From heterogeneity to hope: emerging markers in triple-negative breast cancer research

Abstract

Purpose of review Triple-negative breast cancer (TNBC) is a molecular subtype of breast cancer characterized by the absence of estrogen, progesterone, and HER2 receptor expression. It accounts for approximately 10-20% of all breast cancer cases and is associated with an aggressive clinical course, a high risk of early recurrence, and limited therapeutic options. Although about 40-50% of patients achieve a complete pathological response to neoadjuvant chemotherapy, the remainder develop chemoresistant tumors with an unfavorable prognosis. This underscores the need to identify novel molecular markers with prognostic and predictive value for individualized therapy. Recent findings This review provides an analysis of the available literature to identify promising molecular markers in TNBC-IDO1 (indoleamine 2,3-dioxygenase 1), DCLK1 (doublecortin-like kinase 1), and FOXC1 (forkhead box C1). These markers were selected based on their proven roles in tumor pathogenesis: IDO1 regulates tryptophan metabolism and suppresses the immune response, DCLK1 supports tumor plasticity and invasive potential, and FOXC1 promotes the aggressive basal-like phenotype and epithelial-mesenchymal transition. The review is based on a search of original research articles and systematic reviews in National Library of Medicine, PubMed, Scopus, and Web of Science from 2010 to 2024 using systematic search strategies and strict inclusion criteria. It discusses the molecular structure, mechanisms of action and expression of these markers, their interactions with the tumor microenvironment, prognostic value, and potential as predictive markers of therapy response. Special attention is paid to their roles in drug resistance, immune microenvironment formation, and potential as targets for novel therapies (e.g., DCLK1 inhibitors). Summary This systematic analysis of the literature indicates that IDO1, DCLK1, and FOXC1 are promising molecular markers for prognosis, risk stratification of recurrence, individualized treatment strategies, and identification of new therapeutic targets in TNBC. However, further research, including standardized evaluation methods, larger cohort studies, and additional clinical trials, is essential for their successful clinical implementation.

Keywords: Chemotherapy resistance; DCLK1; FOXC1; IDO1; Predictive markers; Prognosis; Triple-negative breast cancer (TNBC).