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TOP1 Mutations and Cross-Resistance to Antibody-Drug Conjugates in Patients with Metastatic Breast Cancer.
Clin Cancer Res
January 2025
University of California, Los Angeles, Los Angeles, CA, United States.
Purpose: Antibody-drug conjugates (ADCs) harboring topoisomerase I (TOP1) inhibitor payloads have improved survival for patients with metastatic breast cancer (MBC). However, knowledge of ADC resistance mechanisms and potential impact on sequential use of ADCs is limited. Here, we report the incidence and characterization of TOP1 mutations arising in the setting of ADC resistance in MBC.
View Article and Find Full Text PDFEvolutionary rescue model informs strategies for driving cancer cell populations to extinction.
bioRxiv
January 2025
Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
Cancers exhibit a remarkable ability to develop resistance to a range of treatments, often resulting in relapse following first-line therapies and significantly worse outcomes for subsequent treatments. While our understanding of the mechanisms and dynamics of the emergence of resistance during cancer therapy continues to advance, questions remain about how to minimize the probability that resistance will evolve, thereby improving long-term patient outcomes. Here, we present an evolutionary simulation model of a clonal population of cells that can acquire resistance mutations to one or more treatments.
View Article and Find Full Text PDFEvolution of Rapid Clonal Dynamics and Non-Cross-Resistance in Response to Alternating Targeted Therapy and Chemotherapy in BRAF-V600E-Mutant Colon Cancer.
JCO Precis Oncol
December 2024
Department of Medicine, Rutgers Cancer Institute of New Jersey, Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ.
Purpose: Combined BRAF, MEK, and EGFR inhibition can induce clinical responses in BRAF-V600E-mutant colon cancer, but rapid resistance often occurs.
Methods: We use serial monitoring of circulating tumor DNA cell-free plasma DNA (cfDNA) in a patient case study in addition to organoids derived from mouse models of BRAF-V600E-mutant intestinal cancer, which emulated the patient's mutational profile to assess drug treatment efficacy.
Results: We demonstrate dynamic evolution of resistance to combined EGFR/BRAF/MEK inhibition in a pediatric patient with metastatic BRAF-V600E-mutant, mismatch repair-stable colon cancer.
Phenotypic and Genotypic Responses of Foodborne Pathogens to Sublethal Concentrations of Lactic Acid and Sodium Chloride.
Microb Drug Resist
August 2024
Department of Biomedical Science, Kangwon National University, Chuncheon, Republic of Korea.
The aim of this study was to evaluate the phenotypic and genotypic responses of Typhimurium ATCC 19585 (ST) and KACC 13236 (SA) preadapted to sublethal concentrations of lactic acid (LA) and sodium chloride (NaCl) for 48 hr at 37°C, followed by re-exposure to lethal concentrations of LA and NaCl for 24 hr at 37°C. ST and SA treated in a sequential and ordered manner with LA and NaCl were assigned as LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl. The treatments, LA-LA, LA-NaCl, NaCl-LA, and NaCl-NaCl, were evaluated by antimicrobial susceptibility, bacterial fluctuation, relative fitness, zeta potential, and gene expression.
View Article and Find Full Text PDFOptimal Sequential Strategies for Antibody-Drug Conjugate in Metastatic Breast Cancer: Evaluating Efficacy and Cross-Resistance.
Oncologist
August 2024
Department of Medical Oncology, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China.
Background: The optimal sequential strategy for antibody-drug conjugates (ADCs) in breast cancer remains uncertain. This study aimed to evaluate the efficacy and potential resistance of second ADC (ADC2) following the first ADC (ADC1) in human epidermal growth factor receptor 2 (HER2)-positive and HER2-low MBC.
Methods: This retrospective, multicenter, real-world study enrolled patients with MBC who received at least 2 different types of ADCs in 3 hospitals in China between July 1, 2017 and May 1, 2023.
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