Pascal Janne
Université catholique de Louvain
CancerPathologyLung cancerCancer researchMedicine
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Publications 842
#1Zhi Wei Zhou (UTSW: University of Texas Southwestern Medical Center)H-Index: 1
#2Chiara Ambrogio (Harvard University)H-Index: 21
Last. Kenneth D. Westover (UTSW: University of Texas Southwestern Medical Center)H-Index: 27
view all 7 authors...
RAS proteins are guanosine triphosphatases (GTPases) that function as binary switches cycling between inactive (GDP-bound) and active (GTP-bound) states. Activated RAS proteins bind RAS effectors including RAF kinases, PI3K, RalGDS, and others. Conversion from GDP to GTP is stimulated by guanine nucleotide exchange factors (GEFs) while conversion to the inactive GDP-bound form is mediated by GTPase activating proteins (GAPs). Mutations can alter the signaling properties of RAS proteins through a...
#1Alissa J. Cooper (Brigham and Women's Hospital)
#2Yoshihisa Kobayashi (Harvard University)H-Index: 13
Last. Tom Nguyen (Harvard University)H-Index: 5
view all 16 authors...
PURPOSE: We pursued genomic analysis of an exceptional responder with non-small cell lung cancer (NSCLC) through a multi-platform effort to discover novel oncogenic targets. EXPERIMENTAL DESIGN: In this open-label, single-arm phase II study (NCT01829217), an enriched cohort of patients with advanced NSCLC were treated with the multi-kinase inhibitor sunitinib. The primary endpoint was objective response rate. Tissue was collected for multi-platform genomic analysis of responders, and a candidate...
#1Junji Tsurutani (Kindai University)H-Index: 26
#2Hiroji IwataH-Index: 47
Last. Trisha Michel Wise-Draper (UC: University of Cincinnati)H-Index: 12
view all 16 authors...
HER2-targeted therapies are approved only for HER2-positive breast and gastric cancers. We assessed the safety/tolerability and activity of the novel HER2-targeted antibody–drug conjugate trastuzumab deruxtecan (T-DXd) in 60 patients with pretreated, HER2-expressing (IHC ≥ 1+), non-breast/non-gastric or HER2-mutant solid tumors from a phase I trial (NCT02564900). Most common (>50%) treatment-emergent adverse events (TEAE) were nausea, decreased appetite, and vomiting. Two drug-related TEAEs were...
1 CitationsSource
#1Atsuko Ogino (Harvard University)H-Index: 10
#2Jihyun Choi (Harvard University)H-Index: 2
Last. Mohit Butaney (Harvard University)H-Index: 18
view all 17 authors...
Small cell lung cancer (SCLC) occurs infrequently in never/former light smokers. We sought to study this rare clinical subset through next generation sequencing (NGS) and by characterizing a representative patient derived model. We performed targeted NGS, as well as comprehensive pathological evaluation, in 11 never/former light smokers with clinically diagnosed SCLC. We established a patient derived model from one such patient (DFCI168) harboring an NRAS(Q61K) mutation and characterized the sen...
#1Stephanie Guerra (Harvard University)H-Index: 3
#2Ophélia Maertens (Harvard University)H-Index: 8
Last. Man XuH-Index: 3
view all 15 authors...
Summary While KRAS mutations are common in non-small cell lung cancer (NSCLC), effective treatments are lacking. Here, we report that half of KRAS-mutant NSCLCs aberrantly express the homeobox protein HOXC10, largely due to unappreciated defects in PRC2, which confers sensitivity to combined BET/MEK inhibitors in xenograft and PDX models. Efficacy of the combination is dependent on suppression of HOXC10 by BET inhibitors. We further show that HOXC10 regulates the expression of pre-replication co...
#2Yanan KuangH-Index: 19
Last. Bohdan PomahacH-Index: 29
view all 9 authors...
#1Elena Ivanova (Harvard University)H-Index: 25
#2Mari Kuraguchi (Harvard University)H-Index: 12
Last. Shuai Li (Harvard University)H-Index: 6
view all 22 authors...
Purpose: Evaluating drug responses using primary patient derived cells ex vivo represents a potentially rapid and efficient approach to screening for new treatment approaches. Here, we sought to identify neratinib combinations in HER2mutant non-small cell lung cancer (NSCLC) patient xenograft derived organotypic spheroids (XDOTS) using a short term ex vivo system. Experimental Design: We generated two HER2 mutant NSCLC PDX models (DFCI359 (HER2 exon19 755_757LREdelinsRP) and DFCI315 (HER2 exon20...
#1Gonzalo Recondo (Harvard University)H-Index: 4
#1G. Recondo (Harvard University)
Last. Tom NguyenH-Index: 5
view all 23 authors...
Purpose: Molecular mechanisms of acquired resistance to MET TKIs are poorly understood. We aimed to characterize the genomic mechanisms of resistance to type I and type II MET TKIs and their impact on sequential MET TKI therapy outcomes in patients with metastatic MET exon 14 mutant NSCLC. Experimental Design: Genomic alterations occurring at the time of progression on MET TKIs were studied using plasma and tissue next-generation sequencing (NGS). Results: A total of 20 patients had tissue or pl...
#1Jacob Sands (Harvard University)H-Index: 1
#2Tom Nguyen (Harvard University)H-Index: 5
Last. Lynette M. Sholl (Brigham and Women's Hospital)H-Index: 43
view all 10 authors...
Abstract Objectives Potentially targetable genomic alterations have been identified in lung squamous cell carcinoma (LUSC), but none have yet translated into effective therapy. We examined potential benefits of next generation sequencing (NGS) in a cohort of consecutive LUSC patients with emphasis on distinctions between smokers and light/never smokers and implications for clinical trial enrollment. Methods We retrospectively evaluated results from an internally developed NGS assay (OncoPanel) t...