HISTOLOGY AND HISTOPATHOLOGY

Cellular and Molecular Biology

Review

Involvement of the phosphoinositide 3-kinase/Akt signaling pathway in the resistance to therapeutic treatments of human leukemias

A.M. Martelli1,2, G. Tabellini1, R. Bortul3, P.L. Tazzari4, A. Cappellini1, A.M. Billi1 and L. Cocco1

1Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell’Apparato Locomotore, Sezione di Anatomia Umana, Cell signalling Laboratory, Università di Bologna, Bologna, Italy, 2Istituto per i Trapianti d’Organo e l’Immunocitologia del C.N.R., Sezione di Bologna c/o IOR, Bologna, Italy, 3Dipartimento di Morfologia Umana Normale, Università di Trieste, Trieste, Italy and 4Servizio di Immunoematologia e Trasfusionale, Policlinico S.Orsola-Malpighi, Bologna

Offprint requests to: Alberto M. Martelli, Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell’Apparato Locomotore, Università di Bologna, via Irnerio 48, 40126 Bologna, Italy. Fax: +39-0512091695. e-mail: amartell@biocfarm.unibo.it


Summary. A major factor undermining successful cancer treatment is the occurrence of resistance to conventional treatments such as chemotherapy and ionizing radiation. Evidence accumulated over the recent years has indicated the phosphoinositide 3-kinase/Akt signal transduction pathway as one of the major factors implicated in cancer resistance to conventional therapies. Indeed, the phosphoinositide 3-kinase/Akt axis regulates the expression and/or function of many anti-apoptotic proteins which strongly contributes to cancer cell survival. As a result, small molecules designed to specifically target key components of this signaling network are now being developed for clinical use as single therapeutic agents and/or in combination with other forms of therapy to overcome resistance. Initially, the phosphoinositide 3-kinase/Akt signal transduction pathway has been mainly investigated in solid tumors. Recently, however, this network has also been recognized as an important therapeutic target in human leukemias. Specific inhibition of this signalling pathway may be a valid approach to treat these diseases and increase the efficacy of standard types of therapy. Histol Histopathol 20, 239-252 (2005)

Key words: PI3K/Akt, Signal transduction, Phosphorylation, Resistance, Apoptosis

DOI: 10.14670/HH-20.239