Melflufen, a peptide ‐conjugated alkylator, is an efficient anti‐neo‐plastic drug in breast cancer cell lines

Melflufen is a lipophilic peptide ‐conjugated alkylator that is converted by aminopeptidases inside cells to hydrophilic melphalan metabolites. Melflufen is currently in clinical trials in late stage myeloma where it has shown promising effects. However, studies on the effect of melflufen on solid tumors are limited. Here, we have analyzed the efficacy of melflufen in isogenic normal and cancerous breast epithelial lines as well as the triple‐negative MDA‐MB‐231 in 2D, 3D and in vivo. Our data shows that Melflufen is more potent then Melphalan or Doxorubicin and its efficacy is facilitated by aminopeptidases. AbstractMelphalan flufenamide (hereinafter referred to as “melflufen”) is a peptide‐conjugated drug currently in phase 3 trials for the treatment of relapsed or refractory multiple myeloma. Due to its lipophilic nature, it readily enters cells, where it is converted to the known alkylator melphalan leading to enrichment of hydrophilic alkylator paylo ads. Here, we have analysed in vitro and in vivo the efficacy of melflufen on normal and cancerous breast epithelial lines. D492 is a normal‐derived nontumorigenic epithelial progenitor cell line whereas D492HER2 is a tumorigenic version of D492, overexpressing the HER2 oncogene. In addition we us ed triple negative breast cancer cell line MDA‐MB231. The tumorigenic D492HER2 and MDA‐MB231 cells were more sensitive than normal‐derived D492 cells when treated with melflufen. Compared to the commonly used ...
Source: Cancer Medicine - Category: Cancer & Oncology Authors: Tags: ORIGINAL RESEARCH Source Type: research