Revisiting perioperative chemotherapy: the critical importance of targeting residual cancer prior to wound healing

If cancer cells can hijack the wound healing process to facilitate their metastatic spread and survival, then the period immediately after surgery may be a particularly vulnerable period of time for the host, as wound healing pathways are activated and amplified after the primary tumor is removed. Given that we often wait 30 days or more after surgical removal of the primary tumor before initiating adjuvant chemotherapy to allow time for the wound to heal, this paper challenges the wisdom of that clinical paradigm, providing a theoretical rationale for administering therapy during the perioperative period.Waiting for wound healing to occur before initiating adjuvant therapies may be seriously compromising their effectiveness, and patients subsequently rendered incurable as a result of this wait. Clinical trials to establish the safety and effectiveness of administering adjuvant therapies perioperatively are needed. These therapies should target not only the residual cancer cells, but also the wound healing pathway utilized by these cells to proliferate and metastasize.Cancer has been described as a "wound that won't heal' [1], and general similarities between the behavior of a cancerous tumor and wound healing have been recognized for over a century [2]. Normal wound healing is an adaptive process that requires the integration of multiple distinct cellular behaviors, including cell-cell dissociation; cellular proliferation and migration; angiogenesis; matrix degradation and synthesis; and cell survival during the anchorage independent conditions associated with cellular migration [3]. Diverse and specialized cells – including epithelial cells, fibroblasts, endothelial cells, inflammatory cells, and bone marrow derived progenitor cells – orchestrate this complex process in a temporally coordinated pattern to repair damaged tissue [3]. They communicate with each other through a myriad of cytokines, chemokines and growth factors that act in both a paracrine and autocri