Louisiana Via Research Day Book 2026

Biomedical Research: Section 1

Biomedical Research: Section 1

Hana Khalifa, OMS-II; Alessandra, Martinez, OMS-II; Kasia Michalak, MSc; Zakaria Abd Elmageed, PhD; Hassan Ebrahim, PhD VCOM-Louisiana 7 THE NATURAL DITERPENE CAFESTOL ATTENUATES THE PROLIFERATION, MIGRATION, COLONIZATION OF BREAST CANCER CELLS THROUGH MODULATING MTOR

David Solis, OMS-III; Dinesh Aryal, PhD VCOM-Louisiana 8 IMPACT OF GATA3, PIK3CA, AND TP53 MUTATIONS ON ENDOCRINE THERAPY RESPONSE (TAMOXIFEN VS FULVESTRANT VS LETROZOLE) IN HR+ INVASIVE DUTAL BREAST CARCINOMA USING MSK-CHORD CBIOPORTAL DATA

Context: Green coffee has been studied for its potential health benefits, particularly its role in cancer treatment and prevention. It harbor a diverse range of bioactive ingredients including fatty acids, terpenes and phenolics. Cafestol is a diterpene compound (C20) found in unroasted coffee beans, and it has gained attention due to its potential health effects, including anti-inflammatory and antioxidant effects. Breast cancer (BC) is the most diagnosed cancer in women and the second leading cause of cancer death, behind lung cancer. BC is a highly heterogenous disease, characterized by a wide range of subtypes that vary in their biological features, clinical presentation, and response to treatment. mTOR (mechanistic target of rapamycin) is a key regulator of many cellular processes, including growth, proliferation, metabolism, and survival. It’s a part of the complex mTOR signaling pathway, which integrates signals from growth factors, nutrients, energy status, and cellular stress. mTOR plays a crucial role in regulating the growth of breast cancer cells, and its dysregulation can contribute to cancer progression, metastasis, and resistance to treatment.

Objective and/or Hypothesis: As a part of an ongoing project to discover novel anticancer molecules of natural origin, we explored anticancer effects of cafestol against breast cancer cells of different phenotypic characteristics. Methods: MTT assay was conducted to evaluate the growth of BC cells, while wound healing assay was used to monitor cell migration. Western blot was used to uncover the potential molecular target mediating the anticancer effect of cafestol. Results: Bioassay-guided fractionation of coffee beans extract lead to the identification of cafestol as potential anticancer diterpene against multiple breast cancer cells. Cafestol effectively attenuated the growth, migration, and colonization of BC cells at low µM concentrations. Furthermore, cafestol significantly inhibited mTOR kinase in a dose-dependent manner, as demonstrated by Western blot. Furthermore, molecular modeling studies suggested a potential low-energy binding conformation of cafestol at the mTOR kinase pocket, stabilized by

interactions with key amino acids at C-terminal lobe of the kinase domain.

Background: Impact of PIK3CA, TP53, and GATA3 Mutations on Endocrine Therapy Response in Hormone Receptor–Positive Invasive Ductal Breast Carcinoma Background: Hormone receptor–positive (HR+) breast cancer accounts for the majority of breast cancer diagnoses and is primarily treated with endocrine therapy. Despite improved outcomes, intrinsic and acquired resistance to endocrine agents remains a major clinical challenge. Genomic alterations, particularly in PIK3CA, TP53, and GATA3, are common in HR+ disease and have been shown to influence estrogen receptor signaling and therapeutic response. However, comparative survival outcomes across different endocrine therapies stratified by mutation status remain poorly defined. Objective: To determine whether mutations in PIK3CA, TP53, or GATA3 are associated with differential overall survival outcomes among HR+ invasive ductal carcinoma patients treated with tamoxifen, letrozole, or fulvestrant.

accessed through cBioPortal. The cohort included 2,557 patients with HR+ invasive ductal breast carcinoma. Patients were stratified by mutation status (PIK3CA, TP53, GATA3) and by endocrine therapy type (tamoxifen, letrozole, or fulvestrant monotherapy). Overall survival was analyzed using Kaplan–Meier methods, with comparisons assessed by log-rank testing. Overlapping treatment cases were excluded to maintain mutually exclusive therapy groups. Statistical significance was defined as p < 0.05. Results: Across the entire cohort, mutation status significantly predicted overall survival (p = 2.37 × 10 -3 ), with TP53 mutations associated with the poorest outcomes. In the tamoxifen treated cohort, GATA3 mutations conferred the most favorable survival, while TP53 mutations were associated with inferior outcomes (p = 2.77 × 10 - ³). Among letrozole-treated patients, PIK3CA mutations were associated with the highest survival probabilities, followed by GATA3, with TP53 remaining the poorest prognostic marker (p = 3.46 × 10 -3 ). In the fulvestrant cohort, GATA3-mutant tumors demonstrated superior survival, while TP53 mutations again predicted poor outcomes (p = 1.83 × 10 -3 ).

Conclusions: Mutations in PIK3CA, TP53, and GATA3 are associated with distinct survival patterns across endocrine therapy types in HR+ breast cancer. TP53 mutations consistently predict poor outcomes, while GATA3 and PIK3CA mutations are associated with more favorable survival, with therapy-specific differences observed. These findings support the integration of genomic profiling into endocrine therapy selection to improve personalized treatment strategies in HR+ breast cancer.

Conclusions: Cafestol is a novel mTOR modulator amenable for further development as a lead compound for the control of breast malignancies.

Methods: A retrospective analysis was conducted using the MSK-CHORD dataset

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2026 Research Recognition Day