Re-purposing cryoablation: a combinatorial 'therapy' for the destruction of tissue.


Journal Article (Review)

It is now recognized that the tumor microenvironment creates a protective neo-tissue that isolates the tumor from the various defense strategies of the body. Evidence demonstrates that, with successive therapeutic attempts, cancer cells acquire resistance to individual treatment modalities. For example, exposure to cytotoxic drugs results in the survival of approximately 20-30% of the cancer cells as only dividing cells succumb to each toxic exposure. With follow-up treatments, each additional dose results in tumor-associated fibroblasts secreting surface-protective proteins, which enhance cancer cell resistance. Similar outcomes are reported following radiotherapy. These defensive strategies are indicative of evolved capabilities of cancer to assure successful tumor growth through well-established anti-tumor-protective adaptations. As such, successful cancer management requires the activation of multiple cellular 'kill switches' to prevent initiation of diverse protective adaptations. Thermal therapies are unique treatment modalities typically applied as monotherapies (without repetition) thereby denying cancer cells the opportunity to express defensive mutations. Further, the destructive mechanisms of action involved with cryoablation (CA) include both physical and molecular insults resulting in the disruption of multiple defensive strategies that are not cell cycle dependent and adds a damaging structural (physical) element. This review discusses the application and clinical outcomes of CA with an emphasis on the mechanisms of cell death induced by structural, metabolic, vascular and immune processes. The induction of diverse cell death cascades, resulting in the activation of apoptosis and necrosis, allows CA to be characterized as a combinatorial treatment modality. Our understanding of these mechanisms now supports adjunctive therapies that can augment cell death pathways.

Full Text

Duke Authors

Cited Authors

  • Baust, JG; Bischof, JC; Jiang-Hughes, S; Polascik, TJ; Rukstalis, DB; Gage, AA; Baust, JM

Published Date

  • June 2015

Published In

Volume / Issue

  • 18 / 2

Start / End Page

  • 87 - 95

PubMed ID

  • 25622539

Pubmed Central ID

  • 25622539

Electronic International Standard Serial Number (EISSN)

  • 1476-5608

Digital Object Identifier (DOI)

  • 10.1038/pcan.2014.54


  • eng

Conference Location

  • England