irinotecan

P2, N=240, Completed, SWOG Cancer Research Network | Active, not recruiting --> Completed | Trial completion date: Nov 2025 --> Jul 2025

P3, N=358, Active, not recruiting, Alliance for Clinical Trials in Oncology | Trial primary completion date: Jan 2027 --> Dec 2028

P2, N=0, Withdrawn, Hoffmann-La Roche | N=164 --> 0 | Not yet recruiting --> Withdrawn

Fatty acid synthase (FASN), the rate limiting enzyme of de novo lipogenesis, is an important regulator of CRC progression, but the FASN inhibitor TVB-2640 showed only modest efficacy in reducing tumor burden in pre-clinical studies, suggesting combination strategies might be required to prolong patient survival. Importantly, combining FASN inhibition with the chemotherapeutic drug irinotecan synergistically decreased xenograft tumor growth and delayed tumor relapse, which was potentiated by the PARP inhibitor olaparib as maintenance treatment. Taken together, this study describes a therapeutic strategy in which FASN inhibitors can be utilized to delay tumor recurrence after chemotherapy, which is a major challenge in patients with CRC.

To the best of our knowledge, this is the first reported case of cecal NEC achieving pathological complete regression with a colorectal cancer-based chemotherapy regimen. Our findings indicate that colorectal NEC may respond not only to platinum-based regimens but also to colorectal cancer-based regimens. Furthermore, CEA levels may serve as a clinically relevant biomarker to guide chemotherapy selection in this setting.

Molecular docking simulations demonstrated that the interation energy between CES2 and icaritin was significantly higher than that with cisplatin (a reported CES2 activator), which might suggest that CES2 has a higher affinity for icaritin than cisplatin. These findings have important clinical significance for reducing chemotherapy drug resistance in cancer patients. Abbreviations: CES2, Carboxylesterase 2; CRC, Colorectal cancer; CPT-11, Irinotecan; CYP3A, Cytochrome P450 3A; NR, Nuclear receptor; P53, Tumor protein p53; PPAR-α, Peroxisome proliferator-activated receptor α; PXR, Pregnane X receptor; SN-38, 7-Ethyl-10-hydroxycamptothecin; UGT1A1, UDP-glucuronosyltransferase 1A1.

Targeting SERPINA3 with antisense oligonucleotides successfully sensitized liver cancer cells to irinotecan therapy. These findings elucidate a critical mechanism of chemoresistance in liver cancer and propose targeting SERPINA3 as a promising therapeutic strategy to enhance chemotherapy efficacy.

P2, N=120, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

P1/2, N=99, Not yet recruiting, Luye Pharma Group Ltd.

P1/2, N=35, Recruiting, Roswell Park Cancer Institute | Not yet recruiting --> Recruiting

P1, N=43, Completed, University Hospital, Grenoble | Active, not recruiting --> Completed

P2, N=583, Recruiting, Chinese PLA General Hospital