A phase I, dose-escalation study of the multitargeted receptor tyrosine kinase inhibitor, golvatinib, in patients with advanced solid tumors.

Purpose: Receptor tyrosine kinases c-Met and Ron transduce signals regulating cell migration and matrix invasion. This phase I dose-escalation trial tested golvatinib, a highly potent, small-molecule, ATP-competitive inhibitor of c-Met and multiple members of the Eph receptor family plus c-Kit and Ron.

Experimental Design: Patients with advanced solid tumors received golvatinib orally, once daily, continuously.

Optimization of circulating biomarkers of obatoclax-induced cell death in patients with small cell lung cancer.

Small cell lung cancer (SCLC) is an aggressive disease in which, after initial sensitivity to platinum/etoposide chemotherapy, patients frequently relapse with drug-resistant disease. Deregulation of the Bcl-2 pathway is implicated in the pathogenesis of SCLC, and early phase studies of Bcl-2 inhibitors have been initiated in SCLC. Obatoclax is a small-molecule drug designed to target the antiapoptotic Bcl-2 family members to a proapoptotic effect.

X-linked inhibitor of apoptosis protein as a therapeutic target.

Dysregulation of apoptosis has been shown to contribute to many diseases, including cancer formation, development and resistance, as well as neurodegenerative and autoimmune disorders. One mechanism through which tumour cells are believed to acquire resistance to apoptosis is by overexpression of X-linked inhibitor of apoptosis protein (XIAP), which belongs to a family of inhibitor of apoptosis proteins. When XIAP is overexpressed, cancer cells are rendered resistant to apoptosis, both intrinsically and in response to chemotherapy and radiotherapy.

Novel therapeutic targets in lung cancer: Inhibitor of apoptosis proteins from laboratory to clinic.

Lung cancer is the leading cause of cancer death worldwide. Despite the introduction of new agents and schedules, chemotherapy still obtains unsatisfactory overall response rates, rare complete remissions and responses of relatively short duration. The inhibitor of apoptosis proteins (IAPS) are a family of caspase inhibitors that selectively bind and inhibit caspases-3, -7, and -9.

Second-line treatment of postmenopausal women with advanced breast carcinoma.

Breast cancer is the most prevalent cancer in women and, currently, there is no standard of care for the treatment of metastatic disease. Treatment options are based on a number of tumor- and patient-related factors. This review explores some of these options, including the use of hormonal manipulation in the treatment of hormone-positive disease, current chemotherapy options and the use of targeted therapies, such as trastuzumab.