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    GENE:

    FANCL (FA Complementation Group L)

    i
    Other names: FA Complementation Group L, Fanconi Anemia-Associated Polypeptide Of 43 KDa, RING-Type E3 Ubiquitin Transferase FANCL, Fanconi Anemia Complementation Group L, E3 Ubiquitin-Protein Ligase FANCL, Fanconi Anemia Group L Protein, PHD Finger Protein 9, FAAP43, PHF9
    22d
    NCI-2017-02296: Testing Olaparib in Patients With Advanced or Metastatic (Cancer That Has Spread) Bladder Cancer and Other Genitourinary Tumors With DNA-Repair Genetic Changes (clinicaltrials.gov)
    P2, N=60, Recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Dec 2026 | Trial primary completion date: Dec 2025 --> Dec 2026
    Trial completion date • Trial primary completion date • Tumor mutational burden
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    TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ABL1 (ABL proto-oncogene 1) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • POLE (DNA Polymerase Epsilon) • CCND1 (Cyclin D1) • BAP1 (BRCA1 Associated Protein 1) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • BRD4 (Bromodomain Containing 4) • DOT1L (DOT1 Like Histone Lysine Methyltransferase) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • IKBKE (Inhibitor Of Nuclear Factor Kappa B Kinase Subunit Epsilon) • FANCC (FA Complementation Group C)
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    PALB2 mutation • BRIP1 mutation
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    FoundationOne® CDx • FoundationOne® Liquid CDx
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    Lynparza (olaparib)
    30d
    Betulinic Acid Suppresses UBE2T Expression via MAPK/ERK Inhibition to Block FANCI and FANCD2 Monoubiquitination in Glioblastoma. (PubMed, J Cell Mol Med)
    Mechanistically, BA inhibited MAPK/ERK signalling, and pharmacological reactivation of ERK reversed BA-induced suppression of UBE2T and tumour growth. Collectively, these findings uncover a previously unrecognised MAPK/ERK-UBE2T-FA axis in glioma and highlight BA as a potential adjuvant to overcome cisplatin resistance through transcriptional repression of UBE2T.
    Journal • BRCA Biomarker
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    BRCA1 (Breast cancer 1, early onset) • ERCC1 (Excision repair cross-complementation group 1) • FANCL (FA Complementation Group L) • FANCI (FA Complementation Group I) • FANCD2 (FA Complementation Group D2)
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    cisplatin
    1m
    Ginsenoside Rh2 Suppresses the Fanconi Anemia Pathway by Inhibiting NF-κB-Mediated FANCL Transcription in Bladder Cancer. (PubMed, Dose Response)
    Ginsenoside Rh2 suppresses NF-κB signaling to transcriptionally downregulate FANCL, thereby impairing FA pathway-mediated DNA repair and enhancing cisplatin cytotoxicity in bladder cancer. These findings highlight Rh2 as a potential combinatorial agent to overcome platinum resistance.
    Journal
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    FANCL (FA Complementation Group L) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    cisplatin
    2ms
    Piperine Targets the FANCL/UBE2T Complex to Inhibit the FA Pathway and Sensitize Bladder Cancer to Cisplatin. (PubMed, Dose Response)
    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.
    Journal
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    FANCL (FA Complementation Group L) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • PCNA (Proliferating cell nuclear antigen) • FANCD2 (FA Complementation Group D2) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit) • USP1 (Ubiquitin Specific Peptidase 1)
    |
    cisplatin
    5ms
    Niraparib Before Surgery in Treating Patients With High Risk Localized Prostate Cancer and DNA Damage Response Defects (clinicaltrials.gov)
    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
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • CHEK1 (Checkpoint kinase 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2) • GEN1 (GEN1 Holliday junction 5' flap endonuclease)
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    Zejula (niraparib)
    5ms
    Potential role of Fanconi anemia pathway in the pathogenesis of endometrial cancer (Review). (PubMed, Mol Med Rep)
    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.
    Review • Journal • BRCA Biomarker
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    TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PALB2 (Partner and localizer of BRCA2) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • XRCC2 (X-Ray Repair Cross Complementing 2) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • FANCI (FA Complementation Group I) • FANCM (FA Complementation Group M) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
    |
    TP53 mutation
    6ms
    Enhanced sensitivity, robust p21 activation, and sustained DNA repair responses to interstrand crosslinks in elephant cells compared to humans. (PubMed, Front Vet Sci)
    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.
    Journal
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    RAD51 (RAD51 Homolog A) • FANCL (FA Complementation Group L) • FANCD2 (FA Complementation Group D2)
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    doxorubicin hydrochloride • mitomycin • bleomycin
    7ms
    Pembrolizumab, Olaparib, Recurrent/Advanced Gastric and Gastro-esophageal Junction(GEJ) Cancer (clinicaltrials.gov)
    P1/2, N=71, Recruiting, Yonsei University | Trial completion date: May 2025 --> May 2026 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date • Checkpoint inhibition
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    HER-2 (Human epidermal growth factor receptor 2) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    HER-2 positive • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • paclitaxel
    8ms
    Olaparib in Men With High-Risk Biochemically-Recurrent Prostate Cancer Following Radical Prostatectomy, With Integrated Biomarker Analysis (clinicaltrials.gov)
    P2, N=51, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: May 2025 --> May 2026
    Trial completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation
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    Lynparza (olaparib)
    8ms
    Phase II Trial of the PARP Inhibitor Niraparib and PD-1 Inhibitor Dostarlimab in Patients With Advanced Cancers With Active Progressing Brain Metastases (STARLET) (clinicaltrials.gov)
    P2, N=120, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Aug 2027 --> Feb 2026 | Trial primary completion date: Aug 2025 --> Feb 2026
    Trial completion date • Trial primary completion date
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    PD-L1 (Programmed death ligand 1) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • RAD52 (RAD52 Homolog DNA Repair Protein)
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    PD-L1 expression
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    Zejula (niraparib) • Jemperli (dostarlimab-gxly)
    8ms
    Genomic landscape and homologous recombination repair deficiency signature in stage I-III and de novo stage IV primary breast cancers. (PubMed, Oncologist)
    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.
    Journal • BRCA Biomarker • PARP Biomarker
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    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • HRD (Homologous Recombination Deficiency) • PALB2 (Partner and localizer of BRCA2) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L)
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    HER-2 negative • PIK3CA mutation • HRD • PALB2 mutation • RAD51C mutation • RAD51D mutation
    10ms
    Talazoparib in Advanced Breast Cancer Patients With Homologous Recombinant Deficiency (clinicaltrials.gov)
    P2, N=70, Recruiting, Seoul National University Hospital | Trial completion date: May 2025 --> May 2027 | Trial primary completion date: May 2023 --> May 2027
    Trial completion date • Trial primary completion date
    |
    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51 (RAD51 Homolog A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha)
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    HRD
    |
    Talzenna (talazoparib)