The Mount Sinai journal of medicine, New York
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Lung cancer is currently the leading cause of cancer-related death in the United States and worldwide, accounting for approximately a third of all cancer diagnoses and deaths. The American Cancer Society estimates 159,390 deaths from lung cancer in the United States for 2009 alone. The high mortality rate associated with lung cancer has prompted numerous exhaustive efforts to identify novel therapeutic targets and treatment modalities for this deadly disease. ⋯ Despite these successes, de novo or acquired resistance to these anti-epidermal growth factor receptor agents invariably develops, either through additional mutations in the epidermal growth factor receptor, or abnormal regulation of downstream signaling pathways. Thus, it is necessary to further investigate the molecular determinants of treatment resistance and to develop novel therapeutic strategies directed specifically against the molecular drivers of metastatic chemoresistant lung cancer. Given the heterogeneity and convergence of signaling pathways underlying both disease etiology and chemoresistance, future efforts to administer rationally designed agents against multiple molecular targets could serve to improve both first-line and second-line therapies for patients with lung adenocarcinoma.
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Malignant gliomas are the most common primary brain tumors in adults and carry a dismal prognosis. Despite aggressive therapy with maximal safe surgical resection, radiation and chemotherapy, these tumors invariably are refractory to or become resistant to treatment and recur. Gliomas are highly infiltrative cancers and display remarkable genetic heterogeneity making them challenging to treat. ⋯ In addition, the growing body of research in cancer immunology as well as cancer stem cells has made inroads in our understanding of tumorgenesis. Translational research has been particularly crucial to the development of these therapies as much preclinical and clinical work is needed to develop the rationale for treatments, to develop biomarkers of drug activity and to elucidate mechanisms of resistance. This brief overview will discuss some of the pivotal advances made in the pursuit of improved outcomes and survival for patients with this devastating disease.
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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.