Migrastatics—Anti-metastatic and Anti-invasion Drugs: Promises and Challenges

Trends

Local invasion and metastasis, rather than clonal proliferation, are the dominant features of solid cancer. However, a specific category of anti-invasion and antimetastatic drugs is missing for treatment of solid cancer

We propose the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasiveness and, consequently, with their ability to metastasize (e.g., inhibiting not only local invasion, but also extravasation and metastatic colonization).

In solid cancer, drug resistance is the main cause of treatment failure, and is attributed to mutations of the target. Since targeting the cause, although academically desirable, may be futile, a pragmatic and near-term option is to move downstream, to common denominators of cell migration and/or invasion, such as actin polymerization and actomyosin-mediated contractility.

In solid cancers, invasion and metastasis account for more than 90% of mortality. However, in the current armory of anticancer therapies, a specific category of anti-invasion and antimetastatic drugs is missing. Here, we coin the term ‘migrastatics’ for drugs interfering with all modes of cancer cell invasion and metastasis, to distinguish this class from conventional cytostatic drugs, which are mainly directed against cell proliferation. We define actin polymerization and contractility as target mechanisms for migrastatics, and review candidate migrastatic drugs. Critical assessment of these antimetastatic agents is warranted, because they may define new options for the treatment of solid cancers.