Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR Cascade Inhibitors: How Mutations Can Result in Therapy Resistance and How to Overcome Resistance

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Stephen L. Abrams (Creator)

William H. Chappell (Creator)

Francesca Chiarini (Creator)

Lucio Cocco (Creator)

Camilla Evangelisti (Creator)

Richard A. Franklin (Creator)

Montalt Franklin (Creator)

Danijela Maksimovic-Ivanic (Creator)

Alberto M. Martelli (Creator)

James A. McCubrey (Creator)

Michele Milella (Creator)

Linda S. Steelman (Creator)

Agostino Tafuri (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: The Ras/Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR cascades are often activated by genetic alterations in upstream signaling molecules such as receptor tyrosine kinases (RTK). Integral components of these pathways, Ras, B-Raf, PI3K, and PTEN are also activated/inactivated by mutations. These pathways have profound effects on proliferative, apoptotic and differentiation pathways. Dysregulation of these pathways can contribute to chemotherapeutic drug resistance, proliferation of cancer initiating cells (CICs) and premature aging. This review will evaluate more recently described potential uses of MEK, PI3K, Akt and mTOR inhibitors in the proliferation of malignant cells, suppression of CICs, cellular senescence and prevention of aging. Ras/Raf/MEK/ERK and Ras/PI3K/PTEN/Akt/mTOR pathways play key roles in the regulation of normal and malignant cell growth. Inhibitors targeting these pathways have many potential uses from suppression of cancer, proliferative diseases as well as aging.

Additional Information

Publication

Other

Oncotarget; 3:10 p. 1068-1111

Language: English

Date: 2012

Keywords

Senescence, Drug Resistance, mTOR, Combination Therapy, PI3K, Aging, Raf, Targeted Therapy,, Cancer Stem Cells, Akt

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