The phosphoinositide 3-kinase signalling pathway as a therapeutic target in squamous cell carcinoma of the head and neck.
Squamous cell carcinoma of the head and neck (SCCHN) is associated with high morbidity and mortality. Despite significant surgical advances and refinement in the delivery of chemotherapy and radiotherapy, prognosis has improved little in recent decades. Better local control has led to the late presentation of distant metastases and novel therapeutic agents are urgently required to prevent relapse, control disseminated disease and thus improve survival. PIK3CA encodes the p110alpha isoform of phosphoinositide 3-kinase (PI3-K) and is important in SCCHN, aberrations in its activity occurring early in the oncogenic process. PI3-K signalling promotes cell survival, proliferation, invasion and angiogenesis, all contributing to tumour progression. Activation of the PI3-K pathway may also mediate resistance to chemotherapy, radiotherapy and novel therapeutic agents such as epidermal growth factor receptor inhibitors. Elements of this signalling matrix, therefore, offer attractive therapeutic targets in SCCHN as inhibition of many malignant characteristics, as well as sensitisation to multiple treatment modalities, could be anticipated.
Rogers
Susanne J
SJ
Cancer Research UK Centre for Cancer Therapeutics, Tumour Biology and Metastasis Team, Institute of Cancer Research, McElwain Laboratories, Cotswold Rd, Belmont, Sutton, Surrey, SM2 5NG, UK.
Box
Carol
C
Harrington
Kevin J
KJ
Nutting
Chris
C
Rhys-Evans
Peter
P
Eccles
Suzanne A
SA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D015398:Signal Transduction / Q000187:drug effects*; D013379:Substrate Specificity
D000970:Antineoplastic Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors