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melphalan + carfilzomib + thalidomide + dexamethasone + cisplatin + doxorubicin + cyclophosphamide + etoposide + peripheral blood stem cells

Development stage
Preclinical
Lead developer
GSK
Modality
Stem Cell Therapies → Cell Therapies, Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a multi-agent combination regimen consisting of eight chemotherapeutic drugs—melphalan, carfilzomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide—administered alongside autologous peripheral blood stem cell transplantation. Each component has a distinct mechanism of action: - Melphalan and cyclophosphamide are alkylating agents that cause DNA crosslinking and cell death. - Carfilzomib is a proteasome inhibitor that disrupts protein degradation in cancer cells. - Thalidomide is an immunomodulatory agent with antiangiogenic properties. - Dexamethasone is a synthetic glucocorticoid with anti-inflammatory and cytotoxic effects on lymphoid cells. - Cisplatin forms DNA adducts leading to apoptosis. - Doxorubicin intercalates into DNA and inhibits topoisomerase II. - Etoposide inhibits topoisomerase II causing double-strand breaks in DNA. Peripheral blood stem cells are used for hematopoietic rescue following high-dose chemotherapy. This intensive regimen may be considered for the treatment of multiple myeloma or other aggressive hematologic malignancies in the context of clinical trials or specialized protocols. The combination aims to maximize tumor cytoreduction before or after autologous stem cell transplantation.

02

Targets

TOP2A (DNA topoisomerase II)DNAGR (Glucocorticoid receptor)PSMB5 (Proteasome subunit beta Type-5)CRBN (Cereblon)

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