PI3K/Akt signalling pathway specific inhibitors: a novel strategy to sensitize cancer cells to anti-cancer drugs.
The resistance of many types of cancer to chemotherapies represents the major hurdle in successful cancer treatment. Cancer cells can escape the toxic effect of most commonly used drugs despite their different chemical structure and intracellular targets. The mechanisms underlying the failure of chemotherapeutic drugs have been well studied. Here I review the role of a signalling pathway activated by the lipid kinase phosphoinositide 3-kinase (PI3K) and the serine/threonine kinase, protein kinase B (PKB) or Akt, in chemotherapeutic resistance. Activation of this pathway plays a key role in different cellular functions such as growth, migration survival and differentiation. Data accumulated in the last decade have established that this pathway plays a key role in cancer development and progression. More recently it has been shown that this pathway plays also a key role in resistance to chemotherapy. Therefore drugs designed to specifically target this pathway are under development to be used as single agent and in combination to chemotherapy to overcome therapeutic resistance.
Falasca
Marco
M
Queen Mary University of London, Barts and The London School of Medicine and Dentistry, Blizard Institute of Cell and Molecular Science, Centre for Diabetes, Inositide Signalling Group, London E1 2AT, UK. m.falasca@qmul.ac.uk
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome
D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt