The Raf/MEK/ERK pathway can govern drug resistance, apoptosis and sensitivity to targeted therapy

Roles of the Ras/Raf/MEK/ERK pathway in leukemia therapy

“…1,2 This pathway relays this information through interactions with various other proteins to the nucleus to control gene expression. [1][2][3][4][5][6][7][8][9][10][11][12] This review will discuss how these pathways may be aberrantly regulated in leukemia and contribute to therapeutic sensitivity/resistance and in some cases poor prognosis. [4][5]13 Inhibition of Ras (or Ras-related molecules), Raf, MEK and ERK may prove useful in leukemia treatment.…”

“…[1][2][3][4][5][6][7][8][9][10][11][12] Mutations can occur in the genes encoding pathway constituents (for example, Ras and Raf), upstream receptors (for example, Kit, Fms and Fms-like tyrosine kinase (Flt)-3) or chromosomal translocations (for example, BCR-ABL and TEL-platelet-derived growth factor receptor (PDGFR)), which activate this pathway. Chemotherapeutic drugs frequently used in leukemia therapy often activate this pathway.…”

Enhancing therapeutic efficacy by targeting non-oncogene addicted cells with combinations of signal transduction inhibitors and chemotherapy

“…Some of these signaling pathways are associated with chemotherapeutic drug resistance. 11,20,21,31,32,[37][38][39][40][41][42][43]58,59,67,68 Furthermore, the p53 tumor suppressor is a common target of many chemotherapeutic drugs and can interact with many signaling pathways. [69][70][71][72] Approaches that combine prolongation of wild-type p53 activity may enhance the effects of chemotherapeutic drugs, either in the presence of absence of signal transduction inhibitors.…”

“…While "non-oncogene" addicted cells were not as sensitive to signal transduction inhibitors as "oncogene-addicted" cells, 58,59 the "non-oncogene addicted" cells were sensitive to chemotherapeutic drugs and the therapeutic efficacy can be enhanced by targeted therapy. Therefore, it may be efficacious to target "non-oncogene addicted" pre-leukemia cells before the development of leukemic cells with combinations of chemotherapy and signal transduction inhibitors.…”

Resveratrol Affects Protein Kinase C Activity and Promotes Apoptosis in Human Colon Carcinoma Cells

“…The MAPK family has four members, including extracellular regulated kinases (ERKs), c-jun N-terminal or stress-activated protein kinases (JNK/SAPK), ERK 5/big MAP kinase 1 (BMK1) and the p38 group of protein kinases, which have been involved in distinct cellular processes. Activation of ERK has been considered to be involved in cell proliferation (McCubrey et al, 2007;Abrams et al, 2010); while inhibition of ERK activation with a MEK inhibitor, PD98059, induced apoptosis in a dose-dependent manner in breast cancer cells. The ERK pathway was up-regulated in human cancers, such as colon cancer (Davies et al, 2010), and blockage of the ERK pathway would enhance the induction of apoptosis in cancer cells .…”