Regulation of Ras signaling and function by plasma membrane microdomains
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- Goldfinger Lawrence E.
- Department of Anatomy & Cell Biology and The Sol Sherry Thrombosis Research Center, Lewis Katz School of Medicine at Temple University, and Cancer Biology Program, Fox Chase Cancer Center
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- Michael James V.
- Department of Medicine, Center for Translational Medicine, Thomas Jefferson University
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説明
<p>Together H-, N- and KRAS mutations are major contributors to ~30% of all human cancers. Thus, Ras inhibition remains an important anti-cancer strategy. The molecular mechanisms of isotypic Ras oncogenesis are still not completely understood. Monopharmacological therapeutics have not been successful in the clinic. These disappointing outcomes have led to attempts to target elements downstream of Ras, mainly targeting either the Phosphatidylinositol 3-Kinase (PI3K) or Mitogen-Activated Protein Kinase (MAPK) pathways. While several such approaches are moderately effective, recent efforts have focused on preclinical evaluation of combination therapies to improve efficacies. This review will detail current understanding of the contributions of plasma membrane microdomain targeting of Ras to mitogenic and tumorigenic signaling and tumor progression. Moreover, this review will outline novel approaches to target Ras in cancers, including targeting schemes for new drug development, as well as putative re-purposing of drugs in current use to take advantage of blunting Ras signaling by interfering with Ras plasma membrane microdomain targeting and retention.</p>
収録刊行物
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- BioScience Trends
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BioScience Trends 11 (1), 23-40, 2017
特定非営利活動法人 バイオ＆ソーシャル・サイエンス推進国際研究交流会
