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Transmissible leukemia-like cancer in the marine species Cerastoderma edule and Mya arenaria is characterized by long-term tolerance as well as genomic instability.
In delineating scientific findings, authors should avoid assertions of primacy and novelty, in favor of measured descriptions of advance and potential importance for the field.
Transmissible cancer affects marine bivalve mollusks worldwide, but how genetic mechanisms influence cancer evolution and disease spread remains largely unexplored. Two new studies provide insights into the ancient origin of founder clones and the long-term tolerance of contagious cancer cells to extreme genome instability.
Certain cancers disrupt metabolism, leading to the wasting syndrome known as cachexia. How tumor-induced mediators of cachexia induce changes in end organs is unclear. A study implicates the endothelium as an amplifier of tumor signals in fat, in which NOTCH1 promotes adipose tissue remodeling via retinoic acid, IL-33 and IGFBP3.
Chimeric antigen receptor T cells and T cell-redirecting bispecific antibody therapies are changing the landscape of myeloma therapy. Two studies investigate the genetic and epigenetic resistance mechanisms that lead to relapse in patients receiving T cell-engaging therapies targeting B cell maturation antigen (BCMA) and GPRC5D.
Derrien et al. analyze three patients relapsing on talquetamab, a bispecific antibody against CD3 and GPRC5D, and show that acquired resistance is mediated by genetic inactivation or by long-range epigenetic silencing of GPRCD5.
Taylor et al. show that tumor cells promote white adipose tissue (WAT) wasting and cachexia by overactivation of Notch1 signaling and retinoic acid production in distant WAT endothelium, which can be therapeutically targeted to inhibit wasting.
Hart et al. study the transmissible marine leukemia of the soft-shell clam Myaarenaria and focus on a cancer lineage that is characterized by varied genomic instability as well as a mutational signature that includes an error-prone polymerase.
Bruzos et al. analyze >6,800 samples of Cerastoderma edule, generate a reference genome and follow the evolution of bivalve transmissible neoplasia that infects them. They find two lineages that show genomic instability but also long-term tolerance.
Wiita and colleagues use cross-linking mass spectrometry and glycoprotein surface capture to identify an activated conformation of integrin β2 present on AML cells and develop CAR T cells that target this conformation antigen in preclinical models.