Gastrointestinal stromal tumor molecular diagnostics in relation to the prediction of a therapeutic response to targeted biological therapy
Abstract
Targeted therapy based on the inhibition of the receptor tyrosine kinases has improved the outcome of patients with metastatic, recurrent and/or unresectable gastrointestinal stromal tumors (GIST). Activating mutations of KIT and PDGFRA genes, which code for receptor tyrosine kinases, play an important role in the malignant transformation of stromal cells in the gastrointestinal tract.
The response to targeted therapy is associated with the presence and type of mutations. Molecular identification of the primary mutational status became an important tool in predicting the response to therapy (sensibility/resistance).
The identification of secondary mutations occurring in patients treated with targeted therapy may explain the cause of acquired, secondary resistance of GIST. In these cases, mutational analysis represents a tool to explain failure of the therapy and provides a rationale for alternative therapeutic strategies.