Indole hybrids: Emerging therapeutic candidates for breast cancer (2023-2025)

Breast cancer inflicts severe multidimensional harm on physical health, mental well-being, and quality of life, with its impacts spanning localized tissue damage, systemic complications, and long-term functional impairment. Breast cancer remains the most frequently diagnosed cancer and the second leading cause of cancer-related mortality among women worldwide, with its epidemiological burden exhibiting substantial regional variation. Current chemotherapy drugs for breast cancer face critical dilemmas, including widespread primary and secondary drug resistance, as well as severe side effects that harm quality of life and compliance. Additionally, these drugs show limited curative effects in advanced breast cancer, where achieving a cure remains difficult and treatment primarily focuses on controlling tumor progression and extending survival, an area still in need of improvement for long-term outcomes. Indole hybrids have emerged as a highly promising class of therapeutic agents for breast cancer therapy, distinguished by their unique structural design that integrates an indole core with diverse pharmacophores to synergize antitumor activities, enhance subtype selectivity, and surmount key limitations of conventional treatments. Their versatility enables targeted intervention across multiple breast cancer subtypes by modulating critical oncogenic pathways, making them a focal point in preclinical and early clinical research. The present manuscript aims to summarize the current landscape of indole hybrids with therapeutic potential against breast cancers and address their structure-activity relationships and mechanisms of action, covering literature published since 2023, to inform the further rational design of novel candidates.