Indole hybrids as promising anti-hepatocellular carcinoma agents: a comprehensive review of recent advances and therapeutic prospects

Hepatocellular carcinoma (HCC), the primary type of liver cancer, ranks among the leading causes of cancer-related deaths globally due to its high incidence and poor prognosis. Moreover, the high recurrence rate and acquired resistance to existing therapies further exacerbate the therapeutic challenges of HCC, underscoring the urgent need for novel and potent anti-HCC agents. Indole hybrids exhibit prominent advantages in HCC treatment by acting on multiple targets implicated in tumor progression, a feature that enables more comprehensive anticancer effects than single-target agents. Besides, indole hybrids may help mitigate drug resistance to conventional therapies, addressing a major clinical challenge. Their preliminary favorable safety performance, with minimal damage to normal liver tissues, warrants further investigation for therapeutic application. Moreover, preclinical studies have demonstrated their ability to inhibit HCC growth and metastasis, supporting their promise as novel candidates for HCC therapy. This review summarizes the current landscape of indole hybrids developed from 2021 to the present that exhibit anti-HCC potential, aiming to open new avenues for the discovery of novel anti-HCC candidates.