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• W3080327101 abstract "Abstract Durable control of invasive solid tumors necessitates identifying therapeutic resistance mechanisms and effective drug combinations. A promising approach to tackle the cancer drug resistance problem is to build mechanistic mathematical models of the signaling network of cancer cells, and explicitly model the dynamics of information flow through this network under distinct genetic conditions and in response to perturbations. In this work, we used a network-based mathematical model to identify sensitivity factors and drug combinations for the PI3Kα inhibitor alpelisib, which was recently approved for ER+ PIK3CA mutant breast cancer. We experimentally validated the model-predicted efficacious combination of alpelisib and BH3 mimetics (e.g. MCL1 inhibitors) in ER+ breast cancer cell lines. We also experimentally validated the reduced sensitivity to alpelisib caused by FOXO3 knockdown, which is a novel potential resistance mechanism. Our experimental results showed cell line-specific sensitivity to the combination of alpelisib and BH3 mimetics, which was driven by the choice of BH3 mimetics. We find that cell lines were sensitive to the addition of either MCL1 inhibitor s63845 alone or in combination with BCL-XL/BCL-2 inhibitor navitoclax, and that the need for the combination of both BH3 mimetics was predicted by the expression of BCL-XL. Based on these results, we developed cell line-specific network models that are able to recapitulate the observed differential response to alpelisib and BH3 mimetics, and also incorporate the most recent knowledge on resistance and response to PI3Kα inhibitors. Overall, we present an approach for the development, experimental testing, and refining of mathematical models, which we apply to the context of PI3Kα inhibitor drug resistance in breast cancer. Our approach predicted and validated PI3Kα inhibitor sensitivity factors (FOXO3 knockdown) and drug combinations (BH3 mimetics), and illustrates that network-based mathematical models can contribute to overcoming the challenge of cancer drug resistance." @default.
• W3080327101 created "2020-09-01" @default.
• W3080327101 creator A5001090073 @default.
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• W3080327101 creator A5020013190 @default.
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• W3080327101 creator A5042886213 @default.
• W3080327101 creator A5055952938 @default.
• W3080327101 creator A5067967688 @default.
• W3080327101 creator A5068721624 @default.
• W3080327101 date "2020-08-25" @default.
• W3080327101 modified "2023-10-07" @default.
• W3080327101 title "Cell line-specific network models of ER+ breast cancer identify PI3Kα inhibitor sensitivity factors and drug combinations" @default.
• W3080327101 cites W1509669696 @default.
• W3080327101 cites W1966828006 @default.
• W3080327101 cites W1968852924 @default.
• W3080327101 cites W1975570973 @default.
• W3080327101 cites W1981517713 @default.
• W3080327101 cites W1981898075 @default.
• W3080327101 cites W1996413533 @default.
• W3080327101 cites W1996695017 @default.
• W3080327101 cites W2002226709 @default.
• W3080327101 cites W2004280628 @default.
• W3080327101 cites W2017187984 @default.
• W3080327101 cites W2017540124 @default.
• W3080327101 cites W2037720820 @default.
• W3080327101 cites W2057366353 @default.
• W3080327101 cites W2071463092 @default.
• W3080327101 cites W2080534618 @default.
• W3080327101 cites W2093917816 @default.
• W3080327101 cites W2102004296 @default.
• W3080327101 cites W2103732635 @default.
• W3080327101 cites W2104036704 @default.
• W3080327101 cites W2108541764 @default.
• W3080327101 cites W2118217667 @default.
• W3080327101 cites W2119874496 @default.
• W3080327101 cites W2121619780 @default.
• W3080327101 cites W2122624068 @default.
• W3080327101 cites W2122902176 @default.
• W3080327101 cites W2137035181 @default.
• W3080327101 cites W2153096480 @default.
• W3080327101 cites W2155228605 @default.
• W3080327101 cites W2156563694 @default.
• W3080327101 cites W2156918228 @default.
• W3080327101 cites W2157633567 @default.
• W3080327101 cites W2165056381 @default.
• W3080327101 cites W2166525118 @default.
• W3080327101 cites W2197234859 @default.
• W3080327101 cites W2214074259 @default.
• W3080327101 cites W2302083974 @default.
• W3080327101 cites W2309969893 @default.
• W3080327101 cites W2506550081 @default.
• W3080327101 cites W2509236360 @default.
• W3080327101 cites W2534349779 @default.
• W3080327101 cites W2601176113 @default.
• W3080327101 cites W2616761213 @default.
• W3080327101 cites W2620174055 @default.
• W3080327101 cites W2735132087 @default.
• W3080327101 cites W2757097548 @default.
• W3080327101 cites W2790669965 @default.
• W3080327101 cites W2795073885 @default.
• W3080327101 cites W2802173235 @default.
• W3080327101 cites W2809999132 @default.
• W3080327101 cites W2811244167 @default.
• W3080327101 cites W2891700678 @default.
• W3080327101 cites W2902000707 @default.
• W3080327101 cites W2902257786 @default.
• W3080327101 cites W2903143832 @default.
• W3080327101 cites W2903599006 @default.
• W3080327101 cites W2905887518 @default.
• W3080327101 cites W2912993657 @default.
• W3080327101 cites W2917986762 @default.
• W3080327101 cites W2938305903 @default.
• W3080327101 cites W2944727022 @default.
• W3080327101 cites W2945564879 @default.
• W3080327101 cites W2950427358 @default.
• W3080327101 cites W2951789849 @default.
• W3080327101 cites W2952121859 @default.
• W3080327101 cites W2955759669 @default.
• W3080327101 cites W2961945259 @default.
• W3080327101 cites W2963655326 @default.
• W3080327101 cites W2966546269 @default.
• W3080327101 cites W2967392952 @default.
• W3080327101 cites W2980008739 @default.
• W3080327101 cites W2988773550 @default.
• W3080327101 cites W3001475835 @default.
• W3080327101 cites W3005073090 @default.
• W3080327101 cites W3012647537 @default.
• W3080327101 cites W3015152600 @default.
• W3080327101 cites W3019012186 @default.
• W3080327101 cites W3024684302 @default.
• W3080327101 cites W3034207086 @default.
• W3080327101 cites W3045659462 @default.
• W3080327101 cites W4211214747 @default.
• W3080327101 cites W2085114365 @default.
• W3080327101 doi "https://doi.org/10.1101/2020.08.25.261370" @default.

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