Anti-Cancer Drugs
Targeting Akt in cancer therapy
Jaclyn LoPiccolo, Courtney A. Granville, Joell J. Gills and Phillip A. Dennis
Anti-Cancer Drugs 2007, 18:861–874
In an effort to improve therapeutic options in cancer, many investigational drugs are being developed to inhibit signalling pathways that promote the survival of cancer cells. The prototypic pathway that promotes cellular survival is the phosphoinositide 30-kinase/Akt/mammalian target of rapamycin pathway, which is constitutively activated in many types of cancers. Mechanisms for activation of the serine/threonine kinase, Akt, include loss of tumor suppressor PTEN (phosphatase and tensin homolog deleted on chromosome 10) function, amplification or mutation of phosphoinositide 30-kinase, amplification of Akt, activation of growth factor receptors and exposure to carcinogens. Activation of Akt promotes cellular survival as well as resistance to treatment with chemotherapy and/or radiation therapy. Immunohistochemical analyses have shown that Akt is activated in many types of cancers and preneoplastic lesions, and Akt activation is a poor prognostic factor in various cancers. Taken together, these data demonstrate that Akt is a valid target for inhibition. This review will focus on published data using different approaches to inhibit Akt. We will also consider how the complex regulation of the phosphoinositide 30-kinase/Akt/mammalian target of rapamycin pathway poses practical issues concerning the design of clinical trials, potential toxicities and the likelihood of finding a therapeutic index when targeting such a critical cellular pathway. Read this article
Journal Spotlight
Intervention, published thrice yearly, is an international multi-disciplinary journal of mental health, psychosocial work and counseling in areas of armed conflict. The audience includes mental health workers such as psychiatrists, psychotherapists and psychiatric nurses, and also for counselors, psychosocial workers and community workers, staff members of NGO's developing mental health or psychosocial projects, and international experts in the field. Intervention is a publication of the War Trauma Foundation.
EISSN: 1872-1001
Frequency: 3 issues per year
Editor: Peter Ventevogel
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