Peptides and small molecules blocking the CXCR4/CXCL12 axis overcome bone marrow ‑induced chemoresistance in acute leukemias.

Peptides and small molecules blocking the CXCR4/CXCL12 axis overcome bone marrow‑induced chemoresistance in acute leukemias. Oncol Rep. 2018 Oct 18;: Authors: Pillozzi S, Bernini A, Spiga O, Lelli B, Petroni G, Bracci L, Niccolai N, Arcangeli A Abstract Notable advances in treatment have been made and increases in the cure rates of pediatric leukemia have been achieved. However, the majority of children with relapsed disease are not expected to survive, with chemotherapy resistance acting as the principal cause of treatment failure. Interaction between leukemic cells and the bone marrow microenvironment is the primary cause of relapse. It was identified that a multi‑protein membrane complex, formed by potassium voltage‑gated channel subfamily H member 2 (hERG1) channels, the β1 integrin subunit and the stromal cell‑derived factor 12 (CXCL12) receptor, C‑X‑C chemokine receptor type 4 (CXCR4), exerts a role in mesenchymal stromal cell (MSC)‑mediated chemoresistance in pediatric leukemias. hERG1 blockade was able to overcome chemoresistance in vitro and in vivo. As an alternative strategy to overcome chemoresistance, the present study evaluated the effects of novel tools targeting the CXCR4/CXCL12 axis. The analysis of CXCL12 structural dynamics was used for the selection of a peptide (4‑1‑17) and a small molecule (8673), which interact with a transient hot spot, identified by a dynamic drug design approach. The prese...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research