Скачать с ютуб Targeting Cancer Pathways: Tumor Resistance в хорошем качестве

Targeting Cancer Pathways: Tumor Resistance

Participating Experts: Michael Yaffe MD, PhD (MIT), Jeffrey Engleman MD, PhD (Harvard Medical School), and Michael Deininger MD, PhD (U. Utah) ⬇️ Expand “Show More” to view abstract and table of contents: ℹ️Download key signaling pathways in cancer: https://cst-science.com/5otvxd Recent advances in our understanding of cancer have revealed that the disease cannot be understood through simple analysis of genetic mutations within cancerous cells. Instead, tumors should be considered complex tissues in which the cancer cells evolve and communicate with the surrounding cellular microenvironment to promote their own survival and dissemination. Although therapies against specific signaling proteins or pathways have been remarkably successful at treating certain cancers, the tumors frequently develop resistance, leading to even more aggressive forms of the disease. This webinar focuses on how rewiring of signaling pathways in response to drug treatment contributes to resistance and how this knowledge can be leveraged to develop more effective treatment strategies. Topics covered include: • the specific molecules and pathways that are the targets for rationally designed therapies; • efforts to overcome resistance to the first FDA-approved therapy targeting a hyperactive kinase; • mechanisms by which tumor cells resist inhibitors that target cell survival and growth pathways; • how the rewiring of cell death pathways can sensitize cells to traditional chemotherapy agents. Table of Contents 0:00 Welcome and Introduction 2:44 Michael Yaffe speaker profile 3:39 Dynamic re-wiring of signaling networks as mechanisms for improving combination therapy for cancer 4:28 Signaling and systems biology - missing data that links genotype to phenotype 6:14 Static vs dynamic network rewiring 7:35 Combination drug screen for triple negative breast cancer 8:44 Efficacy of EGFR inhibition in BT-20 cells depends on timing of drug delivery 9:34 Subtype dependent responses to treatment 10:35 Understanding dynamic re-wiring – role of apoptosis 11:58 Working model 13:12 Nanoparticle development for time-staggered drug delivery in vivo 14:32 Combination erlotinib-doxorubicin nanoparticles in vivo 16:24 Generalizing time-staggered inhibition of RTK signaling for tumor sensitization 18:20 Conclusions 20:04 Jeffrey Engleman speaker profile 21:03 Resistance to tyrosine kinase inhibitors in lung cancer 21:41 Cancers with EGFR mutations are highly sensitive to EGFR kinase inhibitors 22:27 Cancers with ALK translocations are highly sensitive to ALK kinase inhibitors 26:03 Acquired resistance to targeted therapies 23:47 Sensitivity to tyrosine kinase inhibitors 28:48 One-third of crizotinib-resistant tumors harbor ALK resistance mutations 29:26 Spectrum of resistance mechanisms – results from repeat biopsy program 31:29 Serial biopsies reveal dynamic populations of different clones 33:15 Multiple populations in a single tumor nodule 36:07 Antitumor efficacy of ceritinib 36:51 Selection of new resistant clones on LDK378 (certinib) 37:57 Develop regimens: alternating and intermittent therapeutic combinations 39:44 Michael Deininger speaker profile 40:34 Protein kinases regulate key cell functions 41:22 Chronic myeloid leukemia (CML) 42:56 BCR-ABL kinase activity is central to CML pathogenesis 43:56 Imatinib improves survival in CML 44:40 BCR-ABL1 tyrosine kinase inhibitors (TKI) 47:03 Mechanisms of TKI resistance 48:20 Resistance mutations in BCR-ABL1 49:56 Preclinical characterization of Ponatinib 51:20 Accelerated mutagenesis screen: predicting mutation resistance to TKIs 53:49 Ponatinib Phase 2 study 55:47 T3151-inclusive compound mutations confer universal TKI resistance 58:48 Forcing BCR-ABL to commit mutational suicide 1:00:53 Auto-inhibition of ABL kinase activity 1:02:37 Inhibition of T315I in vitro with GNF-5 plus nilotinib 1:04:19 Questions and answers 👉 About CST®: Cell Signaling Technology (CST) is a private, family-owned company, founded by scientists and dedicated to providing high-quality research tools to the biomedical research community. Our employees operate worldwide from our U.S. headquarters in Massachusetts, and our offices in the Netherlands, China, and Japan. https://cellsignal.com/about All trademarks are the property of their respective owners. For the most up-to-date trademark information, please visit https://www.cellsignal.com/trademarks #Antibody #CSTWebinar