Dear Colleagues,

Cells react to damage by eliciting stress response pathways aiming at restoring cell integrity; it is now becoming evident that such responses include homeostatic cues to also safeguard and restore integrity at a tissue level. A special response is Phoenix Rising, a compensatory proliferation mechanism where apoptotic cells themselves tutor repopulation after severe cell loss by promoting a caspase-3-PGE2-STAT3 signaling axis. Tumor tissues, heavily wounded by cytotoxic therapies, also set up such stress responses with the aim of reorganizing the “injured” tumor tissue in a pro-regenerative mode. In cancer cells, however, this implies the induction of extraordinary phenotypic plasticity, eliciting simil-embryonal phenomena of epithelial-to-mesenchymal transition and the appearance of (cancer) stem cells that, like preset “packages”, reprogram the epigenome. Unfortunately, this often mediates malignant progression, resistance to apoptosis, and metastatic spread, linking post-therapy cancer repopulation with acquired cell resistance, in addition to gene mutations. Intriguingly, emerging non-cytotoxic anticancer therapies (e.g., immuno-, hormone-, or molecular targeted-therapies) also elicit cancer tissue defense, promoting resistance. Attempts to target such phenomena are opening new space for therapeutic intervention aiming to counteract therapy-induced dysregulation of tumor tissue homeostasis. The scope of this Special Issue is to gather contributions on the mechanisms of therapy-promoted repopulation and cell resistance, focusing on the role of stress response and Phoenix Rising in cancer cell reprogramming.

Potential topics include but are not limited to:

• In vivo, in vitro, on-chip, and in silico modeling of post-therapy cancer repopulation and acquired cell resistance;
• Role of stress response to endogenous or therapy-promoted damage (e.g., hypoxia; DNA damage; nutrient deprivation; oxidations) in tumor repopulation and progression;
• Phoenix Rising pathway;
• Damage repair in cancer cells: adaptation vs. recovery;
• Signaling pathways involved in cancer tissue repopulation;
• Cancer Microenvironment in the response to anticancer therapies: role of damaged stroma and extracellular matrix;
• Therapy-induced cancer stem cells and epithelial-to-mesenchymal transition;
• Systemic effects elicited by stressed cancer tissue: vascularization, metabolic alterations, and immunological responses;
• Stress response and resistance acquisition in non-cytotoxic anticancer therapies;
• In vivo monitoring/imaging tumor tissue during response to tumor therapy.

Prof. Dr. Lina Ghibelli
Prof. Dr. Albrecht Reichle
Guest Editors

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• compensatory proliferation
• epithelial-to-mesenchymal transition
• cancer stem cells
• DNA damage response
• cancer tissue aberrant regeneration
• cancer microenvironment