Black, J. R. M. & McGranahan, N. Genetic and non-genetic clonal diversity in cancer evolution. Nat. Rev. Cancer 21, 379392 (2021).
Article CAS PubMed Google Scholar
Dagogo-Jack, I. & Shaw, A. T. Tumour heterogeneity and resistance to cancer therapies. Nat. Rev. Clin. Oncol. 15, 8194 (2018).
Article CAS PubMed Google Scholar
Junttila, M. R. & de Sauvage, F. J. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature 501, 346354 (2013).
Article CAS PubMed Google Scholar
Topalian, S. L., Taube, J. M., Anders, R. A. & Pardoll, D. M. Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy. Nat. Rev. Cancer 16, 275287 (2016).
Article CAS PubMed PubMed Central Google Scholar
Purim, O. et al. Biomarker-driven therapy in metastatic gastric and esophageal cancer: Real-life clinical experience. Target Oncol. 13, 217226 (2018).
Article PubMed PubMed Central Google Scholar
Sveen, A., Kopetz, S. & Lothe, R. A. Biomarker-guided therapy for colorectal cancer: Strength in complexity. Nat. Rev. Clin. Oncol. 17, 1132 (2020).
Article PubMed Google Scholar
Hanahan, D. & Weinberg, R. A. Hallmarks of cancer: The next generation. Cell 144, 646674 (2011).
Article CAS PubMed Google Scholar
Celi-Terrassa, T. & Kang, Y. Distinctive properties of metastasis-initiating cells. Genes Dev. 30, 892908 (2016).
Article PubMed PubMed Central Google Scholar
Roos, W. P., Thomas, A. D. & Kaina, B. DNA damage and the balance between survival and death in cancer biology. Nat. Rev. Cancer 16, 2033 (2016).
Article CAS PubMed Google Scholar
Brown, J. S., O'Carrigan, B., Jackson, S. P. & Yap, T. A. Targeting DNA repair in cancer: Beyond PARP Inhibitors. Cancer Discov. 7, 2037 (2017).
Article CAS PubMed Google Scholar
Pili, P. G., Tang, C., Mills, G. B. & Yap, T. A. State-of-the-art strategies for targeting the DNA damage response in cancer. Nat. Rev. Clin. Oncol. 16, 81104 (2019).
Article PubMed PubMed Central Google Scholar
Cleary, J. M., Aguirre, A. J., Shapiro, G. I. & DAndrea, A. D. Biomarker-guided development of DNA repair inhibitors. Mol. Cell 78, 10701085 (2020).
Article CAS PubMed PubMed Central Google Scholar
Palmer, A. C., Chidley, C. & Sorger, P. K. A curative combination cancer therapy achieves high fractional cell killing through low cross-resistance and drug additivity. Elife 8, e50036 (2019).
Article PubMed PubMed Central Google Scholar
Palmer, A. C. & Sorger, P. K. Combination cancer therapy can confer benefit via patient-to-patient variability without drug additivity or synergy. Cell 171, 16781691.e13 (2017).
Article CAS PubMed PubMed Central Google Scholar
Dry, J. R., Yang, M. & Saez-Rodriguez, J. Looking beyond the cancer cell for effective drug combinations. Genome Med 8, 125 (2016).
Article PubMed PubMed Central Google Scholar
Al-Lazikani, B., Banerji, U. & Workman, P. Combinatorial drug therapy for cancer in the post-genomic era. Nat. Biotechnol. 30, 679692 (2012).
Article CAS PubMed Google Scholar
Menden, M. P. et al. Community assessment to advance computational prediction of cancer drug combinations in a pharmacogenomic screen. Nat. Commun. 10, 2674 (2019).
Article PubMed PubMed Central Google Scholar
Paller, C. J. et al. Factors affecting combination trial success (FACTS): Investigator survey results on early-phase combination trials. Front. Med. (Lausanne) 6, 122 (2019).
Article PubMed Google Scholar
Huang, L. et al. Driver network as a biomarker: systematic integration and network modeling of multi-omics data to derive driver signaling pathways for drug combination prediction. Bioinformatics 35, 37093717 (2019).
Article CAS PubMed PubMed Central Google Scholar
Celebi, R., Bear Dont Walk, O., Movva, R., Alpsoy, S. & Dumontier, M. In-silico prediction of synergistic anti-cancer drug combinations using multi-omics data. Sci. Rep. 9, 8949 (2019).
Article PubMed PubMed Central Google Scholar
Preuer, K. et al. DeepSynergy: Predicting anti-cancer drug synergy with deep learning. Bioinformatics 34, 15381546 (2018).
Article CAS PubMed Google Scholar
Bulusu, K. C. et al. Modelling of compound combination effects and applications to efficacy and toxicity: state-of-the-art, challenges and perspectives. Drug Discov. Today 21, 225238 (2016).
Article CAS PubMed Google Scholar
Yuan, B. et al. CellBox: Interpretable machine learning for perturbation biology with application to the design of cancer combination therapy. Cell Syst. 12, 128140.e4 (2021).
Article CAS PubMed Google Scholar
Zou, J. et al. Neighbor communities in drug combination networks characterize synergistic effect. Mol. Biosyst. 8, 3185 (2012).
Article CAS PubMed Google Scholar
Kholodenko, B. N. et al. Untangling the wires: a strategy to trace functional interactions in signaling and gene networks. Proc. Natl. Acad. Sci. USA 99, 1284112846 (2002).
Article CAS PubMed PubMed Central Google Scholar
Kholodenko, B. N., Rauch, N., Kolch, W. & Rukhlenko, O. S. A systematic analysis of signaling reactivation and drug resistance. Cell Rep. 35, 109157 (2021).
Article CAS PubMed PubMed Central Google Scholar
Rukhlenko, O. S. et al. Dissecting RAF inhibitor resistance by structure-based modeling reveals ways to overcome oncogenic RAS Signaling. Cell Syst. 7, 161179.e14 (2018).
Article CAS PubMed PubMed Central Google Scholar
Erdem, C. et al. A scalable, open-source implementation of a large-scale mechanistic model for single cell proliferation and death signaling. Nat. Commun. 13, 3555 (2022).
Article CAS PubMed PubMed Central Google Scholar
Frhlich, F. et al. Efficient parameter estimation enables the prediction of drug response using a mechanistic pan-cancer pathway model. Cell Syst. 7, 567579.e6 (2018).
Article PubMed Google Scholar
Szalay, K. Z. & Csermely, P. Computer implemented method, processor device and computer program product for designing intervention into real complex systems (2020).
Bliss, C. I. The toxicity of poisons applied jointly 1. Ann. Appl. Biol. 26, 585615 (1939).
Article CAS Google Scholar
Kim, H. et al. Targeting the ATR/CHK1 axis with PARP inhibition results in tumor regression in BRCA-mutant ovarian cancer models. Clin. Cancer Res 23, 30973108 (2017).
Article CAS PubMed Google Scholar
Hinton, G. E. Connectionist learning procedures. Artif. Intell. 40, 185234 (1989).
Article Google Scholar
Hastie, T., Tibshirani, R. & Friedman, J. Linear methods for regression. in 4399 (2009). https://doi.org/10.1007/978-0-387-84858-7_3.
Ke, G. et al. LightGBM: A highly efficient gradient boosting decision tree. In Advances in Neural Information Processing Systems 30, 31483156 (Curran Associates, Inc., 2017).
Chen, D., Liu, X., Yang, Y., Yang, H. & Lu, P. Systematic synergy modeling: Understanding drug synergy from a systems biology perspective. BMC Syst. Biol. 9, 56 (2015).
Article PubMed PubMed Central Google Scholar
Chen, D., Zhang, H., Lu, P., Liu, X. & Cao, H. Synergy evaluation by a pathway-pathway interaction network: A new way to predict drug combination. Mol. Biosyst. 12, 614623 (2016).
Article CAS PubMed Google Scholar
Parker, J. L. et al. Does biomarker use in oncology improve clinical trial failure risk? A large-scale analysis. Cancer Med. 10, 19551963 (2021).
Article CAS PubMed PubMed Central Google Scholar
Riches, L. C. et al. Pharmacology of the ATM inhibitor AZD0156: Potentiation of irradiation and olaparib responses preclinically. Mol. Cancer Ther. 19, 1325 (2020).
Article CAS PubMed Google Scholar
Mak, J. P. Y., Ma, H. T. & Poon, R. Y. C. Synergism between ATM and PARP1 inhibition involves DNA damage and abrogating the G 2 DNA damage checkpoint. Mol. Cancer Ther. 19, 123134 (2020).
Article CAS PubMed Google Scholar
Lloyd, R. L. et al. Combined PARP and ATR inhibition potentiates genome instability and cell death in ATM-deficient cancer cells. Oncogene 39, 48694883 (2020).
Article CAS PubMed PubMed Central Google Scholar
Kim, K. A. et al. Systematic calibration of a cell signaling network model. BMC Bioinforma. 11, 202 (2010).
Article Google Scholar
Kamel, D., Gray, C., Walia, J. S. & Kumar, V. PARP inhibitor drugs in the treatment of breast, ovarian, prostate and pancreatic cancers: An update of clinical trials. Curr Drug Targets 19, (2018).
Zhu, H. et al. PARP inhibitors in pancreatic cancer: molecular mechanisms and clinical applications. Mol. Cancer 19, 49 (2020).
Article CAS PubMed PubMed Central Google Scholar
Mirza, M. R. et al. The forefront of ovarian cancer therapy: Update on PARP inhibitors. Ann. Oncol. 31, 11481159 (2020).
Article CAS PubMed Google Scholar
Noordermeer, S. M. & van Attikum, H. PARP inhibitor resistance: A tug-of-war in BRCA-mutated cells. Trends Cell Biol. 29, 820834 (2019).
Article CAS PubMed Google Scholar
Criscuolo, D., Morra, F., Giannella, R., Cerrato, A. & Celetti, A. Identification of novel biomarkers of homologous recombination defect in DNA repair to predict sensitivity of prostate cancer cells to PARP-inhibitors. Int. J. Mol. Sci. 20, 3100 (2019).
Article CAS PubMed PubMed Central Google Scholar
Polzien, L. et al. Identification of novel in vivo phosphorylation sites of the human proapoptotic protein BAD: pore-forming activity of BAD is regulated by phosphorylation. J. Biol. Chem. 284, 2800428020 (2009).
Article CAS PubMed PubMed Central Google Scholar
Avvakumov, N. et al. Conserved molecular interactions within the HBO1 acetyltransferase complexes regulate cell proliferation. Mol. Cell Biol. 32, 689703 (2012).
Article CAS PubMed PubMed Central Google Scholar
Hanigan, C. L. et al. An inactivating mutation in HDAC2 leads to dysregulation of apoptosis mediated by APAF1. Gastroenterology 135, 16541664.e2 (2008).
Article CAS PubMed Google Scholar
Park, J.-M. & Kang, T.-H. Transcriptional and posttranslational regulation of nucleotide excision repair: The guardian of the genome against ultraviolet radiation. Int. J. Mol. Sci. 17, 1840 (2016).
Article PubMed PubMed Central Google Scholar
Marteijn, J. A., Lans, H., Vermeulen, W. & Hoeijmakers, J. H. J. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 15, 465481 (2014).
Article CAS PubMed Google Scholar
Here is the original post: