The lancet oncology
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The lancet oncology · Nov 2008
ReviewClinical potential of mucins in diagnosis, prognosis, and therapy of ovarian cancer.
Knowledge of mucins and their multiple roles in various normal and pathological processes has improved greatly in the past two decades. Mucins belong to a family of glycoproteins characterised by densely O-glycosylated repetitive domains and expressed by various surface epithelial cells. Altered expression of mucins is present in various diseases, including cancer. ⋯ Therefore, improved strategies for early diagnosis and treatment are needed. Because of the surface epithelial origin of epithelial ovarian cancer, mucins are obvious biomolecules for investigation as markers for early diagnosis and as therapeutic targets. We discuss the potential role and clinical usefulness of mucins in early diagnosis, prognosis, and treatment of ovarian cancer.
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The lancet oncology · Oct 2008
Review Meta AnalysisAssessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer.
Somatic mutations of the k-RAS oncogene have been assessed as a mechanism of de-novo resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC), and to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). The aim of this systematic review and meta-analysis was to assess if k-RAS mutations represent a candidate predictive biomarker for anti-EGFR-targeted therapeutic strategies in mCRC and NSCLC. ⋯ This analysis provides empirical evidence that k-RAS mutations are highly specific negative predictors of response (de-novo resistance) to single-agent EGFR TKIs in advanced NSCLC; and similarly to anti-EGFR monoclonal antibodies alone or in combination with chemotherapy in patients with mCRC. The low sensitivity and relatively high -LR of k-RAS mutations for determining non-responsiveness clearly shows that additional mechanisms of resistance to EGFR inhibitors exist.
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The lancet oncology · Oct 2008
Review Meta AnalysisAssessment of somatic k-RAS mutations as a mechanism associated with resistance to EGFR-targeted agents: a systematic review and meta-analysis of studies in advanced non-small-cell lung cancer and metastatic colorectal cancer.
Somatic mutations of the k-RAS oncogene have been assessed as a mechanism of de-novo resistance to epidermal growth factor receptor (EGFR) tyrosine-kinase inhibition in patients with non-small-cell lung cancer (NSCLC), and to anti-EGFR monoclonal antibodies in patients with metastatic colorectal cancer (mCRC). The aim of this systematic review and meta-analysis was to assess if k-RAS mutations represent a candidate predictive biomarker for anti-EGFR-targeted therapeutic strategies in mCRC and NSCLC. ⋯ This analysis provides empirical evidence that k-RAS mutations are highly specific negative predictors of response (de-novo resistance) to single-agent EGFR TKIs in advanced NSCLC; and similarly to anti-EGFR monoclonal antibodies alone or in combination with chemotherapy in patients with mCRC. The low sensitivity and relatively high -LR of k-RAS mutations for determining non-responsiveness clearly shows that additional mechanisms of resistance to EGFR inhibitors exist.
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Apoptosis is a fundamental process in the development and maintenance of multicellular organisms and its regulation is commonly disrupted in human cancers. In vitro and in vivo, effective treatment of cancer with radiotherapy or anticancer drugs (or both) is frequently associated with increased markers of apoptosis. ⋯ With increased understanding of the regulatory and effector molecules of apoptosis new drugs have been developed that might manipulate the apoptotic balance in cancer cells in favour of cell death. This Review summarises the rationale for direct manipulation of various elements of apoptosis and describes agents that are currently under investigation in early-phase clinical trials in many different cancer types.
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The lancet oncology · Sep 2008
Review Comparative StudyBone-marrow relapse in paediatric acute lymphoblastic leukaemia.
Marrow relapse is the major obstacle to cure for 10-15% of young patients with acute lymphoblastic leukaemia (ALL). Recent investigations into the biology of minimal residual disease indicate that many early relapses derive from residual cells present at first diagnosis, but some late relapses might represent new mutations in leukaemic cells not eliminated by conventional therapy. Treatment of marrow relapse involves higher doses and more intensive schedules of the drugs used for initial therapy with or without haemopoietic stem cell transplantation. ⋯ Understanding the molecular biology of ALL underlies development of improved risk stratification and new therapies. Although better drugs are needed, introduction of new agents into clinical trials in paediatric disease has been difficult. Innovative trial designs and use of valid surrogate endpoints may expedite this process.