Marcelo V. Negrão
A5022661673- Lung Cancer Treatments and Mutations
- Colorectal Cancer Treatments and Studies
- Cancer Genomics and Diagnostics
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- RNA modifications and cancer
- Chronic Lymphocytic Leukemia Research
- Lung Cancer Research Studies
- Cancer-related Molecular Pathways
- HER2/EGFR in Cancer Research
- Melanoma and MAPK Pathways
- Advanced Breast Cancer Therapies
- Cancer Mechanisms and Therapy
- Lung Cancer Diagnosis and Treatment
- Chromatin Remodeling and Cancer
- PI3K/AKT/mTOR signaling in cancer
- Computational Drug Discovery Methods
- Peptidase Inhibition and Analysis
- Immunotherapy and Immune Responses
- Acute Myeloid Leukemia Research
- Ferroptosis and cancer prognosis
- Mechanisms of cancer metastasis
- Radiomics and Machine Learning in Medical Imaging
- Gastric Cancer Management and Outcomes
- Brain Metastases and Treatment
The University of Texas MD Anderson Cancer Center
2017-2025
Thoracic Surgery Foundation
2022
Instituto do Câncer do Estado de São Paulo
2014-2020
Fistula Foundation
2020
Universidade de São Paulo
2010-2019
Associação de Assistência à Criança Deficiente
2017-2018
Hospital Sírio-Libanês
2017-2018
Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. Adagrasib showed clinical activity had an acceptable adverse-event profile the phase 1–1b part of KRYSTAL-1 1–2 study.
Abstract Purpose: Osimertinib was initially approved for T790M-positive non–small cell lung cancer (NSCLC) and, more recently, first-line treatment of EGFR-mutant NSCLC. However, resistance mechanisms to osimertinib have been incompletely described. Experimental Design: Using cohorts from The University Texas MD Anderson Lung Cancer Moonshot GEMINI and Moffitt Center databases, we collected clinical data patients treated with osimertinib. Molecular profiling analysis performed at the time...
Background Non-small cell lung cancer (NSCLC) patients bearing targetable oncogene alterations typically derive limited benefit from immune checkpoint blockade (ICB), which has been attributed to low tumor mutation burden (TMB) and/or PD-L1 levels. We investigated oncogene-specific differences in these markers and clinical outcome. Methods Three cohorts of NSCLC with (n=4189 total) were analyzed. Two advanced treated ICB monotherapy [MD Anderson (MDACC; n=172) Flatiron Health-Foundation...
IntroductionProgrammed death-ligand 1 (PD-L1) expression may vary in different disease sites and at time points of the course. We aimed to investigate PD-L1 heterogeneity its usefulness as a predictive value for immune checkpoint inhibitor (ICI) therapy patients with NSCLC.MethodsPD-L1 was analyzed 1398 NSCLC. The ICIs 398 metastatic NSCLC assessed.ResultsPD-L1 significantly associated biopsy (p = 0.004). Adrenal, liver, lymph node (LN) metastases had highest continuous variable 1% or 50%...
Acquired resistance to tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) remains a clinical challenge. Especially challenging are cases in which emerges through EGFR-independent mechanisms, such as pathways that promote epithelial-to-mesenchymal transition (EMT). Through an integrated transcriptomic, proteomic, and drug screening approach, we identified activation the yes-associated protein (YAP) forkhead box M1 (FOXM1) axis driver EMT-associated EGFR TKI...
Abstract Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding to neoadjuvant Nivo+CT is unknown. Here we report the results correlates two arms phase 2 platform NEOSTAR trial testing Ipi+Nivo+CT major (MPR) as primary endpoint. MPR were 32.1% (7/22, 80% confidence interval (CI) 18.7–43.1%) arm 50% (11/22, CI 34.6–61.1%) arm; endpoint...
Molecular modifiers of KRASG12C inhibitor (KRASG12Ci) efficacy in advanced KRASG12C-mutant NSCLC are poorly defined. In a large unbiased clinicogenomic analysis 424 patients with non-small cell lung cancer (NSCLC), we identified and validated coalterations KEAP1, SMARCA4, CDKN2A as major independent determinants inferior clinical outcomes KRASG12Ci monotherapy. Collectively, comutations these three tumor suppressor genes segregated into distinct prognostic subgroups captured ∼50% those early...
We report a phase II study of 50 advanced non-small cell lung cancer (NSCLC) patients with point mutations or insertions in EGFR exon 20 treated poziotinib (NCT03066206). The achieved its primary endpoint, confirmed objective response rates (ORRs) 32% and 31% by investigator blinded independent review, respectively, median progression-free survival 5.5 months. Using preclinical studies, silico modeling, molecular dynamics simulations, we found that sensitivity was highly dependent on the...
Only around 20-30% of patients with non-small-cell lung cancer (NCSLC) have durable benefit from immune-checkpoint inhibitors. Although tissue-based biomarkers (eg, PD-L1) are limited by suboptimal performance, tissue availability, and tumour heterogeneity, radiographic images might holistically capture the underlying biology. We aimed to investigate application deep learning on chest CT scans derive an imaging signature response immune checkpoint inhibitors evaluate its added value in...
Abstract Understanding the cellular processes that underlie early lung adenocarcinoma (LUAD) development is needed to devise intervention strategies 1 . Here we studied 246,102 single epithelial cells from 16 early-stage LUADs and 47 matched normal samples. Epithelial comprised diverse cancer cell states, diversity among was strongly linked LUAD-specific oncogenic drivers. KRAS mutant showed distinct transcriptional features, reduced differentiation low levels of aneuploidy. Non-malignant...
IntroductionThe combination of programmed cell death protein-1 or death-ligand 1 immune checkpoint blockade and chemotherapy has revolutionized the treatment advanced NSCLC, but mechanisms underlying this synergy remain incompletely understood. In study, we explored relationships between neoadjuvant microenvironment (IME) resectable NSCLC to identify novel by which may enhance effect blockade.MethodsGenomic, transcriptomic, profiling data 511 patients treated with followed surgery (NCT)...
PURPOSE Targeted therapies against non–small-cell lung cancer (NSCLC) harboring HER2 mutations remain an unmet need. In this study, we assessed the efficacy and safety of poziotinib in patients with exon 20 mutant advanced NSCLC a single-arm, open-label, phase II study. PATIENTS AND METHODS Patients were enrolled to receive at dose 16 mg/d for 28-day cycles. The primary end point was objective response rate per RECIST version 1.1. Confirmatory scans performed least 28 days from initial...
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary point, may be published when key planned co-primary or secondary analyses are not yet available. Trial Updates provide an opportunity to disseminate additional results from studies, in JCO elsewhere, for which point has already been reported.Patients with Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutated non-small-cell lung cancer (NSCLC) and...
Abstract The role of combination chemotherapy with immune checkpoint inhibitors (ICI) (ICI-chemo) over ICI monotherapy (ICI-mono) in non-small cell lung cancer (NSCLC) remains underexplored. In this retrospective study 1133 NSCLC patients, treatment ICI-mono vs ICI-chemo associate higher rates early progression, but similar long-term progression-free and overall survival. Sequential concurrent have survival, suggesting no synergism from therapy. Integrative modeling identified PD-L1, disease...
For patients with advanced non-small-cell lung cancer (NSCLC), dual immune checkpoint blockade (ICB) CTLA4 inhibitors and PD-1 or PD-L1 (hereafter, PD-(L)1 inhibitors) is associated higher rates of anti-tumour activity immune-related toxicities, when compared treatment alone. However, there are currently no validated biomarkers to identify which will benefit from ICB1,2. Here we show that NSCLC who have mutations in the STK11 and/or KEAP1 tumour suppressor genes derived clinical ICB...
Resistance to inactive state-selective RASG12C inhibitors frequently entails accumulation of RASGTP, rendering effective inhibition active RAS potentially desirable. Here, we evaluated the antitumor activity RAS(ON) multiselective tricomplex inhibitor RMC-7977 and dissected mechanisms response tolerance in KRASG12C-mutant non-small cell lung cancer (NSCLC). Broad-spectrum reversible RASGTP with or without concurrent covalent targeting yielded superior differentiated across diverse...