Future oncology
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Vemurafenib was the first selective BRAF inhibitor licensed in cancer. It is indicated for the treatment of patients affected by advanced melanoma with BRAF V600 mutation. It has shown successful results in terms of efficacy together with a favorable toxicity profile. ⋯ Moreover, its efficacy and toxicity are compared with dabrafenib and ipilimumab. A number of trials with vemurafenib alone or in combination with other drugs are also analyzed. These trials will determine the role of vemurafenib in the treatment of BRAF mutant melanoma in forthcoming years.
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ABSTRACT Rearrangement of ALK gene has been identified as exerting a potent transforming effect as driver oncogene in patients with non-small-cell lung cancer (NSCLC). Crizotinib is a small-molecule oral inhibitor of ALK, c-Met/HGF receptor and ROS1 receptor kinases. ⋯ Resistance mechanisms such as secondary gatekeeper mutations in ALK gene and activation of other oncogenes have been identified to confer acquired resistance to crizotinib. This article reviews the pharmacological properties of crizotinib, preclinical and clinical results that led to its approval in ALK-positive NSCLC and current directions of clinical research in overcoming crizotinib resistance.
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Management of metastatic castration-resistant prostate cancer has changed markedly over the last decade with major shifts in the treatment paradigm, although ultimately still will progress despite currently available therapies. The sequencing or combination of these agents is an area of active investigation, since definitive prospective randomized trials to define the optimal choice of drug sequence have yet to be done or resulted. This article will highlight pivotal trials for currently approved therapies for metastatic castration-resistant prostate cancer and a suggestion for sequencing of these agents, as well as highlighting investigations using novel therapies for advanced prostate cancer.
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Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). ⋯ In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing.
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Obstructive sleep apnea (OSA) is a common disorder characterized by pauses in regular breathing. Apneic episodes lead to recurrent hypoxemia-reoxygenation cycles with concomitant cellular intermittent hypoxia. Studies suggest that intermittent hypoxia in OSA may influence tumorigenesis. ⋯ Current data relating OSA to risk of neoplastic disease remain scarce, but recent studies reveal the potential for a strong relation. More work is, therefore, needed on the impact of OSA on many cancer-related aspects. Results may offer enlightenment for improved cancer diagnosis and treatment.