[Potential combination of target therapy and radiation therapy in GI tract cancers].
At cellular level, signalization pathway activated by ErbB receptors participate to the proliferation, migration and differenciation of many cellular types. Observed alterations are mutations, overexpressions with or without gene amplification or abnormal stimulation by their ligands. The most frequently observed mutation is an extracellular deletion aiming to activate tyrosine kinase activity without ligand. Strategies to target the EGFr receptor include antisens oligonucleotids, antibodies directed to extracellular component of tyrosine kinase receptor. Only monoclonal antibodies and TKI have been developed in clinical research, mainly for oesophageal and rectal carcinomas. Solid tumor proliferation is under control of tumoral mechanisms and the interaction between tumor and microenvironment. In particular, angiogenesis is important during invasive and metastasis phases. The major role of Vasculoendothelial Growth Factor (VEGF) in angiogenesis is useful for tumor growth, which has been demonstrated by many convergent studies. Radiosensitivation or reversion of radioresistance could be obtained by inhibition of VEGF pathway. Antibodies directed against this molecule have been introduced in GI tract malignancies for the treatment of pancreatic and colic carcinomas.
Maingon
P
P
Département de Radiothérapie, Centre Georges-François-Leclerc, 1, rue du Professeur-Marion, Dijon Cedex, France. mcperrin@dijon.fnclcc.fr
Créhange
G
G
Peignaux
K
K
Truc
G
G
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D005770:Gastrointestinal Neoplasms / Q000628:therapy*; D006801:Humans; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant
D000970:Antineoplastic Agents; D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases