ORCID Profile
0000-0002-4548-2766
Current Organisations
National Cancer Centre Singapore
,
Duke-NUS Medical School
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Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480718
Abstract: Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Publisher: American Association for Cancer Research (AACR)
Date: 14-07-2021
DOI: 10.1158/1078-0432.CCR-20-4607
Abstract: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFRT790M-negative resistance. We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M+) and -negative (T790M−) disease. Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M− tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal lifications, whole-genome doubling and nonaging mutational signatures in T790M− tumors. Almost half of resistant tumors were further classified as immunehot, with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M− and T790M+ disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping ergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480712.V1
Abstract: Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480718.V1
Abstract: Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480715
Abstract: Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480715.V1
Abstract: Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530516
Abstract: AbstractPurpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in i EGFR /i -mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in i EGFR /i sup T790M /sup -negative resistance. Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic i EGFR /i -mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M sup + /sup ) and -negative (T790M sup − /sup ) disease. Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M sup − /sup tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as i TP53 /i alterations, 3q chromosomal lifications, whole-genome doubling and nonaging mutational signatures in T790M sup − /sup tumors. Almost half of resistant tumors were further classified as immune sup hot /sup , with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M sup − /sup and T790M sup + /sup disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. Conclusions: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping ergent TKI resistance and outcome trajectories in i EGFR /i -mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential. /
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.22480712
Abstract: Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities
Publisher: American Association for Cancer Research (AACR)
Date: 31-03-2023
DOI: 10.1158/1078-0432.C.6530516.V1
Abstract: AbstractPurpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in i EGFR /i -mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in i EGFR /i sup T790M /sup -negative resistance. Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic i EGFR /i -mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M sup + /sup ) and -negative (T790M sup − /sup ) disease. Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M sup − /sup tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as i TP53 /i alterations, 3q chromosomal lifications, whole-genome doubling and nonaging mutational signatures in T790M sup − /sup tumors. Almost half of resistant tumors were further classified as immune sup hot /sup , with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M sup − /sup and T790M sup + /sup disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naïve patients. Conclusions: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping ergent TKI resistance and outcome trajectories in i EGFR /i -mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential. /
No related grants have been discovered for Lisda Suteja.