Lipotecan (TLC388)

The infiltration of cytotoxic T and NK cells were more profoundly existed within tumors in combination with radiotherapy and ICIs, leading to superior therapeutic efficacy in poorly immunogenic MSS-CRC. Taken together, these results showed that the novel topoisomerase I inhibitor TLC388 increased cancer immunogenicity by ssDNA/STING-mediated IFN-I production, enhancing antitumor immunity for better therapeutic efficacy in combination with radiotherapy and ICIs for poorly immunogenic cancer.

Orthotopic xenografts were treated with Lipotecan and/or RT...TOP1i reinforces NK cell-activated anti-HCC effect of RT through RNF144A mediated DNA-PKcs ubiquitination. RNF144A provides a reason for differentiating radiosensitization effect between HCC cells.

Lipotecan thereby increases cancer immunogenicity and triggers an antitumor immune response to attract immune cell infiltration within the tumor microenvironment (TME) in vitro and in vivo. Taken together, these results show that lipotecan can remodel the tumor microenvironment to provoke anticancer immune responses, which can provide potential clinical benefits to the therapeutic efficacy of neoCRT in LARC patients.

TLC388, a camptothecin-derivative targeting topoisomerase I, is a potential anticancer drug. TLC388 inhibits NSCLC cell growth by inflicting DNA damage and activating G2/M checkpoint proteins that trigger G2 phase cell cycle arrest to enable DNA repair. CHIR124 enhanced the cytotoxic effect of TLC388 and induced apoptosis.

Poorly differentiated neuroendocrine carcinomas (NECs) are rare and aggressive. Currently, effective therapeutic options for treating metastatic poorly differentiated NECs beyond platinum-based chemotherapy remain elusive. In this single-arm, multicenter, phase II study, 23 patients with NEC were enrolled and received TLC388 (Lipotecan) Hydrochloride, which is a novel camptothecin analog. The results demonstrated the disease control rate of 15%, the median progression-free survival of 1.8 (95% confidence interval [CI], 0.4-15) months, and the median overall survival of 4.3 (95% CI, 1.7-15) months. Most importantly, several novel genetic mutations and pathways were identified. These results offer the opportunity to develop future treatment strategies in this rare cancer.