Rebecca S. Heist
A5064382279- Lung Cancer Treatments and Mutations
- Lung Cancer Research Studies
- Colorectal Cancer Treatments and Studies
- Cancer therapeutics and mechanisms
- Cancer Genomics and Diagnostics
- Lung Cancer Diagnosis and Treatment
- Cancer Mechanisms and Therapy
- HER2/EGFR in Cancer Research
- Chronic Lymphocytic Leukemia Research
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Esophageal Cancer Research and Treatment
- Peptidase Inhibition and Analysis
- Gastric Cancer Management and Outcomes
- PI3K/AKT/mTOR signaling in cancer
- Melanoma and MAPK Pathways
- RNA modifications and cancer
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Liver physiology and pathology
- Hepatocellular Carcinoma Treatment and Prognosis
- Pancreatic and Hepatic Oncology Research
- Advanced Breast Cancer Therapies
- Cancer-related Molecular Pathways
- Cancer-related molecular mechanisms research
- Synthesis and biological activity
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Boston University
2008-2020
Dana-Farber Cancer Institute
2007-2019
VA Boston Healthcare System
2019
Translational Genomics Research Institute
2018
HonorHealth
2018
Mary Crowley Cancer Research Center
2018
University of Colorado Anschutz Medical Campus
2018
Sarah Cannon
2012-2018
Lung cancers undergo dynamic genetic and histological changes upon developing resistance to EGFR inhibitors.
The EML4-ALK fusion oncogene represents a novel molecular target in small subset of non-small-cell lung cancers (NSCLC). To aid identification and treatment these patients, we examined the clinical characteristics outcomes patients who had NSCLC with without EML4-ALK.Patients were selected for genetic screening on basis two or more following characteristics: female sex, Asian ethnicity, never/light smoking history, adenocarcinoma histology. was identified by using fluorescent situ...
Purpose Programmed death 1 is an immune checkpoint that suppresses antitumor immunity. Nivolumab, a fully human immunoglobulin G4 programmed inhibitor antibody, was active and generally well tolerated in patients with advanced solid tumors treated phase I trial expansion cohorts. We report overall survival (OS), response durability, long-term safety non–small-cell lung cancer (NSCLC) receiving nivolumab this trial. Patients Methods (N = 129) heavily pretreated NSCLC received 1, 3, or 10...
Advanced, anaplastic lymphoma kinase (ALK)-positive lung cancer is currently treated with the first-generation ALK inhibitor crizotinib followed by more potent, second-generation inhibitors (e.g., ceritinib and alectinib) upon progression. Second-generation are generally effective even in absence of crizotinib-resistant mutations, likely reflecting incomplete inhibition many cases. Herein, we analyzed 103 repeat biopsies from ALK-positive patients progressing on various inhibitors. We find...
Among patients with non–small-cell lung cancer (NSCLC), MET exon 14 skipping mutations occur in 3 to 4% and amplifications 1 6%. Capmatinib, a selective inhibitor of the receptor, has shown activity models various types activation.
Purpose In two phase III studies, nivolumab, a programmed death-1 (PD-1) inhibitor antibody, improved overall survival (OS) versus docetaxel in pretreated advanced non–small-cell lung cancer (NSCLC). We report 5-year follow-up results from an early I study of nivolumab this patient population and describe characteristics survivors. Patients Methods with pretreated, NSCLC received 1, 3, or 10 mg/kg every 2 weeks 8-week cycles for up to 96 weeks. OS the time first dose was estimated by...
Non-small-cell lung cancer (NSCLC) with a mutation in the gene encoding epidermal growth factor receptor (EGFR) is sensitive to approved EGFR inhibitors, but resistance develops, mediated by T790M most cases. Rociletinib (CO-1686) an inhibitor active preclinical models of EGFR-mutated NSCLC or without T790M.In this phase 1-2 study, we administered rociletinib patients who had disease progression during previous treatment existing inhibitor. In expansion (phase 2) part T790M-positive received...
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.
Prior research shows that introducing palliative care soon after diagnosis for patients with metastatic non-small-cell lung cancer (NSCLC) is associated improvements in quality of life, mood, and survival. We sought to investigate whether early also affects the frequency timing chemotherapy use hospice these patients.This secondary analysis based on a randomized controlled trial 151 newly diagnosed NSCLC presenting an outpatient clinic at tertiary center from June 2006 July 2009....
Clinical trials of the KRAS inhibitors adagrasib and sotorasib have shown promising activity in cancers harboring glycine-to-cysteine amino acid substitutions at codon 12 (KRAS
We present a cohort of 41 patients with osimertinib resistance biopsies, including 2 an acquired CCDC6-RET fusion. Although RET fusions have been identified in resistant EGFR-mutant non-small cell lung cancer (NSCLC), their role to EGFR inhibitors is not well described. To assess the biological implications cancer, we expressed PC9 (EGFR del19) and MGH134 L858R/T790M) cells found that was sufficient confer tyrosine kinase (TKI). The selective BLU-667 cabozantinib resensitized...
Abstract Mutant-selective KRASG12C inhibitors, such as MRTX849 (adagrasib) and AMG 510 (sotorasib), have demonstrated efficacy in KRASG12C-mutant cancers, including non–small cell lung cancer (NSCLC). However, mechanisms underlying clinical acquired resistance to inhibitors remain undetermined. To begin define the mechanistic spectrum of resistance, we describe a patient with NSCLC who developed polyclonal emergence 10 heterogeneous alterations serial cell-free DNA spanning four genes (KRAS,...
Abstract Adenosine mediates immunosuppression within the tumor microenvironment through triggering adenosine 2A receptors (A2AR) on immune cells. To determine whether this pathway could be targeted as an immunotherapy, we performed a phase I clinical trial with small-molecule A2AR antagonist. We find that molecule can safely block signaling in vivo. In cohort of 68 patients renal cell cancer (RCC), also observe responses alone and combination anti–PD-L1 antibody, including subjects who had...
Abstract The cornerstone of treatment for advanced ALK-positive lung cancer is sequential therapy with increasingly potent and selective ALK inhibitors. third-generation inhibitor lorlatinib has demonstrated clinical activity in patients who failed previous To define the spectrum mutations that confer resistance, we performed accelerated mutagenesis screening Ba/F3 cells expressing EML4–ALK. Under comparable conditions, N-ethyl-N-nitrosourea (ENU) generated numerous crizotinib-resistant but...
The NCCN Guidelines for Small Cell Lung Cancer (SCLC) address all aspects of disease management. These Insights focus on recent updates to the SCLC regarding immunotherapy, systemic therapy, and radiation therapy. For 2018 update, new sections were added “Signs Symptoms SCLC” “Principles Pathologic Review.”
In a randomized trial, early palliative care (EPC) in patients with metastatic non-small-cell lung cancer (NSCLC) was observed to improve survival. secondary analysis, we explored the hypothesis that survival benefit resulted from improving depression.In total, 151 newly diagnosed NSCLC participated trial of EPC integrated standard oncology versus alone. Depression assessed at baseline and 12 weeks Patient Health Questionnaire-9 (PHQ-9) scored diagnostically by using Diagnostic Statistical...
Abstract Small-cell lung cancer (SCLC) is an aggressive malignancy in which inhibitors of PARP have modest single-agent activity. We performed a phase I/II trial combination olaparib tablets and temozolomide (OT) patients with previously treated SCLC. established recommended II dose 200 mg orally twice daily 75 mg/m2 daily, both on days 1 to 7 21-day cycle, expanded total 50 patients. The confirmed overall response rate was 41.7% (20/48 evaluable); median progression-free survival 4.2 months...
Small cell lung cancer (SCLC) patient-derived xenografts (PDX) can be generated from biopsies or circulating tumor cells (CTC), though scarcity of tissue and low efficiency growth have previously limited these approaches. Applying an established clinical-translational pipeline for collection automated microfluidic platform CTC enrichment, we 17 biopsy-derived PDXs CTC-derived in a 2-year timeframe, at 89% 38% efficiency, respectively. Whole-exome sequencing showed that somatic alterations...
Purpose Given the pivotal role of epidermal growth factor receptor (EGFR) inhibitors in advanced EGFR-mutant non–small-cell lung cancer (NSCLC), we tested adjuvant erlotinib patients with early-stage NSCLC. Materials and Methods In this open-label phase II trial, resected stage IA to IIIA (7 th edition American Joint Committee on Cancer staging system) NSCLC were treated 150 mg per day for 2 years after standard chemotherapy or without radiotherapy. The study was designed 100 powered...
Cancer-associated fibroblasts (CAFs) are highly heterogeneous. With the lack of a comprehensive understanding CAFs' functional distinctions, it remains unclear how cancer treatments could be personalized based on CAFs in patient's tumor. We have established living biobank derived from biopsies patients' non-small lung (NSCLC) that encompasses broad molecular spectrum clinical NSCLC. By functionally interrogating CAF heterogeneity using same therapeutics received by patients, we identify...
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...
Abstract Purpose: Patients with KRAS-mutant non–small cell lung cancer (NSCLC) brain metastases (BM) have a poor prognosis. Adagrasib (MRTX849), potent oral small-molecule KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state. has been optimized for favorable pharmacokinetic properties, including long half-life (∼24 hours), extensive tissue distribution, dose-dependent pharmacokinetics, central nervous system penetration; however, BM-specific...