Abstract
Metastasis represents the most lethal attribute of cancer and critically limits successful therapies in many tumor entities. The clinical need is defined by the fact that all cancer patients, who have or who will develop distant metastasis, will experience shorter survival. Thus, the ultimate goal in cancer therapy is the restriction of solid cancer metastasis by novel molecularly targeted small molecule based therapies. Biomarkers identifying cancer patients at high risk for metastasis and simultaneously acting as key drivers for metastasis are extremely desired. Clinical interventions targeting these key molecules will result in high efficiency in metastasis intervention. In result of this, personalized tailored interventions for restriction and prevention of cancer progression and metastasis will improve patient survival. This review defines crucial biological steps of the metastatic cascade, such as cell dissemination, migration and invasion as well as the action of metastasis suppressors. Targeting these biological steps with tailored therapeutic strategies of intervention or even prevention of metastasis using a wide range of small molecules will be discussed.
Highlights
Invasion and metastasis belong to the hallmarks of cancer, which severely limit therapeutic options and in result of this, limit patient survival
Colorectal cancer patients have a good prognosis if diagnosed before metastases have formed
Patients at high risk need to be identified by strong biomarkers, which are in the best scenario causative molecules for metastasis formation
Summary
Despite the progress for treatment of solid cancers, metastasis remains the key issue impacting failure or success of cancer therapies. We are focusing here on biomarkers acting as causal key drivers for metastasis, being involved in signaling pathways, promoting and driving the metastatic phenotype of cancer cells, which may serve as useful targets for small molecule-based restriction of metastasis formation. Tumor cell detachment from the primary tumor mass is caused by loss of adhesion programs and invasion in the adjacent tissue is mainly characterized by degradation of the matrix using a variety of proteinases, both leading to increase in cell motility. We will review single key steps of the metastatic cascade in the context of signaling pathways, key biomarkers thereof and targeting by small molecule drugs aiming at these metastatic steps, which lead to metastasis restriction (Figure 1 and Table 1).
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
