Targeting the EGFR and the PKB pathway in cancer.
The EGFR and PKB pathways are frequently activated in cancer, so are prime targets for cancer therapy. To this end, new inhibitors are being tested. EGFR inhibitors as single therapy have little benefit, although therapies that evoke an antitumor immune response are more effective. Resistance mutations within the EGFR are common, as is activation of the antiapoptotic PKB pathway via alternative tyrosine kinase receptors, especially other EGFR family members or IGF1R. To combat resistance, multitargeted EGFR inhibitors and combined inhibition of the EGFR and PKB are being investigated. Inhibition of the EGFR and PKB pathways also sensitizes cancer cells to chemotherapy. Thus, EGFR and PI3K/PKB inhibitors will be most effective when used in rational combinations of targeted inhibitors and traditional chemotherapy.
Klein
Shoshana
S
Unit of Cellular Signaling, Department of Biological Chemistry, The Hebrew University of Jerusalem, Givat Ram, Jerusalem, Israel. Kleins@cc.huji.ac.il
Levitzki
Alexander
A
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014411:Neoplastic Stem Cells / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000255:Adenosine Triphosphate; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D007527:Isoenzymes; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt