Multi-Omics-Driven Advances in Targeted and Immunologic Therapies for Triple-Negative Breast Cancer

Kimiya Ganjooi, Sophia Strukel, Emma Eddy, Ryan Au, Vikrant Rai^*
Department of Translational Research, College of Osteopathic Medicine of the Pacific, Western University of Health Sciences, Pomona, CA, USA
* Corresponding Author: Vikrant Rai. Email: email
(This article belongs to the Special Issue: Novel Targeted Therapy in Oncology)

BIOCELL https://doi.org/10.32604/biocell.2026.077955

Received 20 December 2025; Accepted 26 March 2026; Published online 01 July 2026

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Abstract

Triple-negative breast cancer (TNBC) is defined by the absence of estrogen, progesterone, and human epidermal growth factor receptor 2 expression and exhibits significant molecular heterogeneity and aggressive clinical behavior. The main treatment remains traditional chemotherapy, despite the modest duration of its effects, which has intensified the search for novel, non-chemotherapeutic drugs. Over the past few years, various molecularly targeted and immune-based treatments targeting TNBC’s diverse oncogenic drivers have been uncovered. In immunotherapy, checkpoint blockade and chimeric antigen receptor (CAR)-T cells show growing promise, enabling selective tumor targeting with reduced off-target toxicity. Multi-omics investigations integrating genomic, transcriptomic, proteomic, and metabolomic information have further delineated TNBC subclassification and revealed actionable metabolic vulnerabilities, particularly in lipid metabolism. Such discoveries are now informing rational drug-combination strategies and patient stratification methods. Current trials have established immature, but promising data on PI3K inhibitors. The Lotus (ORR 40% vs. 32% in placebo), IPATunity130 (ORR 39% vs. 35% in placebo), FAIRLINE neoadjuvant (ORR 39% vs. 9%), and PAKT (ORR 34.8% vs. 28.8%) trials evaluated the overall response rate (ORR) of specific P13K inhibitors vs. placebo. By dissecting the intense molecular, spatial, and functional heterogeneity of TNBC, these platforms identify actionable, subtype-specific therapeutic targets and predict patient responses to treatment, overcoming the limitations of current, less-effective therapies.