Ovarian Cancer Susceptibility and Chemosensitivity to KRAS Modulation

Authors

Alexandra Maria Psaras, Binghamton University–SUNY
Steven J. McKay, Binghamton University–SUNY
Janelle Vasquez Vilela, Binghamton University–SUNY
Eddison Ospina Sanchez, Binghamton University–SUNY
Marina G. Cintrón, Binghamton University--SUNY
Kayla K. Elder, Binghamton University--SUNY
Tracy A. Brooks, Binghamton University--SUNY

Document Type

Article

Publication Date

2-5-2026

Keywords

KRAS, ovarian cancer, chemosensitization, paclitaxel, cisplatin, 3D spheroids, drug resistance, combination therapy

Abstract

KRAS is frequently amplified or overexpressed in ovarian cancer and represents a potential therapeutic target for overcoming chemoresistance. We employed complementary approaches—CRISPR/Cas9 gene editing, Tet-ON inducible knockdown, polypurine reverse Hoogsteen hairpin (PPRH) oligonucleotides, and the pan-KRAS inhibitor BI2865—to investigate whether KRAS modulation enhances chemotherapeutic efficacy in ovarian cancer models. CRISPR-mediated KRAS knockdown in SKOV-3 cells dramatically altered three-dimensional spheroid morphology, reducing the average area six-fold, and significantly enhanced sensitivity to both cisplatin and paclitaxel in 3D cultures, where paclitaxel resistance was completely reversed. The Tet-ON system demonstrated dose-dependent chemosensitization with optimal effects at intermediate KRAS knockdown levels (~50–60%). PPRH oligonucleotides at sub-cytotoxic concentrations (50 nM) reduced cisplatin and paclitaxel IC50 values by approximately 50% in 2D cultures. Pharmacological KRAS inhibition with BI2865 produced striking synergy with paclitaxel (several hundred-fold sensitizations in 2D; complete reversal of 3D resistance), and additive effects with cisplatin. In KRAS-amplified Kuramochi cells (representing high-grade serous ovarian carcinoma), BI2865 enhanced paclitaxel efficacy, despite greater baseline chemoresistance. These findings establish KRAS as a promising chemosensitization target in ovarian cancer, with particular potential for taxane-based combination therapies.

Comments

https://doi.org/10.3390/ijms27031571

Publisher Attribution

Copyright: © 2026 by the authors.Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license.

Recommended Citation

Psaras, Alexandra Maria; McKay, Steven J.; Vilela, Janelle Vasquez; Sanchez, Eddison Ospina; Cintrón, Marina G.; Elder, Kayla K.; and Brooks, Tracy A., "Ovarian Cancer Susceptibility and Chemosensitivity to KRAS Modulation" (2026). Pharmacy Faculty Scholarship. 105.
https://orb.binghamton.edu/pharmacy_fac/105

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.