About this Research Topic

Background

Tumors become lethal when they acquire various aggressive qualities that enable them to succeed in spreading throughout the body in a process known as metastasis. These newly aggressive cells are able to form tentacle-like structures called invadopodia. While mostly characterized in vitro, invadopodia have recently been determined to be involved in a key step of metastasis known as cancer cell extravasation. This process has been understudied relative to other fields in metastasis, but research efforts are growing to understand if this is a targetable feature specific to metastatic cancers. There is a strong belief in this community that invadopodia, if targeted, would lead to the first set of anti-metastasis drugs. The biochemistry and cellular mechanics involved in invadopodia within the context of metastasis are understood at a basic level and could be translated to druggable targets.

The present problem that this Research Topic hopes to address is how to collectively determine which components should be targeted to regulate invadopodia formation and function during metastatic spread. There are various drug candidates but their potential effectiveness in the clinic is unclear. Inhibition of invadopodia regulators, such as Src, Twist, PDGFR-, TKS-5, and IL-6/IL-8, can attenuate cancer metastasis in vivo. EGFR and kinase signaling inhibition achieved by clinically approved EGFR inhibitors, (e.g., erlotinib), HER-2 inhibitors (e.g., trastuzumab), and multi-kinase inhibitors (e.g, sunitinib), also exhibit anti-cancer efficacy partially by inhibiting invadopodia. Several groups have also developed novel invadopodia inhibitors by inhibiting factors such as CDK-5, TAO-3, or MT1-MMP (MMP-14). While these first-generation inhibitors have shown anti-metastasis efficacy in preclinical studies, none of them have successfully reached clinical trials thus far. It is thus imperative to gain further in-depth mechanistic insights into the regulatory mechanisms of invadopodia to identify novel druggable invadopodia targets. Novel invadopodia targets could be identified from large-scale screening efforts or structure-based design (for targets with accessible functional activities), antibody development (for membrane-based targets), or next-generation biological or gene-therapy agents.

We welcome Reviews, Mini Reviews and Perspective pieces that include, but are not limited to, the following list of themes:

● Novel targets that antagonize invadopodia function
● Invadopodia interactions with host vasculature
● Cancer cell extravasation mechanisms that are targetable
● Model systems and techniques for screening anti-invadopodia or anti-metastasis drugs
● Role of proteases released by invadopodia in cancer cell extravasation
● Kinase Inhibition for targeting invadopodia and extravasation
● Antibody therapies to inhibit invadopodia and halt metastatic spread
● Clinical trials with non-metastasis-free survival endpoints
● Prophylaxis and maintenance therapy in advanced metastatic disease
● Repurposing drugs for anti-invadopodia effects
● Universal/spurious role of invadopodia in metastasis
● Drug discovery efforts for inhibiting invadopodia

Keywords: invadopodia, drug development, drug validation, cancer cell extravasation, metastasis

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