Key Points• This is the first study to validate the importance of NOTCH1 and SF3B1 gene mutations in the context of a randomized, prospective clinical trial.• Mutations in both genes are independent prognostic biomarkers, and therefore have clinical utility in the accurate risk-adapted stratification of CLL patients.
Continuing Medical Education onlineThis activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of Medscape, LLC and the American Society of Hematology. Medscape, LLC is accredited by the ACCME to provide continuing medical education for physicians. Medscape, LLC designates this Journal-based CME activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) ™ . Physicians should claim only the credit commensurate with the extent of their participationin the activity. All other clinicians completing this activity will be issued a certificate of participation. To participate in this journal CME activity: (1) review the learning objectives and author disclosures; (2) study the education content; (3) take the post-test with a 70% minimum passing score and complete the evaluation at http://www.medscape.org/journal/blood; and (4) view/print certificate. For CME questions, see page 566. Disclosures Associate Editor John G. Gribben served as an advisor or consultant for Celgene and Roche and as a speaker or a member of a speakers bureau for Roche, Jensen, and Celgene. The authors and CME questions author Laurie Barclay, freelance writer and reviewer, Medscape, LLC, declare no competing financial interests. For personal use only. on May 9, 2018. by guest www.bloodjournal.org From
Continuing Medical Education online Learning objectivesUpon completion of this activity, participants will be able to:1. Describe the frequency of NOTCH1 and SF3B1 mutations in patients with chronic lymphocytic leukemia (CLL), and their correlations with other genetic markers.2. Describe survival in CLL patients with NOTCH1 mutations, and the prognostic value of this mutation. 3. Describe survival in CLL patients with SF3B1 mutations, and the prognostic value of this mutation.
Cetuximab led to a significant increase in RR and OS in patients with KRAS/BRAF wild-type rectal cancer, but the primary end point of improved CR was not met.
The progressive elucidation of the molecular pathogenesis of cancer has fueled the rational development of targeted drugs for patient populations stratified by genetic characteristics. Here we discuss general challenges relating to molecular diagnostics and describe predictive biomarkers for personalized cancer medicine. We also highlight resistance mechanisms for epidermal growth factor receptor (EGFR) kinase inhibitors in lung cancer. We envisage a future requiring the use of longitudinal genome sequencing and other omics technologies alongside combinatorial treatment to overcome cellular and molecular heterogeneity and prevent resistance caused by clonal evolution.
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