Blood: Salbonate enhances the anti-tumor activity of CRM1 inhibitors

Chromosomal region maintenance protein 1 (CRM1) mediated protein output from the nuclei of cells, is a new target for cancer treatment.
KPT-330 (Selinexor) is the first type of inhibitor of CRM1 and was recently approved for relapsed multiple myeloma and diffuse large B-cell lymphoma, but its widespread use is limited by its high toxicity.
KPT-330-CS enhances the anti-tumor effect of CRM1 inhibitors, Abeykoon and others found that salbonate significantly enhances the anti-tumor activity of CRM1 inhibitors by extending the action mechanism beyond the inhibition mechanism to suppress CRM1.
Selinexor, when used in a combined way with salbonate, can target a range of blood tumors at lower doses and can also reduce clinical adverse reactions.
KPT-330-CS showed strong broad-spectrum activity of high-risk blood malignancies and solid tumors in vivo/externally, with no significant organ toxicity of saloid choline (CS) and low-dose KPT-330 (K-CS).
compared with malignant cells, the combination of K-CS is non-toxic to non-malignant cells and non-toxic to normal organs in mice.
KPT-330-CS significantly improves the mechanism of anti-tumor activity in patient samples, compared to the single use of KPT-330, K-CS can inhibit the expression of CRM1, RAD51 and thoracic nucleotide synthase proteins, thus more effectively inhibiting CRM1-mediated nuclear output, DNA damage repair, reducing synthesium synthesis, so that the cell cycle stalls in phase S, resulting in apoptosis.
addition, the addition of PARP inhibitors can further enhance the anti-tumor effect of K-CS.
addition, K-CS represents a new treatment for many types of blood cancer and will facilitate future research to treat cancer using DNA damage repair and nuclear transport.