GCS-100 + etoposide + dexamethasone

GCS-100 + etoposide + dexamethasone is a combination regimen comprising three components: GCS-100, etoposide, and dexamethasone. - **GCS-100** is a *galectin-3 antagonist* derived from modified citrus pectin that binds and inhibits galectin-3, a protein implicated in tumor cell survival, drug resistance, and proliferation[1][2][5][7]. Its mechanism involves induction of apoptosis (via caspase-8 and -9 activation, downregulation of anti-apoptotic proteins such as MCL-1 and BCL-XL, upregulation of pro-apoptotic NOXA, and inhibition of cell cycle progression), as well as inhibition of key pathways such as NF-κB and AKT signaling[1][3][5]. GCS-100 has been specifically shown to sensitize tumor cells (including lymphoma and myeloma) to chemotherapy by disrupting galectin-3-mediated protection[2][7]. - **Etoposide** is a *topoisomerase II inhibitor* that exerts cytotoxicity by causing DNA strand breaks and preventing DNA religation in rapidly dividing cells. - **Dexamethasone** is a *synthetic glucocorticoid* that induces apoptosis in lymphoid malignancies and exerts anti-inflammatory and immunosuppressive effects. Combination of GCS-100 with dexamethasone and/or chemotherapeutic agents like etoposide has shown enhanced cytotoxicity and apoptosis in preclinical myeloma and lymphoma models, potentially overcoming drug resistance[5][7]. This regimen is being explored primarily in hematologic cancers such as multiple myeloma and lymphoma.