Cancer discovery
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A case report highlights a novel, rare mechanism of resistance to chimeric antigen receptor (CAR) T-cell therapy, conferred by the accidental transduction of a single leukemic B cell with the anti-CD19 CAR (CAR19) gene during therapy manufacturing. Because CAR19 bound directly to CD19 on the cell surface-a phenomenon called in cis epitope masking-the therapeutic target was effectively hidden from reprogrammed T cells.
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On September 21, the Lasker Foundation bestowed its 2018 Albert Lasker Basic Medical Research Award on Michael Grunstein, PhD, and C. David Allis, PhD, for their discoveries explaining how gene expression is regulated by chemical modifications of histones.
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Findings from a 10-year clinical trial show improved survival rates among children with high-risk rhabdomyosarcoma who receive low-dose maintenance chemotherapy following standard treatment. The results have established a new standard of care for this disease in the EU.
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The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. The third-generation ALK inhibitor lorlatinib has demonstrated clinical activity in patients who failed previous ALK inhibitors. To define the spectrum of ALK mutations that confer lorlatinib resistance, we performed accelerated mutagenesis screening of Ba/F3 cells expressing EML4-ALK. ⋯ A more efficacious long-term strategy may be up-front treatment with a third-generation ALK inhibitor to prevent the emergence of on-target resistance. Cancer Discov; 8(6); 714-29. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 663.
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Findings from a phase I study indicate that the investigational RET inhibitor BLU-667 is safe and well tolerated, inducing good responses in patients with RET-altered medullary thyroid cancer or non-small cell lung cancer.