Gastrointestinal stromal tumors (GISTs): from science to targeted therapy.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. GISTs represent a distinct category of tumors characterized by oncogenic mutations of the KIT receptor tyrosine kinase in a majority of patients. KIT is useful not only for the diagnosis but also for targeted therapy of this disease. Imatinib, a tyrosine kinase inhibitor, is widely used in advanced and metastatic GISTs. This agent revolutionized the treatment strategy of advanced disease and is being tested in the neoadjuvant and adjuvant settings with encouraging results. New therapeutic agents like sunitinib have now been approved, enriching the treatment scenario for imatinib-resistant GISTs. The present review reports on the peculiar characteristics of this disease through its biology and molecular patterns, focusing on the predictive value of KIT mutations and their correlation with clinical outcome as well as on the activity of and resistance to approved targeted drugs.

Clinical usefulness of bisphosphonates in oncology: treatment of bone metastases, antitumoral activity and effect on bone resorption markers.

The present article overviews the role of bisphosphonates for the treatment and prevention of bone metastases and their antiangiogenic effects and antitumoral activity. The skeleton is a frequent and clinically relevant site of metastasis in cancer patients. The major events related to bone metastases include bone pain, bone loss, hypercalcemia, spinal cord compression, and fractures. On the basis of their radiographic features, bone metastases are classified as osteoblastic, osteoclastic, or mixed. The primary goals of treatment of bone metastases are reduction of the risk of pathological fractures and other skeletal-related events, and pain control. Bisphosphonates are used to prevent pathological fractures by inhibition of osteoclasts. Recent studies suggest that bisphosphonates have some direct antitumoral activity, mainly mediated through the blockade of angiogenic pathways. Further clinical studies are needed to determine the optimal treatment duration, timing and schedule of bisphosphonates, assess their role as adjuvant therapy for the prevention of bone metastases, and establish their antiangiogenic activity in association with standard cytotoxic and hormonal drugs for treatment of patients with advanced disease.

Clinical benefit of intermittent administration of imatinib in a patient with metastatic gastrointestinal stromal tumour.

Gastrointestinal stromal tumours (GISTs) are mesenchymal tumours of the gastrointestinal tract, resistant to conventional chemotherapy and radiotherapy, but responsive to imatinib. Acquired resistance to imatinib has been reported in some patients, and several studies have suggested the possibility of overcoming imatinib resistance by increasing the dose of the drug. This case shows the possibility of obtaining clinical benefit with intermittent administration of imatinib in a patient who developed acquired resistance to a high dose of the drug.