Countering chemo-induced metastasis
Two independent research teams have elucidated mechanisms by which cisplatin and paclitaxel can promote lung metastases in mice, providing links between the chemotherapies and the known metastatic effects of upregulating VEGF receptor 1 and matrix metalloproteinase 9, which acts downstream of the receptor.1,2
The findings could create additional uses for inhibitors of VEGF receptor 1 (FLT1; VEGFR-1) and revive work on matrix metalloproteinase (MMP) inhibitors, a class of beleaguered cancer compounds that has all but disappeared from development.
Multiple preclinical studies have shown that chemotherapy can promote metastatic tumor growth,3-5 and a handful of clinical trials have suggested chemotherapy can accelerate the growth of cancer cells.6,7
In the past five years, researchers have shown that chemotherapy can increase levels of circulating endothelial progenitor cells that contribute to tumor regrowth and angiogenesis,8,9and they have shown that these progenitor cells correlated with tumor progression and poor survival in patients.10
Despite the known link, the molecular mechanisms underlying chemotherapy's tumorigenic and prometastatic effects remained unclear. Part of the reason was that most studies had tracked the