^
    10ms
    An in vitro pharmacogenomic approach reveals subtype-specific therapeutic vulnerabilities in atypical teratoid/rhabdoid tumors (AT/RT). (PubMed, Pharmacol Res)
    Subtype-dependent drug response profiles demonstrated sensitivity of AT/RT-SHH cell lines to B-cell lymphoma 2 (BCL2) and heat shock protein 90 (HSP90) inhibitors, and increased activity of microtubule inhibitors, kinesin spindle protein (KSP) inhibitors, and the eukaryotic translation initiation factor 4E (eIF4E) inhibitor briciclib in a subset of AT/RT-MYC cell lines. In summary, our in vitro pharmacogenomic approach revealed preclinical evidence of tumor type- and subtype-specific therapeutic vulnerabilities in AT/RT cell lines that may inform future in vivo and clinical evaluations of novel pharmacological strategies.
    Preclinical • Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    Venclexta (venetoclax) • idasanutlin (RG7388) • tanespimycin (BMS-722782) • ABT-737 • briciclib (ON 013105) • GDC-0623
    10ms
    Myeloma-Developing Regimens Using Genomics (MyDRUG) (clinicaltrials.gov)
    P1/2, N=103, Completed, Multiple Myeloma Research Consortium | Recruiting --> Completed | N=228 --> 103 | Trial completion date: Feb 2024 --> Dec 2024 | Trial primary completion date: Feb 2022 --> Dec 2024
    Trial completion • Enrollment change • Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • SLC1A5 (Solute Carrier Family 1 Member 5)
    |
    Venclexta (venetoclax) • Cotellic (cobimetinib) • Verzenio (abemaciclib) • Balversa (erdafitinib) • Xpovio (selinexor) • Ninlaro (ixazomib) • Darzalex (daratumumab) • Idhifa (enasidenib) • pomalidomide • Blenrep (belantamab mafodotin-blmf) • GDC-0623
    2years
    High in vitro and in vivo activity of BI-847325, a dual MEK/Aurora kinase inhibitor, in human solid and hematologic cancer models. (PubMed, Cancer Res Commun)
    BI-847325 showed a broader range of activity than the MEK inhibitor GDC-0623. In conclusion, dual MEK/Aurora kinase inhibition shows remarkable potential for treating multiple types of hematological and solid tumors. The combination with capecitabine was synergistic in colorectal, gastric, and mammary cancer.
    Preclinical • Journal
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    BRAF mutation • NRAS mutation
    |
    capecitabine • BI 847325 • GDC-0623