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216 Advances in Cancer Therapy

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Fig. 2. Schematic representation of molecular mechanisms of novel strategies aimed at restoring TRAIL sensitivity of haematological malignancies. RAD: radiotherapy; CHT:

A number of preliminary studies sustain the use of TRAs instead of rTRAIL in the treatment of tumour cells protected from TRAIL-induced apoptosis by the expression of cell surface decoy receptors. Although the early clinical trials are promising and well tolerated, it is worth outlining that the utility of both rTRAIL and agonistic anti-TRAIL-Rs antibodies therapies is restricted to patients with TRAIL-sensitive tumours. To restore TRAIL sensitivity in cancer cells novel compounds have been identified and are currently used in combined protocols with TRAIL ligand/TRAs or conventional radio-chemotherapy. Once mechanisms of action/resistance to TRAIL signalling are better understood, approaches to predict patient response and optimize combination regimens may be developed to overcome primary and acquired resistance on the trail to a personalized treatment of cancer.

chemotherapy. See text for other abbreviations.

**6. Conclusion** 

effects compared to conventional radio-chemotherapy.


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**11**

*Italy* 

**Therapeutical Cues from** 

Stefano Marastoni, Eva Andreuzzi,

**the Tumor Microenvironment** 

Roberta Colladel, Alice Paulitti, Alessandra Silvestri,

*Experimental Oncology Division 2, CRO-IRCCS, Aviano* 

Federico Todaro, Alfonso Colombatti and Maurizio Mongiat

The tumor can be considered a complex organ where transformed cells characterized by high genomic instability and altered gene expression are interconnected and communicate with the surrounding microenvironment. The microenvironment (Fig. 1) is composed of a large variety of stromal cells including inflammatory, stem and progenitor cells, fibroblasts, myofibroblasts, perycites, endothelial and mural cells of the blood vessels which are interconnected with the components of the extracellular matrix (ECM). The crosstalk between these components and cancer cells deeply affects their survival and proliferation. Due to the critical role of these interactions in cancer progression, each cellular or molecular component represents a potential target for the development of useful drugs in cancer treatment. The cells of the microenvironment are more genetically stable compared to the

Fig. 1. Schematic representation of the tumor microenvironment; CAF: Cancer Associated

Fibroblasts; ECM: extracellular matrix.

**1. Introduction** 

