Hematology/oncology clinics of North America
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Hematol. Oncol. Clin. North Am. · Aug 2017
ReviewMechanisms of Resistance to FLT3 Inhibitors and the Role of the Bone Marrow Microenvironment.
The presence of FLT3 mutations in acute myeloid leukemia (AML) carries a particularly poor prognosis, making the development of FLT3 inhibitors an imperative goal. The last decade has seen an abundance of clinical trials using these drugs alone or in combination with chemotherapy. ⋯ Initial success has been followed by the emergence of clinical resistance. Although novel FLT3 inhibitors are being developed, studies into mechanisms of resistance raise hope of new strategies to prevent emergence of resistance and eliminate minimal residual disease.
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Hematol. Oncol. Clin. North Am. · Jun 2017
ReviewUpdate on Gastroesophageal Adenocarcinoma Targeted Therapies.
Gastroesophageal cancer (GEC) remains a major cause of cancer-related mortality worldwide. Although the incidence of distal gastric adenocarcinoma (GC) is declining in the United States, proximal esophagogastric junction adenocarcinoma (EGJ) incidence is rising. ⋯ Overall survival in the metastatic setting remains poor, with few molecular targeted approaches having been successfully incorporated into routine care to date-only first-line anti-HER2 therapy for ERBB2 amplification and second-line anti-VEGFR2 therapy. This article reviews aberrations in epidermal growth factor receptor, MET, and ERBB2, their therapeutic implications, and future directions in targeting these pathways.
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Hematol. Oncol. Clin. North Am. · Feb 2017
ReviewDiagnosis and Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small Cell Lung Cancer.
Anaplastic lymphoma kinase (ALK) gene rearrangements occur in a small portion of patients with non-small cell lung cancer (NSCLC). These gene rearrangements lead to constitutive activation of the ALK kinase and subsequent ALK-driven tumor formation. ⋯ Resistance to these kinase inhibitors occurs through several mechanisms, resulting in ongoing clinical challenges. This review summarizes the biology of ALK-positive lung cancer, methods for diagnosing ALK-positive NSCLC, current FDA-approved ALK inhibitors, mechanisms of resistance to ALK inhibition, and potential strategies to combat resistance.
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With the implementation of genomic technologies into clinical practice, we have examples of the predictive benefit of targeted therapy for oncogene-addicted cancer and identified molecular dependencies in non-small cell lung cancer. The clinical success of tyrosine kinase inhibitors against epidermal growth factor receptor and anaplastic lymphoma kinase activation has shifted treatment emphasize the separation of subsets of lung cancer and genotype-directed therapy. Advances have validated oncogenic driver genes and led to the development of targeted agents. This review highlights treatment options, including clinical trials for ROS1 rearrangement, RET fusions, NTRK1 fusions, MET exon skipping, BRAF mutations, and KRAS mutations.
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Hematol. Oncol. Clin. North Am. · Oct 2016
ReviewUse of Direct Oral Anticoagulants in Special Populations.
Direct oral anticoagulants (DOACs) have been approved for the treatment of venous thromboembolism and atrial fibrillation based on randomized controlled trials (RCTs) of direct comparisons with vitamin K antagonists. Despite having more than 100,000 patients enrolled, safety and efficacy are debated in selected populations. Although DOACs are reviewed as a class of anticoagulant, pharmacokinetic differences exist such that different medications may be beneficial in distinct clinical settings. Synthesizing available evidence based on phase III RCTs, post hoc subgroup analyses, and pooled metaanalyses, this review provides an overview of DOACs and scrutinizes individual differences in their applications for the special populations.