, breast cancer, cytochrome P450, diet and cancer treatment, gut-liver axis, microbiome metabolites, pancreatic cancer, pharmacokinetics, phytochemicals, soyasaponins},
  author = {Asael Roichman and Qianying Zuo and Sunghoon Hwang and Wenyun Lu and Ricardo Cordova and Michael MacArthur and Jacob Boyer and Sarah Mitchell and Jesse Powers and Sophia Koval and Craig Hunter and Jamie Rijmers and Rolf-Peter Ryseck and Jenna AbuSalim and Seema Chatterjee and Won Lee and Xincheng Xu and Xi Xing and Zihong Chen and Xianfeng Zeng and Siddharth Marwaha and Matthew McBride and Jessie Guo and Yibin Kang and Mohamed Donia and Joshua Rabinowitz},
  title = {Microbiome metabolism of dietary phytochemicals controls the anticancer activity of PI3K inhibitors.},
  abstract = {<p>Phosphatidylinositol 3-kinase (PI3K) signaling is both the effector pathway of insulin and among the most frequently activated pathways in human cancer. In murine cancer models, the efficacy of PI3K inhibitors is dramatically enhanced by a ketogenic diet, with a proposed mechanism involving dietary suppression of insulin. Here, we confirm profound diet-PI3K anticancer synergy but show that it is, surprisingly, unrelated to diet macronutrient composition. Instead, the diet-PI3K interaction involves microbiome metabolism of ingested phytochemicals. Specifically, murine ketogenic diet lacks the complex spectrum of phytochemicals found in standard chow, including the soy phytochemicals soyasaponins. We find that soyasaponins are converted by the microbiome into inducers of hepatic cytochrome P450 enzymes, and thereby lower PI3K inhibitor blood levels and anticancer activity. A high-carbohydrate, low-phytochemical diet synergizes with PI3K inhibition to treat cancer in mice, as do antibiotics that curtail the gut microbiome. Thus, diet impacts anticancer drug activity through phytochemical-microbiome-liver interactions.</p>},
  year = {2025},
  journal = {Cell},
  volume = {188},
  pages = {3065-3080.e21},
  month = {05/2025},
  issn = {1097-4172},
  doi = {10.1016/j.cell.2025.04.041},
  language = {eng},
}