Commentary: CVM-1118 (foslinanib), a 2-phenyl-4-quinolone derivative, promotes apoptosis and inhibits vasculogenic mimicry via targeting TRAP1

In this issue of Pathology & Oncology Research [1], Shen and colleagues report on a novel drug, CVM-1118 (generic name foslinanib), which is a phosphoric ester compound selected from 2-phenyl-4-quinolone derivatives. The major active metabolite of CVM-1118 is CVM-1125, which has shown inhibitory and cytotoxic effects at nanomolar range. Targeting tumor growth and metastasis has been a challenging endeavor for cancer 51 researchers and oncologists. Over time, several approaches have been executed -each 52 with their own merit, that have incrementally advanced the field. These include, but are 53 not limited to: radiation therapy, hormone therapy, chemotherapy, angiogenesis inhibitor 54 therapy, targeted molecular therapies, and immunotherapy. Although many patients have 55 benefitted from these types of therapies, the most aggressive forms of cancer evolve as 56 resistant over time, suggesting that plasticity and heterogeneity must be considered as a 57 major factor in developing the most effective customized approach.A noteworthy example of tumor cell plasticity is vasculogenic mimicry, originally described 60 in human metastatic melanoma [2], and then validated across a wide spectrum of 61 aggressive forms of cancer [3]. At the time this new concept was introduced, angiogenesis 62 inhibitor therapy -targeting newly formed angiogenic vasculature, was considered novel 63 [4]. However, many patients with aggressive forms of cancer did not fully respond to this 64 new therapy [5,6]. We hypothesized that tumor cells engaged in vasculogenic mimicry,