Tyrosine kinase inhibitor therapies for gastrointestinal stromal tumours

Novel receptor tyrosine kinase targeted combination therapies for imatinib-resistant gastrointestinal stromal tumors (GIST)

BACKGROUND c-Kit/α-PDGFR targeted therapies are effective for gastrointestinal stromal tumors (GIST), but, >50% develop drug resistance. METHODS RTK expression (c-Kit, c-Met, AXL, HER-1, HER-2, IGF-1R) in pre-/post-imatinib (IM) GIST patient samples (n=16) and 4 GIST cell lines were examined for RTK inhibitor activity. GIST-882 cells were cultured in IM every other day, cells collected (1 wee...

Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review).

Treatment of patients affected by advanced or inoperable GIST was revolutionized by the use of the tyrosine kinase inhibitors. Despite the fact that most patients have a good durable response of disease, they develop a resistance to treatments after a median time of 24 months. The acquired resistance is an emerging aspect in medical oncology especially in the era of target therapies. The aim of...

Tyrosine kinase inhibition in renal cell carcinoma and gastrointestinal stromal tumours: case reports.

BACKGROUND Sunitinib malate is approved multinationally for the treatment of metastatic renal cell carcinoma (mRCC) and advanced imatinib-refractory gastrointestinal stromal tumour (GIST). Greater exposure to sunitinib is associated with improved efficacy. Therefore, minimising the impact of adverse events (AEs) on patient quality of life is important to enable patients to achieve optimal expos...

Gastrointestinal stromal tumours (GIST)

Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor.

INTRODUCTION Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the intestinal tract. Nearly all tumors have an activating mutation in the KIT or, less often, PDGFRalpha, gene. Therapy with tyrosine kinase inhibitors benefits over 80% of patients with advanced GIST, but most patients eventually develop drug resistance. METHODS Forty patients with metastatic GIST were treated ...