Systems Biologic Implications of Metronomic Therapies in Cancer and Hematologic Neoplasia

Dear Colleagues,

Metronomic tumor therapy is the administration of drugs at the minimum biologically effective dose still leading to anti-tumor activity, given as a continuous dosing regimen with minimal drug-free breaks.

Well-tolerated by patients, metronomic regimens induce cancer cell reprogramming, ameliorating aberrant cancer tissue homeostasis, through cell-autonomous, tissue-autonomous, and systemic signalling, involving epithelial, stroma, and immune infiltrates, promoting long-term tumor control.

Reprogramming actions place metronomic therapy within emerging clinical approaches such as immunotherapy and anakoinosis, which promise durable responses by communicative reprogramming of tumor tissues and can be included in the ‘master modulators’ category of anticancer bio-modulatory drugs, i.e., transcriptional modulators; epigenetically modifying agents; and protein binding drugs, such as COX-2 inhibitors, IMiDs, metronomic chemotherapy, etc. Master modulators may mediate multi-level systems biologic effects on quite different topographic levels: the tumor’s different cell compartments; the tumor and the tumor-harboring organ; and, finally, the tumor and the whole organism.

A long record shows excellent clinical results for metronomic therapy in metastatic cancer. However, it is mostly unknown how bio-modulation is mechanistically achieved; this impairs focusing to improve the treatment.

The aim of this Special Issue is covering the multi-level effects of metronomic therapies in cancer and hematologic neoplasia to explore the mechanisms of bio-modulation. 

In particular, we welcome topics covering the interaction of ‘master modulators’ with the tumor, the tumor-harboring organ, and the organism:

• The bio-modulatory effects of metronomic therapy
• The role of stroma and immune infiltrates in the bio-modulatory effect of metronomic regimens
• The establishment of in vitro advanced tissue culture models for the study of metronomic therapy
• The mathematical modeling of metronomic therapy
• Mechanisms of the effects of low vs. high doses of anticancer drugs
• Drug repurposing in metronomic chemotherapy
• Metronomic therapy redirecting immune responses in the tumor compartment
• The modulation of tumor-associated angiogenesis by metronomic therapy
• The control of tumor-associated inflammation by metronomic therapy
• Metronomic therapy and the up-regulation of non-mutated tumor suppressor genes
• Epigenetic changes following metronomic approaches
• The relationship between metronomic therapy and other bio-modulatory anticancer approaches
• The specification and improvment response by combining ‘master modulators’
• Anakoinosis as a novel paradigm for cancer treatment: communicative reprogramming of homeostatic pathways and the induction of evolutionary conserved functions
  
  

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

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• Interferon-alpha
• Peroxisome-proliferator activated receptor alpha/gamma agonists
• Glucocorticoids
• All-trans retinoic acid
• Arsenic trioxide
• IMiDs
• COX-2 inhibitors
• Metronomic chemotherapy
• Epigenetically modifying agents, i.e., azacitidine, decitabine, etc.
• Liposomal encapsulated small oligonucleotide encoding small activating RNAs
• Combinations of master modulators
• Master modulators plus classic targeted therapy