FANCL (FA Complementation Group L)

Our findings uncover piperine as a natural compound that allosterically inhibits UBE2T activity within the FA pathway, thereby impairing ID2 monoubiquitination and enhancing cisplatin sensitivity in bladder cancer. This study highlights the therapeutic potential of piperine and provides a rationale for targeting the FA repair axis to overcome platinum resistance.

P2, N=11, Active, not recruiting, Marc Dall'Era, MD | Recruiting --> Active, not recruiting | N=30 --> 11 | Trial completion date: Jun 2025 --> Dec 2025 | Trial primary completion date: Jun 2025 --> Dec 2025

This comprehensive review provides a systematic summary of EC‑related FA genes, elucidates the roles of various FA genes in EC and further speculates on their related mechanisms to facilitate the development of targeted therapies that specifically target key genes, leading to a more accurate and efficient treatment for EC. The present review searched PubMed and Google Scholar for articles published in English up to June 2025 using keywords such as Fanconi anemia pathway, 22 FA genes (FANCA, FANCB, FANCC, FANCD1/BRCA2, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ/BRIP1, FANCL, FANCM, FANCN/PALB2, FANCO/RAD51C, FANCP/SLX4, FANCQ/XPF, FANCR/RAD51, FANCS/BRCA1, FANCT/UBE2T, FANCU/XRCC2, FANCV/REV7, FANCW/RFWD3), endometrial cancer (type I: Endometrioid adenocarcinoma; Type II Uterine serous carcinoma, clear‑cell carcinoma, carcinosarcoma), somatic copy number alterations, microsatellite instability, TP53 mutations, pathogenesis, genomic instability, target therapy.

We found that elephant fibroblasts exhibited higher sensitivity to ICL-inducing treatments, such as mitomycin C and trimethylpsoralen plus UVA (PUVA), than human fibroblasts, while showing comparable or reduced sensitivity to other DNA-damaging agents, such as doxorubicin and bleomycin. These findings suggest that elephants efficiently repair ICLs in growth-arrested cells likely through robust p21 activation. This study provides new insights into the cancer resistance mechanisms of elephants and offers novel approaches for cancer prevention and therapy.

P1/2, N=71, Recruiting, Yonsei University | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025

P2, N=51, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2025 --> May 2026

P2, N=120, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2027 --> Feb 2026 | Trial primary completion date: Aug 2025 --> Feb 2026

Early-stage (I-III) and de novo stage IV breast cancers shared a similar prevalence of targetable genomic alterations and overall genomic landscape. HRDsig identified approximately 16% of breast cancers without g/sBRCA/gPALB2 alteration that might potentially benefit from PARP inhibitors or platinum-based treatments and should be tested in future clinical studies.

P2, N=70, Recruiting, Seoul National University Hospital | Trial completion date: May 2025 --> May 2027 | Trial primary completion date: May 2023 --> May 2027

This establishes FAAP100 deficiency as a cause of Fanconi anemia, with FAAP100 gaining an alias as FANCX. The extensive developmental malformations of individuals with FAAP100 loss-of-function variants are among the most severe across previously described FA phenotypes, indicating that the FA pathway is essential for human development.

Mechanistically, FAAP100T542P impairs ligase activity by preventing BLP100 subcomplex formation, resulting in defective FAAP100T542P nuclear translocation and chromatin recruitment. FAAP100 dysfunction that disrupts the FA pathway and impairs genomic maintenance, together with FAconsistent human manifestations, recommends FAAP100 as a legitimate FA gene, FANCY.

P2, N=20, Recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Mar 2026 --> Mar 2028 | Trial primary completion date: Mar 2025 --> Mar 2027