Journal Article

Rethinking the metastatic cascade as a therapeutic target

Sledge, George W., Mina, Lida A.

2011

نظرة عامة

The treatment of microscopic metastatic disease is based on the assumption that micrometastases and overt metastases will respond to the same interventions; however, clinical observations illustrate this assumption is incorrect. The authors discuss our existing understanding of the metastatic cascade, emerging therapeutic targets involved in the metastatic process, and how novel anti-metastatic therapies might be developed for clinical use. Metastasis is the leading cause of cancer death. The metastatic cascade is a complex yet inefficient process that we have only begun to understand in recent years. Several of the early steps of this cascade are not readily targetable in the clinic. Past therapeutic developmental strategies have not distinguished between micrometastases and overt metastases. This lack of understanding is apparent in therapies that have been developed for patients with metastatic disease that are not efficacious in patients with micrometastatic disease; that is, in the adjuvant setting. Moreover, drugs that target distant metastases often do not work in the adjuvant setting. This Review will discuss our current understanding of the metastatic cascade as it relates to therapy, emerging therapeutic targets in the metastatic process, and how novel antimetastatic therapies might be developed for clinical use. Key Points Targeting the right steps of the metastatic cascade is vital for successful clinical development in cancer Metastatic colonization is the pivotal transition between micrometastases and macrometastases; it constitutes the major target in the metastatic cascade Targetable processes and cells of the metastatic cascade include: the tumor microenvironment, the genetic background, angiogenesis, the immune axis, dormancy, and cancer-stem cells Metastases inhibitor trials should go beyond testing efficacy and safety, and include monitoring micrometastatic burden as well as assessing the ideal duration for the suppression of a specific target The basic assumption that what works in macrometastases will work for micrometastases needs to be revisited

• الناشر: Nature Publishing Group UK,Nature Publishing Group
• موضوع: 631/154/555 / 692/699/67/1059 / 692/699/67/322 / Animals / Antineoplastic Agents - therapeutic use / Biomarkers, Tumor - analysis / Cancer / Care and treatment / Humans / Medicine / Medicine & Public Health / Metastasis / Neoplasm Metastasis / Neoplasms - pathology / Neoplasms - therapy / Oncology / review-article