Therapeutic vulnerabilities in triple negative breast cancer: Stem-like traits explored within molecular classification

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence. However, heterogeneity within TNBC often generally restricts the stability of the therapeutic efficacy. To understand the heterogeneity and manage TNBC more precisely, multiple TNBC subtyping categories have been reported, providing the basis for profile-according therapeutic regimens. To provide more insight into targeting stem-like traits to ablate TNBC and reduce recurrence in the context of heterogeneity, this paper reviewed the molecular subtyping of TNBC, identified the consensus subtypes with distinct stem-like phenotypes, characterized the stemness hierarchy of TNBC, outlined the biological models for stem-like TNBC subtypes, summarized the therapeutic vulnerabilities in stem-like traits of the subtypes, and proposed potential therapeutic regimens targeting stem-like characteristics to improve TNBC prognosis.