Clin Cancer Res
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Abiraterone acetate is an orally administered potent inhibitor of cytochrome P450, family 17, subfamily A, polypeptide 1 (CYP17), which is essential for synthesis of testosterone from cholesterol. Although decreasing serum testosterone through inhibition of testicular function is the first line of treatment for men with metastatic prostate cancer, residual androgens may still be detected in patients treated with luteinizing hormone-releasing hormone agonists or antagonists. ⋯ Abiraterone's efficacy shows the importance of androgen signaling in patients with castrate-resistant metastatic disease, with additional confirmation from recent studies of other novel agents such as MDV3100, an androgen receptor signaling inhibitor. These promising results now pose a new angle to an old problem about hormonal therapy and raise new questions about how resistance develops, how to best sequence therapy, and how to optimize combinations with other emerging novel agents.
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SAR3419 is a novel anti-CD19 humanized monoclonal antibody conjugated to a maytansine derivate through a cleavable linker for the treatment of B-cell malignancies. SAR3419 combines the strengths of a high-potency tubulin inhibitor and the exquisite B-cell selectivity of an anti-CD19 antibody. The internalization and processing of SAR3419, following its binding at the surface of CD19-positive human lymphoma cell lines and xenograft models, release active metabolites that trigger cell-cycle arrest and apoptosis, leading to cell death and tumor regression. ⋯ Activity was reported in both schedules, in heavily pretreated patients of both follicular and diffuse large B-cell lymphoma subtypes, with a notable lack of significant hematological toxicity, validating SAR3419 as an effective antibody-drug conjugate and opening opportunities in the future. Numerous B-cell-specific anti-CD19 biologics are available to treat B-cell non-Hodgkin lymphoma, and early phase I results obtained with SAR3419 suggest that it is a promising candidate for further development in this disease. In addition, thanks to the broad expression of CD19, SAR3419 may provide treatment options for B-cell leukemias that are often CD20-negative.
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Tumor-associated immune responses have polarized effects in regulating tumor growth. Although a clear association has been shown between the tumor immune response and clinical outcome in colorectal and ovarian cancers, the role of immune markers for stratifying prognosis in non-small cell lung cancer (NSCLC) is less defined. ⋯ To identify prognostic immune genes, we reviewed all published gene-profiling studies in NSCLC and delineated the significance of immune genes by doing subanalysis on the microarray database of the NIH Director's Challenge study. This first comprehensive review of prognostic immune markers provides a foundation for further investigating immune responses in NSCLC.
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High-dose therapy (HDT) with autologous stem cell transplantation (ASCT) is the standard of care for eligible newly diagnosed multiple myeloma (MM) patients. Several randomized studies showed a survival advantage for patients undergoing transplantation, compared with conventional chemotherapy. Introduction of new drugs in this setting has markedly increased survival rates within the last 10 years. ⋯ Melphalan, prednisone, and thalidomide and bortezomib, melphalan, and prednisone are now the new standards of care for elderly patients. Preliminary results also support the role of the combination of melphalan, prednisone, and lenalidomide followed by maintenance therapy with lenalidomide in the treatment of elderly patients. Physicians now have a wider variety of treatment options to tailor the most appropriate and efficacious treatment according to their patients' characteristics.
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Pazopanib is an oral, multitargeted tyrosine kinase inhibitor that has been approved by the U. S. ⋯ Pazopanib thus joins sorafenib and sunitinib as one of the clinically available VEGF receptor (VEGFR)-targeted drugs for the treatment of patients with advanced clear cell renal cell cancer. The mechanism of action, preclinical and clinical data, and a comparison with the other drugs in its class are outlined below.