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Updated: Feb 10, 2026
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Using RNA-sequencing to Detect Novel Splice Variants Related to Drug Resistance in In Vitro Cancer Models
Published on: December 9, 2016
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A Convergence-Based Framework for Cancer Drug Resistance
David J Konieczkowski1, Cory M Johannessen2, Levi A Garraway3
1Harvard Radiation Oncology Program, Boston, MA 02114, USA.
Cancer Cell
|May 16, 2018
Summary
Drug resistance in cancer is complex but may stem from a few key convergence mechanisms. Understanding these pathways, like reactivation or bypass, can help develop new cancer therapies.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Therapeutics
Background:
- Drug resistance is a major challenge in cancer treatment, despite advances in targeted therapies and immunotherapy.
- Mechanisms of resistance are often multifactorial and complex, making them difficult to fully understand and address.
Purpose of the Study:
- To propose a parsimonious framework for understanding drug resistance in cancer.
- To identify common convergence mechanisms underlying targeted therapy and immunotherapy resistance.
Main Methods:
- Conceptual analysis of existing data on cancer drug resistance mechanisms.
- Identification of recurring patterns in how resistance develops across different cancer types and treatments.
Main Results:
- Identified three primary convergence mechanisms: pathway reactivation, pathway bypass, and pathway indifference.
- These convergences may explain resistance to both targeted therapies and immunotherapies.
- The framework suggests potential common strategies to overcome resistance.
Conclusions:
- A convergence-based framework simplifies the understanding of complex drug resistance.
- This model provides insights into resistance across diverse cancer types and therapeutic modalities.
- The identified convergences offer potential targets for novel therapeutic strategies to overcome resistance.
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