Novel therapeutic approaches based on the targeting of microenvironment-derived survival pathways in human cancer: experimental models and translational issues.
It is a current idea that carcinogenesis as well as tumor progression are dynamic processes, which involve inherited as well as somatic mutations and include a continuing adaptation to different microenvironmental conditions. There is, in fact, rising evidence that tumor cells are under a persistent stress and that autocrine as well as microenvironment-derived survival factors play a substantial role for the final outcome of the tumor development as well as for response to the anti-tumor therapy. We will review current achievements on the molecular biology of the microenvironment-derived survival signaling and therapeutical approaches, which are presently under clinical development. By the use of plasma cell disorders as an outstanding clinical model, we will discuss the development of novel in vivo preclinical models which recapitulate the human bone marrow milieu. Finally, we will discuss several topics which appear to be relevant for a successful clinical translation of preclinical research in this specific field.
Tassone
Pierfrancesco
P
Medical Oncology Unit, Magna Graecia University and Cancer Center, Campus Germaneto, Catanzaro, Italy.
Tagliaferri
Pierosandro
P
Fulciniti
Maria Teresa
MT
Di Martino
Maria Teresa
MT
Venuta
Salvatore
S
D000818:Animals; D002450:Cell Communication / Q000187:drug effects* / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000187:drug effects* / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems / Q000379:methods* / Q000639:trends; D006801:Humans; D014176:Protein Biosynthesis / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D023041:Xenograft Model Antitumor Assays / Q000379:methods*