Akt is selectively activated in NSCLC tissues vs. surrounding lung tissues and confers a poor prognosis for patients with NSCLC. Although no Akt inhibitors exist, other inhibitors of the PI3K/Akt/mTOR pathway are avialable for clinical testing. A series of protocols utilizing pathway inhibitors used either as single agents or in combination with other standard chemotherapies has been put forward in the approval processes that are required to open protocols at the Clinical Research Center and at the National Navlal Medical Center. Currently, there is a Phase I trial of nelfinavir in subjects with relapsed for refractory solid tumors that is open at the Clinical Research Center. This protocol is based on our preclinical studies that showed that nelfinavir is an effective anti-cancer agent in vitro and in vivo that works through multiple mechanisms including Akt inhibition and the induction of apoptosis, ER stress and autophagy.
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| LoPiccolo, Jaclyn; Blumenthal, Gideon M; Bernstein, Wendy B et al. (2008) Targeting the PI3K/Akt/mTOR pathway: effective combinations and clinical considerations. Drug Resist Updat 11:32-50 |
| LoPiccolo, Jaclyn; Granville, Courtney A; Gills, Joell J et al. (2007) Targeting Akt in cancer therapy. Anticancer Drugs 18:861-74 |
| Lopiccolo, Jaclyn; Ballas, Marc S; Dennis, Phillip A (2007) PTEN hamartomatous tumor syndromes (PHTS): rare syndromes with great relevance to common cancers and targeted drug development. Crit Rev Oncol Hematol 63:203-14 |
| O'Mahony, Deirdre; Dennis, Phillip A (2006) Using immunotherapy to target EGF in patients with NSCLC. Cancer Biol Ther 5:150-1 |
| Tsurutani, Junji; Ballas, Marc S; Dennis, Phillip A (2006) Overestimating the influence of the 1999 WHO classification of lung tumors on survival in bronchioloalveloar carcinoma. J Clin Oncol 24:1963; author reply 1963-4 |
| Tsurutani, Junji; Ballas, Marc; Steinberg, Seth M et al. (2006) Gefitinib for refractory advanced non-small-cell lung cancer. Lancet 367:300 |
| Tsurutani, Junji; Fukuoka, Junya; Tsurutani, Hiroko et al. (2006) Evaluation of two phosphorylation sites improves the prognostic significance of Akt activation in non-small-cell lung cancer tumors. J Clin Oncol 24:306-14 |
