The management of CLL has undergone unprecedented changes over the last decade. Modern targeted therapies are incorporated into clinical practice. Unfortunately, patients have begun to develop resistance or intolerance to multiple classes. Symptomatic patients previously treated with a BTK inhibitor and venetoclax represent a new and rapidly growing unmet need in CLL. Here we define unmet needs in a modern treatment context. We also critically review the literature for PI3K inhibitors and chemoi...
#2Lakshmi Muthuswamy(BIDMC: Beth Israel Deaconess Medical Center)H-Index: 16
Last. Manuel Hidalgo(CU: Cornell University)H-Index: 106
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Purpose null Pancreatic ductal adenocarcinoma (PDAC) remains a significant health issue. For most patients there are no options for targeted therapy and existing treatments are limited by toxicity. The HOPE trial (Harnessing Organoids for PErsonalized Therapy) was a pilot feasibility trial aiming to prospectively generate patient derived organoids (PDOs) from patients with PDAC and test their drug sensitivity and correlation with clinical outcomes. null Experimental design null PDOs were establi...
Last. Paul K. Paik(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 35
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PURPOSE Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups. PATIENTS AND METHODS This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoin...
Purpose null To evaluate the association between neutrophil-to-lymphocyte ratio (NLR) and efficacy of avelumab plus axitinib or sunitinib. null Experimental design null Adult patients with untreated advanced renal cell carcinoma (RCC) with a clear-cell component, {greater than or equal to}1 measurable lesion, Eastern Cooperative Oncology Group performance status of 0 or 1, fresh or archival tumor specimen, and adequate renal, cardiac, and hepatic function were included. Retrospective analyses of...
PURPOSE Less than 50% of patients with melanoma respond to anti-PD1, and this treatment can induce severe toxicity. Predictive markers are thus needed to improve the benefit/risk ratio of immune checkpoint inhibitors (ICI). Baseline tumor parameters such as PD-L1 expression, CD8+ T cell infiltration, mutational burden and various transcriptomic signatures are associated with response to ICI but their predictive values are not sufficient. Interaction between PD1 and its main ligand, PDL1 appears ...
IFN-γ is a cytokine produced by a restricted number of immune cells that acts on every nucleated cell type. Consistent with this remarkably wide spectrum of targets, the effects of IFN-γ are highly pleiotropic. On cells of the immune system, IFN-γ signaling has generally a pro-inflammatory effect, coordinating the innate and adaptive responses. On non-immune cells, IFN-γ tends to exert the opposite effect, it inhibits cell proliferation, induces cell death and, in addition, promotes their recogn...
#2Peronne Joseph(CWRU: Case Western Reserve University)H-Index: 8
Last. Vinay Varadan(CWRU: Case Western Reserve University)H-Index: 22
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Purpose null VSIR is a novel immune checkpoint protein whose expression on tumor cells across cancers remains largely uncharacterized. Here we purposed to decode the pan-cancer biologic and clinical significance of VSIR over-expression in the tumor compartment. null Experimental design null We performed multi-omics integrative analyses of 9735 tumor samples to identify cancers with non-leukocytic expression of VSIR (VSIR-High), followed by association with overall survival and immune cell infilt...
Last. Richard O. Hynes(MIT: Massachusetts Institute of Technology)H-Index: 159
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PURPOSE There is an unmet need for identifying novel biomarkers in Barrett's esophagus (BE) that could stratify patients with regards to neoplastic progression. We investigate the expression patterns of extracellular matrix (ECM) molecules in BE and BE-related neoplasia, and assess their value as biomarkers for the diagnosis of BE-related neoplasia and to predict neoplastic progression. EXPERIMENTAL DESIGN Gene expression analyses of ECM matrisome gene sets were performed using publicly availabl...
Purpose: Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. Experimental Design: We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of immunohistochemical stainings. Gene...
Last. Lukas M. Carter(MSK: Memorial Sloan Kettering Cancer Center)H-Index: 13
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PURPOSE Abnormal Notch signaling promotes cancer cell growth and tumor progression in various cancers. Targeting γ-secretase, a pivotal regulator in the Notch pathway, has yielded numerous γ-secretase inhibitors (GSIs) for clinical investigation in the last 2 decades. However, GSIs have demonstrated minimal success in clinical trials in part due to the lack of specific and precise tools to assess γ-secretase activity and its inhibition in vivo. EXPERIMENTAL DESIGN We designed an imaging probe ba...
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