1. P856 : a single-cell functional precision medicine landscape of multiple myelomaKlara Kropivšek, Paul Kachel, Sandra Goetze, Rebekka Wegmann, Yannik Severin, Benjamin D. Hale, Yasmin Festl, Julien Mena, Audrey Van Drogen, Nadja Dietliker, 2022, published scientific conference contribution abstract Abstract: Multiple myeloma (MM) is a cancer of plasma cells, defined by complex genetics and extensive intra- and inter-patient heterogeneity. Despite improved patient survival driven by a plethora of treatment options, the disease remains incurable.
Molecularly-guided precision medicine to individualize treatment strategies in MM has had limited success, in part due to the genetic and molecular complexity of the disease. Functional precision medicine, a complementary approach in which patient treatment is guided by the ex vivo drug response of patient cells, has not yet been evaluated for MM systematically. Keywords: mutliple myeloma, hematology, precision medicine, microscopy, deep learning, phenotyping, oncology, proteotype Published in RUNG: 11.11.2024; Views: 446; Downloads: 4
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2. Ex vivo drug response heterogeneity reveals personalized therapeutic strategies for patients with multiple myelomaKlara Kropivšek, Paul Kachel, Sandra Goetze, Rebekka Wegmann, Yasmin Festl, Yannik Severin, Benjamin D. Hale, Julien Mena, Audrey Van Drogen, Nadja Dietliker, 2023, original scientific article Abstract: Abstract
Multiple myeloma (MM) is a plasma cell malignancy defined by complex genetics and extensive patient heterogeneity. Despite a growing arsenal of approved therapies, MM remains incurable and in need of guidelines to identify effective personalized treatments. Here, we survey the ex vivo drug and immunotherapy sensitivities across 101 bone marrow samples from 70 patients with MM using multiplexed immunofluorescence, automated microscopy and deep-learning-based single-cell phenotyping. Combined with sample-matched genetics, proteotyping and cytokine profiling, we map the molecular regulatory network of drug sensitivity, implicating the DNA repair pathway and EYA3 expression in proteasome inhibitor sensitivity and major histocompatibility complex class II expression in the response to elotuzumab. Globally, ex vivo drug sensitivity associated with bone marrow microenvironmental signatures reflecting treatment stage, clonality and inflammation. Furthermore, ex vivo drug sensitivity significantly stratified clinical treatment responses, including to immunotherapy. Taken together, our study provides molecular and actionable insights into diverse treatment strategies for patients with MM. Keywords: ultiple myeloma, precision medicine, ex-vivo, pharmacoscopy, proteotyping, oncology, hematology, microscopy, drug score Published in RUNG: 11.11.2024; Views: 456; Downloads: 5
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