Current opinion in oncology
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The purpose of this review is to provide an update on the current data about low-dose computed tomography (LD-CT) lung cancer screening. ⋯ Currently, the NLST is the only sufficiently powered trial to report a lower mortality rate with LD-CT screening. Long-term follow-up data are still anticipated on the European screening trials. Furthermore, data on the extent of the potential dangers of LD-CT screening, such as overdiagnosis, false-positive results, and the effect of cumulative radiation dose, have yet to be investigated thoroughly.
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BRAF and NRAS mutations can exert an oncogenic effect and are a target for novel therapeutic strategies. Selective MEK inhibitors inhibit growth and induce cell death in BRAF and NRAS mutated melanoma cell lines. The first MEK inhibitor (trametinib) has recently been approved for the treatment of BRAF-mutated metastatic melanoma not previously treated with BRAF inhibitors and several more are in clinical development. ⋯ MEK inhibitors represent a new treatment option in BRAF and NRAS mutated melanoma. As monotherapy, MEK inhibitors appear to provide minimal benefit in patients previously treated with a BRAF inhibitor, so they should be reserved for BRAF-inhibitor-naïve patients. Combined BRAF and MEK inhibition seems to provide a greater benefit than BRAF inhibitor monotherapy. MEK inhibition has also shown efficacy in NRAS-mutated patients, for whom there is no specific targeted therapy.
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Review
The perspective of immunotherapy: new molecules and new mechanisms of action in immune modulation.
Targeting CTLA-4, the patriarch of immune checkpoint modulators, is currently the only immunotherapeutic approach that has achieved significant clinical benefit in melanoma phase III trials. In this review, recent new ideas about the mechanism of action of anti-CTLA antibodies, other new molecules to target, and rationales for combination therapies will be discussed. ⋯ Immune checkpoint blockade is currently the most promising systemic therapeutic approach to achieve long-lasting responses or even cure in melanoma and other malignancies.
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To review and summarize the available evidence on factors predicting prognosis of children with relapsed acute lymphoblastic leukemia (ALL) and on the currently used treatment strategies, as well as on the most promising and innovative molecular or cellular therapies. ⋯ A significant proportion of children with relapsed ALL are salvaged by risk-oriented therapies. Novel agents should be integrated into combination regimens with the aim of further improving outcome of patients.
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Glial tumors of the central nervous system (CNS) are the leading cause of cancer-related death and morbidity in children. Their diagnosis/prognosis relies mainly on clinical and histopathological factors. However, pathological grading is particularly challenging as there is substantial molecular heterogeneity in pediatric CNS tumors, which results in variable biological behavior in tumors with potentially identical histological diagnoses or limited reliable measures of classification for given subgroups. Novel molecular markers/pathways identified by integrated genomic/transcriptomic/epigenomic studies of cohorts of pediatric gliomas are revolutionizing this field and are summarized herein. ⋯ Reappraisal of glioma classification using these novel biomarkers will likely change practice toward molecular pathology and their integration into clinical trials will enable personalized therapies based on the molecular fingerprint of individual tumors.