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    9ms
    A Highly Anticipated Selective Therapeutic Agent against CDK2: INX-315. (PubMed, Cancer Discov)
    This agent shows promise in CCNE1-amplified cancers and in CDK4/6 inhibitor-resistant breast cancers. See related article by Dietrich et al., p. 446 (8).
    Journal
    |
    CCNE1 (Cyclin E1) • CDK2 (Cyclin-dependent kinase 2)
    |
    CCNE1 amplification
    |
    INX-315
    12ms
    INX-315, a selective CDK2 inhibitor, induces cell cycle arrest and senescence in solid tumors. (PubMed, Cancer Discov)
    Using cell-based assays, patient-derived xenografts, and transgenic mouse models, we show that INX-315 (i) promotes retinoblastoma protein hypo-phosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth; (ii) overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control whilst re-instating the chromatin architecture of CDK4/6i-induced TIS; and (iii) delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets. Our results support the clinical development of selective CDK2 inhibitors.
    Journal
    |
    CCNE1 (Cyclin E1)
    |
    CCNE1 amplification
    |
    INX-315
    over1year
    INX-315-01: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (clinicaltrials.gov)
    P1/2, N=81, Recruiting, Incyclix Bio | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCNE1 (Cyclin E1)
    |
    HER-2 negative • CCNE1 amplification
    |
    INX-315
    over1year
    INX-315-01: Open-Label Study to Evaluate the Safety, Tolerability, PK, and Efficacy of INX-315 in Patients With Advanced Cancer (clinicaltrials.gov)
    P1/2, N=81, Not yet recruiting, Incyclix Bio
    New P1/2 trial • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • CCNE1 (Cyclin E1)
    |
    HER-2 negative • CCNE1 amplification
    |
    INX-315