Abstract
KRAS mutations are common in pancreatic and colorectal cancers and are associated with lack of response to anti-epidermal growth factor receptor therapy. Ras is an established therapeutic target that has long eluded efforts to develop specific inhibitors, while targeting downstream signaling pathways has proven largely ineffective, highlighting a need for rational combination strategies to overcome resistance. Recently, renewed interest in directly targeting Ras has led to the development of several small-molecule inhibitors that bind directly to K-Ras or its effector proteins, downregulation of K-Ras expression using therapeutic antisense oligonucleotides or siRNAs, and targeting scaffold proteins such as kinase suppressor of Ras. Indirect approaches to inhibiting K-Ras include combining inhibitors of the mitogen-activated protein kinase pathway with novel targeted agents. Immunotherapy in early studies has also shown clinical promise. This review summarizes the current evidence for each of these approaches.
Original language | English (US) |
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Pages (from-to) | 78-91 |
Number of pages | 14 |
Journal | Critical Reviews in Oncology/Hematology |
Volume | 130 |
DOIs | |
State | Published - Oct 2018 |
Keywords
- Colorectal cancer
- Gastrointestinal cancer
- K-Ras inhibitor
- Pancreatic cancer
ASJC Scopus subject areas
- Geriatrics and Gerontology
- Hematology
- Oncology