Single-Cell Proteomic and Transcriptomic Characterization of Drug-Resistant Prostate Cancer Cells Reveals Molecular Signatures Associated with Morphological Changes.

This study delves into the proteomic intricacies of drug-resistant cells (DRCs) within prostate cancer, which are known for their pivotal roles in therapeutic resistance, relapse, and metastasis. Utilizing single-cell proteomics (SCP) with an optimized high-throughput Data Independent Acquisition (DIA) approach with the throughput of 60 sample per day, we characterized the proteomic landscape of DRCs in comparison to parental PC3 cells. This optimized DIA method allowed for robust and reproducible protein quantification at the single-cell level, enabling the identification and quantification of over 1,300 proteins per cell on average.

Targeting heterogeneous tumor microenvironments in pancreatic cancer mouse models of metastasis by TGF-β depletion.

The dual tumor-suppressive and -promoting functions of TGF-β signaling has made its targeting challenging. We examined the effects of TGF-β depletion by AVID200/BMS-986416 (TGF-β-TRAP), a TGF-β ligand trap, on the tumor microenvironment of pancreatic ductal adenocarcinoma (PDAC) murine models with different organ-specific metastasis. Our study demonstrated that TGF-β-TRAP potentiates the efficacy of anti-programmed cell death 1 (anti-PD-1) in a PDAC orthotopic murine model with liver metastasis tropism, significantly reducing liver metastases.

MOZ and Menin-MLL Complexes Are Complementary Regulators of Chromatin Association and Transcriptional Output in Gastrointestinal Stromal Tumor.

Unlabelled: Gastrointestinal stromal tumor (GIST) is commonly characterized by activating mutations in the receptor tyrosine kinase KIT. Tyrosine kinase inhibitors are the only approved therapy for GIST, and complementary treatment strategies are urgently needed. As GIST lacks oncogene amplification and relies upon an established network of transcription factors, we hypothesized that unique chromatin-modifying enzymes are essential in orchestrating the GIST epigenome.

Preclinical Modeling of Leiomyosarcoma Identifies Susceptibility to Transcriptional CDK Inhibitors through Antagonism of E2F-Driven Oncogenic Gene Expression.

Purpose: Leiomyosarcoma (LMS) is a neoplasm characterized by smooth muscle differentiation, complex copy-number alterations, tumor suppressor loss, and the absence of recurrent driver mutations. Clinical management for advanced disease relies on the use of empiric cytotoxic chemotherapy with limited activity, and novel targeted therapies supported by preclinical research on LMS biology are urgently needed. A lack of fidelity of established LMS cell lines to their mesenchymal neoplasm of origin has limited translational understanding of this disease, and few other preclinical models have been established.