The 3 R’s of cancer therapy: Response, Resistance, and Relapse
Jerry Radich, MD
Friday, December 7, 2018
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Chapters
Introduction
The 3 R’s: Response, Resistance, and Relapse
Simplistic View of Cancer: a Monolith
Patterns of response and resistance
Tumors Have Many Clones. Not One
4 identical mutations shared by one region of chest wall and perinephric metastasis
Darwinian Selection and Branched Evolution
Mutation Variant Clearance at Day 30
Initiating Mutations are Less Likely to be Cleared than Cooperating Mutations
Clonal progression in secondary AML
Cancer Often Has Many Clones
Functional Heterogeneity of Sub-Clones
Clonal structure hidden in bulk
Detection of multiple FLT3 mutations in AML
Complex Clonal Diversity in AML
Clonal structure hidden in bulk
Clone Distributions v. Null ho of Single Clone p< 2.4 e -142
Is Relapse a Mix of Sensitive & Resistant Clones?
Darwinian selection in CML
Darwin and cancer branched evolution
Summary
How to Accelerate Understanding of 3 R’s
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Conclusion
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