The Mount Sinai journal of medicine, New York
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The myeloproliferative neoplasms represent a diverse group of hematologic malignancies that have been the subject of intense investigation over the last decade. Although clinical trials of the much anticipated small molecule inhibitors of Janus kinase 2 have shown that these experimental agents are successful in palliating many of the symptoms associated with the myeloproliferative neoplasms, they have not been reported to affect the disease initiating hematopoietic stem cell population or to alter the natural history of these disorders. Investigators remain optimistic that new information about the genetic and cellular origins gained from the efforts of numerous laboratories will ultimately translate in to the identification of new drug targets and more effective therapies. We hypothesize that ultimately, the use of combinations of drugs including chromatin modifying agents, immunomodulatory agents, anti-apoptotic agents, cellular therapies and monoclonal antibodies will be required to effectively treat patients with myeloproliferative neoplasms.
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With an understanding of the molecular changes that accompany cell transformation, cancer drug discovery has undergone a dramatic change in the past few years. Whereas most of the emphasis in the past has been placed on developing drugs that induce cell death based on mechanisms that do not discriminate between normal and tumor cells, recent strategies have emphasized targeting specific mechanisms that have gone awry in tumor cells. ⋯ This review highlights a few important examples each of these types of therapies, along with some newer agents that are in various stages of development. Second-generation kinase inhibitors aimed at overriding emerging resistance to these therapies are also discussed.
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Patients with pancreatic cancer normally present with advanced disease that is lethal and notoriously difficult to treat. However, clinical developments over the past decade have been modest and advances are incremental at most. The core drug and the backbone of treatment in all settings of pancreatic adenocarcinoma-adjuvant, locally advanced, and metastatic-remains gemcitabine. ⋯ Although laboratory results of targeted therapies have been impressive, until now only erlotinib, an epidermal growth factor receptor tyrosine kinase inhibitor, has demonstrated marginal survival benefit in combination with gemcitabine in phase III clinical trials. Even though the failures of targeted therapies in the clinical setting are discouraging, it is reasonable to surmise that major progress will evolve as the molecular biology of pancreatic adenocarcinoma continues to be unraveled. This review describes some of the important developments and targeted agents for pancreatic cancer that have been tested in clinical trials.
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Review Case Reports
Head and neck squamous cell carcinoma: new translational therapies.
Head and neck squamous cell carcinoma includes cancers of the mouth, throat, larynx, and lymph nodes of the neck. Although early disease is amenable to single-modality treatment with surgery or radiation, patients with advanced disease have a dramatically worse prognosis, despite potentially morbid/toxic treatment regimens involving surgery, radiation, chemotherapy, or all 3 modalities. ⋯ Despite the many potentially promising avenues of head and neck squamous cell carcinoma research, only 2 new treatment approaches (antiepidermal growth factor receptor therapy and robotic surgery) have been approved by the US Food and Drug Administration in the past 30 years. Focused research programs involving integrated teams of clinicians, basic scientists, and translational clinician-researchers have the potential to accelerate discovery and change treatment paradigms for patients with head and neck cancer.
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Melanoma immunotherapy has been an area of intense research for decades, and this work is now yielding more tangible results for patients. Work has focused on 4 main areas: cytokine therapy, administration of immune-modulating antibodies, adoptive T-cell therapy, and vaccines. Cytokine therapy is an established treatment for advanced melanoma, and immune-modulating antibodies have recently emerged as an exciting new area of drug development with efficacy now established in a phase III trial. ⋯ A review of the field of melanoma immunotherapy is provided here, with emphasis on those agents that have reached clinical testing. Novel strategies to induce the immune system to attack melanomas are reviewed. In the future, it is envisioned that immunotherapy will have further application in combination with cytotoxic and targeted therapies.