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Critical Reviews™ in Oncogenesis
SJR: 0.946 SNIP: 0.503 CiteScore™: 2

ISSN Imprimir: 0893-9675
ISSN En Línea: 2162-6448

Critical Reviews™ in Oncogenesis

DOI: 10.1615/CritRevOncog.2016016966
pages 269-308

Strategies to Strike Survival Networks in Cancer

Marzia Pennati
Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Graziella Cimino-Reale
Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Laura Gatti
Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy
Giuliana Cassinelli
Molecular Pharmacology Unit, Department of Experimental Oncology and Molecular Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

SINOPSIS

The machinery that maintains cellular and tissue homeostasis in a healthy individual is recruited and hijacked by cancer cells to support tumor growth and progression. Activation of often unpredictable alternative or complementary signaling pathways allows cancer cells to bypass the intrinsic self-destructive machinery and the limited replicative potential present in every cell for correct homeostasis maintenance. Therefore, evasion/resistance to apoptosis/cell death, self-sufficiency in growth/survival signals, and limitless replicative potential remain undoubted hallmarks of cancer, contributing to drug resistance. Herein, we specifically review antitumor strategies involving agents targeting deregulated receptor tyrosine kinases, selected epigenetic modifications, the ubiquitin-proteasome system, the unfolded protein response, the apoptotic pathway, and peculiar nucleic acid structures, with the aim of highlighting the mechanisms underlying favorable drug interaction. In this context, we focus on preclinical studies that have already been translated into clinical investigation. Particular emphasis is devoted to strategies effective in solid tumors because of the peculiarity and distinctive features of solid tumors in terms of drug delivery and relative to the impact of the tumor microenvironment.