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Characterize Disease-related Mutants of RAF Family Kinases by Using a Set of Practical and Feasible Methods
Published on: July 17, 2019
Therapeutic resistance resulting from mutations in Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR signaling pathways
James A McCubrey1, Linda S Steelman, C Ruth Kempf
1Department of Microbiology and Immunology, Brody School of Medicine at East Carolina University, Greenville, North Carolina 27858, USA. mccubreyj@ecu.edu
Journal of Cellular Physiology
|February 9, 2011
Summary
Drug resistance in cancer therapy is a major challenge. This review highlights how dysregulated cell growth pathways, like Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR, contribute to chemotherapy and targeted therapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Chemotherapy is a cornerstone of cancer treatment but often faces challenges with drug resistance.
- Targeted therapies offer promise but also encounter resistance mechanisms.
- Signaling pathways regulating cell growth are frequently implicated in therapeutic resistance.
Purpose of the Study:
- To review the role of key cell growth signaling pathways in cancer drug resistance.
- To examine how dysregulation of Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways contributes to resistance.
- To focus on PTEN regulation as a critical factor in therapy resistance.
Main Methods:
- Literature review of studies on cancer drug resistance mechanisms.
- Analysis of signaling pathways involved in cell growth and their relation to therapy resistance.
- Detailed examination of PTEN gene regulation and its impact on treatment outcomes.
Main Results:
- Aberrant signaling in Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways is linked to resistance against chemotherapy and targeted therapies.
- Genetic alterations in these pathways and upstream receptors contribute to their dysregulation.
- PTEN, a tumor suppressor, is frequently dysregulated in cancer, promoting therapy resistance.
Conclusions:
- Controlling dysregulated cell growth signaling pathways is crucial for overcoming cancer therapy resistance.
- Targeting PTEN regulation may offer a strategy to improve treatment efficacy.
- Further research into these pathways can lead to improved cancer therapies and patient outcomes.
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