Current opinion in oncology
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There is increasing molecular and epidemiologic evidence that human papillomavirus (HPV) is associated with a distinct subset of head and neck squamous cell carcinomas. The strength and consistency of HPV DNA presence in oropharyngeal cancers bolster the argument that this association is likely causal. HPV-positive tonsillar cancer in particular is emerging as a specific disease entity with distinct molecular, pathologic, and clinical characteristics. ⋯ This review focuses on the recent literature (since 1998) investigating the relationship between HPV and head and neck cancer development, using the current paradigm for causal inference in epidemiologic research attributed to Sir A. Bradford Hill. Data examining the association of HPV with pathogenesis of head and neck squamous cell carcinoma before 1999 were previously reviewed in this journal.
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In the past decade, the discovery of tumor antigens recognized by T cells has revolutionized the tumor vaccine field. The appreciation that peptides are bound to and restricted by major histocompatibility class I and II molecules for immune recognition has encouraged a number of early-phase clinical trials of peptide vaccines. I summarize herein the rationale for and the results of a number of clinical trials of peptide vaccines for melanoma, suggesting that immune and clinical responses can be seen in those with metastatic and resected disease using a variety of surrogate assays. The challenge for the future is to correlate the results of immunologic assays with clinical benefit in patients with advanced cancer.
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The bcr-abl fusion protein is present in the vast majority of cases of chronic myelogenous leukemia, and the deregulated tyrosine kinase activity of this protein is essential for leukemic transformation. Thus, bcr-abl is an ideal target for pharmacologic inhibition. In preclinical studies, ST1571 (formerly CGP57148B), an abl-specific, tyrosine kinase inhibitor, selectively killed bcr-abl-expressing cells both in vitro and in vivo. In early clinical trials of ST1571, encouraging results have been obtained, and there is already a suggestion that ST1571 may soon need to be incorporated into treatment algorithms for chronic myelogenous leukemia.
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The past year has seen a greater understanding of the means by which the alveolar rhabdomyosarcoma gene fusions (PAX-FKHR) lead to the malignant phenotype. The treatment of the primary tumor in rhabdomyosarcoma has been reexamined, with the roles of surgery and radiation expanding in American studies and decreasing in European ones. "Megatherapy" approaches with stem cell or bone marrow autologous transplants still have not found a role in the treatment of metastatic rhabdomyosarcoma. Our understanding of the natural history of nonrhabdo soft tissue sarcomas in children has increased, and molecular diagnosis is becoming established. The role of chemotherapy in treatment remains controversial.
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The occurrence of undesirable side effects due to opioids (delirium, confusion, myoclonus, nausea, emesis) is one of the major complications in the management of pain, especially in chronic cancer pain states. Methadone, as an alternative to morphine, has been proposed in the control of opioid-induced toxicity. ⋯ Aspects of its pharmacology, indications, and switching modalities are discussed here. Opioid rotation is a new tool in the management of cancer pain, deserving more attention.