Cancer discovery
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Activating KRAS mutations are found in nearly all cases of pancreatic ductal adenocarcinoma (PDAC), yet effective clinical targeting of oncogenic KRAS remains elusive. Understanding of KRAS-dependent PDAC-promoting pathways could lead to the identification of vulnerabilities and the development of new treatments. We show that oncogenic KRAS induces BNIP3L/NIX expression and a selective mitophagy program that restricts glucose flux to the mitochondria and enhances redox capacity. ⋯ SIGNIFICANCE: NIX-mediated mitophagy is a new oncogenic KRAS effector pathway that suppresses functional mitochondrial content to stimulate cell proliferation and augment redox homeostasis. This pathway promotes the progression of PanIN to PDAC and represents a new dependency in pancreatic cancer. This article is highlighted in the In This Issue feature, p. 1143.
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Patients with non-small cell lung cancer harboring MET exon 14 skipping mutations have commonly been treated with the multikinase inhibitor crizotinib, but more MET-specific therapies are being developed. Two such agents, capmatinib and tepotinib, have demonstrated preliminary efficacy in ongoing phase II trials.
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Autologous immune cells genetically engineered to target B-cell maturation antigen can help patients with relapsed or refractory multiple myeloma achieve deep molecular remissions with minimal neurotoxicity, according to initial data from a phase I trial.
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Oncologists are testing fecal transplants and other microbiome-based products in combination with checkpoint inhibitors in an effort to increase and enhance responses. However, questions remain about how the microbes affect host immunity and which preparations of bacteria are optimal.
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The anti-CD47 drug Hu5F9-G4, also known as 5F9, in combination with the anti-CD20 therapy rituximab, may be a promising treatment for some forms of non-Hodgkin lymphoma because it allows macrophages to recognize and attack cancer cells. In a phase Ib trial testing the combination, patients with relapsed/refractory diffuse large B-cell lymphoma or follicular lymphoma had an objective response rate of 50% and few side effects.