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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
    7d
    Integrated Molecular Profiling Improves Subtype Classification and Reveals Inherited Susceptibility in Medulloblastoma: Insights From a Real-World Cohort. (PubMed, Cancer Med)
    Integrated genomic and transcriptomic profiling substantially improves molecular subtyping of MB and reveals inherited risk factors relevant to specific subgroups. Our findings support the implementation of combined molecular diagnostics in routine clinical management of MB and underscore their potential in guiding individualized treatment strategies.
    Retrospective data • Journal • Real-world evidence
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCL (FA Complementation Group L) • FANCC (FA Complementation Group C)
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    CDKN2A deletion
    9d
    CX-5461-04: Study of CX-5461 in Patients With Solid Tumours and BRCA1/2, PALB2 or Homologous Recombination Deficiency (HRD) Mutation (clinicaltrials.gov)
    P1, N=52, Recruiting, Senhwa Biosciences, Inc. | Trial completion date: Dec 2026 --> Mar 2027 | Trial primary completion date: Dec 2025 --> Mar 2027
    Trial completion date • Trial primary completion date
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CCNE1 (Cyclin E1) • KMT2D (Lysine Methyltransferase 2D) • CDK12 (Cyclin dependent kinase 12) • KMT2C (Lysine Methyltransferase 2C) • SLFN11 (Schlafen Family Member 11) • CHEK2 (Checkpoint kinase 2) • CREBBP (CREB binding protein) • RAD51 (RAD51 Homolog A) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD50 (RAD50 Double Strand Break Repair Protein) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCF (FA complementation group F) • FANCL (FA Complementation Group L) • RBBP8 (RB Binding Protein 8, Endonuclease) • 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) • MAD2L2 (Mitotic Arrest Deficient 2 Like 2) • CDC25C (Cell Division Cycle 25C) • FANCD2 (FA Complementation Group D2) • FANCE (FA Complementation Group E) • FANCG (FA Complementation Group G) • MUS81 (MUS81 Structure-Specific Endonuclease Subunit) • CDC25A (Cell Division Cycle 25A) • FANCB (FA Complementation Group B) • FANCC (FA Complementation Group C) • GNRP (Ras-Specific Guanine Nucleotide-Releasing Factor 1) • RAD17 (RAD17 Checkpoint Clamp Loader Component) • SLX4 (SLX4 Structure-Specific Endonuclease Subunit)
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    BRCA2 mutation • BRCA1 mutation • PALB2 mutation
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    pidnarulex (CX-5461)
    15d
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=35, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=120 --> 35
    Enrollment closed • Enrollment change
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • BRCA (Breast cancer early onset) • 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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    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
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    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    24d
    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, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended
    Trial suspension • 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)
    1m
    A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors (clinicaltrials.gov)
    P1/2, N=120, Recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2027 --> Mar 2029 | Trial primary completion date: Mar 2026 --> Mar 2028
    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) • BRCA (Breast cancer early onset) • 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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    BRCA1 mutation • ATM mutation • PALB2 mutation • CDK12 mutation • CHEK2 mutation • BRIP1 mutation • RAD51C mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • CHEK1 mutation • RAD54L mutation
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    berzosertib (M6620) • Trodelvy (sacituzumab govitecan-hziy)
    3ms
    PARPi-PANC: Niraparib as First Line Therapy With Metastatic Homologous Repair-deficient Pancreatic Cancer (clinicaltrials.gov)
    P2, N=2, Terminated, Centre Leon Berard | Withdrawn --> Terminated; Study not feasible, patient accrual rate too low.
    Trial termination
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    BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • RAD54L (DNA Repair And Recombination Protein RAD54) • FANCL (FA Complementation Group L) • PPP2R2A (Protein Phosphatase 2, Regulatory Subunit B, Alpha) • FANCD2 (FA Complementation Group D2)
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    Zejula (niraparib)
    3ms
    Pembrolizumab, Olaparib, and Temozolomide for People With Glioma (clinicaltrials.gov)
    P2, N=57, Recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jan 2026 --> Jan 2027 | Trial primary completion date: Jan 2026 --> Jan 2027
    Trial completion date • Trial primary completion date
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    EGFR (Epidermal growth factor receptor) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • 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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    CDKN2A deletion • BRIP1 mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • IDH wild-type
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    Keytruda (pembrolizumab) • Lynparza (olaparib) • temozolomide
    3ms
    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: Feb 2026 --> Dec 2029 | Trial primary completion date: Feb 2026 --> Dec 2029
    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)
    4ms
    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
    |
    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
    |
    Lynparza (olaparib)
    4ms
    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
    5ms
    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)
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    cisplatin
    5ms
    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
    |
    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)
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    cisplatin