A5068764214- HER2/EGFR in Cancer Research
- Radiomics and Machine Learning in Medical Imaging
- Advanced Radiotherapy Techniques
- Monoclonal and Polyclonal Antibodies Research
- Lanthanide and Transition Metal Complexes
- Cancer Genomics and Diagnostics
- Electron Spin Resonance Studies
- PARP inhibition in cancer therapy
- Effects of Radiation Exposure
- Medical Imaging Techniques and Applications
- Cancer Treatment and Pharmacology
- Prostate Cancer Diagnosis and Treatment
- Magnetism in coordination complexes
- Genetic factors in colorectal cancer
- Ultrasound and Hyperthermia Applications
- Ocular Oncology and Treatments
- Radiopharmaceutical Chemistry and Applications
- Cancer, Hypoxia, and Metabolism
- Advanced Breast Cancer Therapies
- Biosimilars and Bioanalytical Methods
- Immunotherapy and Immune Responses
- Prostate Cancer Treatment and Research
- Radiation Dose and Imaging
- Advanced MRI Techniques and Applications
- Cancer-related Molecular Pathways
Massachusetts General Hospital
2021-2024
Harvard University
2021-2024
Center for Cancer Research
2021
CRUK/MRC Oxford Institute for Radiation Oncology
2015-2020
University of Oxford
2016-2020
Medical Research Council
2019
Cancer Research UK
2019
McGill University
2013-2019
Université Paris Cité
2019
Hôpital Européen Georges-Pompidou
2019
Sacituzumab govitecan (SG), the first antibody-drug conjugate (ADC) approved for triple-negative breast cancer, incorporates anti-TROP2 antibody hRS7 conjugated to a topoisomerase-1 (TOP1) inhibitor payload. We sought identify mechanisms of SG resistance through RNA and whole-exome sequencing pretreatment postprogression specimens. One patient exhibiting de novo progression lacked TROP2 expression, in contrast robust expression focal genomic amplification TACSTD2/TROP2 observed with deep,...
Abnormal pH is a common feature of malignant tumors and has been associated clinically with suboptimal outcomes. Amide proton transfer magnetic resonance imaging (APT MRI) holds promise as means to noninvasively measure tumor pH, yet multiple factors collectively make quantification from APT MRI data challenging. The purpose this study was improve our understanding the biophysical sources altered signals in tumors. Combining
Abstract Purpose: The antibody–drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP TOP1 inhibitors failed due dose-limiting myelosuppression. Here, we assess proof-of-mechanism clinical feasibility for SG talazoparib (TZP)...
Abstract Background: Sacituzumab Govitecan (SG), the first antibody-drug conjugate approved for metastatic TNBC (mTNBC), is comprised of SN-38 (active metabolite irinotecan), a topoisomerase I (TOP1) inhibitor, coupled via hydrolyzable linker to monoclonal antibody targeting trophoblast cell surface antigen 2 (Trop-2), an overexpressed in mTNBC. Poly (ADP-ribose) polymerase inhibitors (PARPi) block resolution TOP1 cleavage complexes (TOP1CCs) induced by inhibitors, thus unmasking inability...
Inter‐patient radiation sensitivity variability has recently been shown to have a genetic component. This component may play key role in explaining the fluctuating rates of radiation‐induced toxicities (RITs). Single nucleotide polymorphisms (SNPs) thus far yielded inconsistent results delineating RITs while copy number variations (CNVs) not yet investigated for such purposes. We explore radiogenomic modeling approach investigate association CNVs and SNPs, along with clinical dosimetric...
Abstract Platinum chemotherapies are highly effective cytotoxic agents but often induce resistance when used as monotherapies. Combinatorial strategies limit this risk and provide treatment options for many cancers. Here, we repurpose atovaquone (ATQ), a well-tolerated & FDA-approved anti-malarial agent by demonstrating that it potentiates cancer cell death of subset platinums. We show ATQ in combination with carboplatin or cisplatin induces striking repeatable concentration-...
<p>Figure S1. Schematic illustrating proposed temporal window created by SG-mediated drug delivery to enable sequential TOP1i/PARP1i dosing</p>
Abstract Antibody Drug Conjugates (ADCs) are proving to be groundbreaking therapeutics for all breast cancer subtypes. Sacituzumab govitecan (SG), an ADC targeting the TROP2 tumor antigen and harboring a topoisomerase 1 inhibitor payload, improves overall survival in advanced Hormone Receptor positive (HR+) Triple Negative Breast Cancer (TNBC). However, SG has not been tested early-stage cancer, response predictors mechanisms of resistance any setting remain defined. We thus designed NeoSTAR...
Abstract Antibody drug conjugates (ADCs) are revolutionizing precision therapeutics in oncology. Sacituzumab Govitecan (SG), combining a Topoisomerase I (TOP1) inhibitor payload (SN38) and the tumor-selective antigen TROP2-targeting antibody hRS7, has demonstrated efficacy challenging cancers including triple negative breast cancer (TNBC). Despite its promising clinical efficacy, intricacies of sensitivity resistance mechanisms to SG remain elusive. To systematically interrogate ADC...
<div>AbstractPurpose:<p>The antibody–drug conjugate (ADC) sacituzumab govitecan (SG) comprises the topoisomerase 1 (TOP1) inhibitor (TOP1i) SN-38, coupled to a monoclonal antibody targeting trophoblast cell surface antigen 2 (TROP-2). Poly(ADP-ribose) polymerase (PARP) inhibition may synergize with TOP1i and SG, but previous studies combining systemic PARP TOP1 inhibitors failed due dose-limiting myelosuppression. Here, we assess proof-of-mechanism clinical feasibility for SG...