Prodding the Beast: Assessing the Impact of Treatment-Induced Metastasis

The arsenal of treatments for most cancers fit broadly into the categories of surgery, chemotherapy, radiation, and targeted therapy. All represent proven and successful strategies, yet each can trigger local (tumor) and systemic (host) processes that elicit unwanted, often opposing, influences on cancer growth. Under certain conditions, nearly all cancer treatments can facilitate metastatic spread, often in parallel (and sometimes in clear contrast) with tumor reducing benefits. The paradox of treatment-induced metastasis (TIM) is not new. Supporting preclinical studies span decades, but are often overlooked. With recent evidence of prometastatic effects following treatment with targeted agents blocking the tumor microenvironment, a closer inspection of this literature is warranted. The TIM phenomena may diminish the impact of effective therapies and play a critical role in eventual resistance. Alternatively, it may simply exemplify the gap between animal and human studies, and therefore have little impact for patient disease and treatment. This review will focus on the preclinical model systems used to evaluate TIM and explore the mechanisms that influence overall treatment efficacy. Understanding the role of TIM in established and emerging drug treatment strategies may help provide rationales for future drug combination approaches with antimetastatic agents to improve outcomes and reduce resistance.