Rama Soundararajan

Deep learning–based histologic classifiers enable molecular subtyping of metastatic prostate cancer

Zhijun Chen, Erolcan Sayar, Daniela Guevara, Helen Richards et autres

Metastatic prostate cancer is a clinically and molecularly heterogeneous disease. Under the selective pressure of androgen receptor (AR)-directed therapies, resistant phenotypes frequently emerge, posing significant diagnostic and therapeutic challenges. Neuroendocrine prostate cancer (NEPC) is a clinically important phenotype characterized by lineage plasticity, …

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Targeting arginine metabolism overcomes chemotherapy resistance in aggressive-variant prostate cancers

Elavarasan Subramani, Patrick G. Pilié, Rebecca Slack-Tidwell, Paul V. Viscuse et autres

Aggressive-variant prostate cancers (AVPCs) respond poorly to anti-androgen therapy but show sensitivity to taxane-platinum chemotherapy, though outcomes remain poor. We conducted a phase 2 trial testing induction cabazitaxel plus carboplatin (CabCarb) followed by olaparib maintenance versus observation in men with AVPC. The …

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Early chemo-induced TME alterations as a predictor of response to PD-1 blockade in AVPC: Single-cell data from C3NIRA.

Anthos Christofides, Sreyashi Basu, Zhong He, Rama Soundararajan et autres

5065 Background: Aggressive variant prostate cancer (AVPC) criteria enrich for androgen-indifferent disease that is highly aggressive and has limited therapeutic options. Single-agent immune checkpoint inhibitors have not demonstrated activity in prostate cancer patients. The C-COLA study (NCT03263650) showed that Cabazitaxel/Carboplatin (CabCarb) elicited …

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Enhancing Pathology Knowledge for Biomedical Scientists: Pilot Cohort Study of a Comprehensive Self-Paced Tutorial for Bridging Fundamental Concepts With Translational Applications

Jennifer Sells, Letícia Campos Clemente, David Farris, Mary Sizemore et autres

Background: Knowledge of pathology is integral to numerous health care and research disciplines, besides routine laboratory-medicine operations. Despite its importance, there remains a significant gap in structured educational programs designed to provide a fundamental understanding of the pathologic basis of disease for …

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EMT-induced stem cell and mesenchymal programs can be decoupled via cell division and ESRP1-dependent mechanisms

Petra den Hollander, María Castañeda, Suhas Vasaikar, Joanna Joyce Maddela et autres

Epithelial-to-mesenchymal transition (EMT) is known to induce both stemness and mesenchymal properties, and our findings reveal that these two programs can be uncoupled. During EMT, epithelial cells transition from symmetric divisions producing differentiated daughter cells to self-renewing daughter cells. When we block …

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Enhancing Pathology Knowledge for Biomedical Scientists: A Comprehensive Self-Paced Online Curriculum for Bridging Fundamental Concepts and Translational Applications (Preprint)

Jennifer Sells, Letícia Campos Clemente, David Farris, Mary Sizemore et autres

BACKGROUND Pathology is a cornerstone discipline in both clinical medicine and biomedical research, serving as a bridge between basic science discoveries and their translational applications. However, many biomedical scientists and healthcare professionals lack structured training in the fundamental principles of pathology. This …

C3NIRA: Randomized phase II study of carboplatin-cabazitaxel-cetrelimab (anti-PD-1) induction followed by niraparib +/- cetrelimab maintenance in men with aggressive variant prostate cancers (AVPC).

Ana M. Aparicio, Rebecca S. Tidwell, Sreyashi Basu, Zhong He et autres

5008 Background: AVPC have limited therapeutic options and a dismal prognosis. Although early data indicate that adding carboplatin (Carb) to cabazitaxel (Cab) benefits men with AVPC, responses are short-lived. In a previous study (NCT03263650) a subset of AVPC patients had long-term responses …

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Abstract 4122: Epigenetic biomarker identification of each stage during the progression of prostate cancer

Konstantinos Mesiakaris, Konstantinos Lazaros, Eleni Panopoulou, Stavros Kontogiannis et autres

Abstract Prostate cancer (PCa) heterogeneity is observed both across different patients and within the same patient during the progression of his disease. Although genetic profiling alone has not fully captured these complexities, epigenetic modifications may better characterize changes in bidirectional gene regulatory …

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β-Catenin Drives the FOXC2-Mediated Epithelial–Mesenchymal Transition and Acquisition of Stem Cell Properties

María Castañeda, Petra den Hollander, Steven J. Werden, Esmeralda Ramirez‐Peña et autres

Background: Aggressive forms of breast cancer, such as triple-negative breast cancer (TNBC), are associated with an increase in cancer cells that exhibit stem cell properties. The activation of the epithelial–mesenchymal transition (EMT) program, mediated by the transcription factor FOXC2, generates these stem-like …

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Supplementary Figure S8 from A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration–Resistant Prostate Cancer

Ana M. Aparicio, Rebecca S. Tidwell, Shalini S. Yadav, Jiun‐Sheng Chen et autres

Supplementary Figure S8. Heatmap showing immune-related Level 1 Reactome and selected Cancer Hallmark pathways in bulk RNA sequencing of baseline metastatic lymph node biopsies from patients allocated to the Satisfactory (n=27) and Unsatisfactory (n=13) groups.

Data from A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration–Resistant Prostate Cancer

Ana M. Aparicio, Rebecca S. Tidwell, Shalini S. Yadav, Jiun‐Sheng Chen et autres

AbstractPurpose: To determine the efficacy and safety of risk-adapted combinations of androgen signaling inhibitors and inform disease classifiers for metastatic castration–resistant prostate cancers. Patients and Methods: In a modular, randomized phase II trial, 192 men were treated with 8 weeks of abiraterone …

Supplementary Figure S8 from A Modular Trial of Androgen Signaling Inhibitor Combinations Testing a Risk-Adapted Strategy in Patients with Metastatic Castration–Resistant Prostate Cancer

Ana M. Aparicio, Rebecca S. Tidwell, Shalini S. Yadav, Jiun‐Sheng Chen et autres

Supplementary Figure S8. Heatmap showing immune-related Level 1 Reactome and selected Cancer Hallmark pathways in bulk RNA sequencing of baseline metastatic lymph node biopsies from patients allocated to the Satisfactory (n=27) and Unsatisfactory (n=13) groups.