Abstract
The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a central role in growth, proliferation, and anti-apoptotic mechanisms to promote cell cycle and survival not only in normal cells but also in a variety of tumor cells. Thus, the PI3K/Akt pathway, including the downstream effectors, may be a critical target for cancer therapy. Although this pathway has been investigated rigorously and dissected in detail in many physiological systems, its role in molecular target therapy for cancer remains to be established. Hematological malignancies such as leukemia, lymphoma, and myeloma can be ideal models for molecular targeting therapy because of the ease in obtaining samples for examining the effect of inhibitors of target molecules with critical roles in tumor growth and progression. In fact, several inhibitors, such as imatinib in Philadelphia chromosome-positive leukemia and bortezomib in multiple myeloma, have proved quite useful in clinics. Because the PI3K/Akt pathway is active in various hematological malignancies, inhibitors related to this pathway have been confirmed to induce apoptosis in these tumor cells. Efforts to exploit selective inhibitors of the PI3K/Akt pathway that show effectiveness and safety in the clinical setting are underway. We review the recent progress in molecular targeting therapy for the PI3K/Akt pathway in hematologic malignancies.
Keywords: PI3K, Akt, molecular targeting therapy, hematologic malignancies
Anti-Cancer Agents in Medicinal Chemistry
Title: The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies
Volume: 9 Issue: 5
Author(s): Kiyotaka Kawauchi, Toshie Ogasawara, Masako Yasuyama, Kuniaki Otsuka and Osamu Yamada
Affiliation:
Keywords: PI3K, Akt, molecular targeting therapy, hematologic malignancies
Abstract: The phosphatidylinositol 3-kinase (PI3K)/Akt pathway plays a central role in growth, proliferation, and anti-apoptotic mechanisms to promote cell cycle and survival not only in normal cells but also in a variety of tumor cells. Thus, the PI3K/Akt pathway, including the downstream effectors, may be a critical target for cancer therapy. Although this pathway has been investigated rigorously and dissected in detail in many physiological systems, its role in molecular target therapy for cancer remains to be established. Hematological malignancies such as leukemia, lymphoma, and myeloma can be ideal models for molecular targeting therapy because of the ease in obtaining samples for examining the effect of inhibitors of target molecules with critical roles in tumor growth and progression. In fact, several inhibitors, such as imatinib in Philadelphia chromosome-positive leukemia and bortezomib in multiple myeloma, have proved quite useful in clinics. Because the PI3K/Akt pathway is active in various hematological malignancies, inhibitors related to this pathway have been confirmed to induce apoptosis in these tumor cells. Efforts to exploit selective inhibitors of the PI3K/Akt pathway that show effectiveness and safety in the clinical setting are underway. We review the recent progress in molecular targeting therapy for the PI3K/Akt pathway in hematologic malignancies.
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Cite this article as:
Kawauchi Kiyotaka, Ogasawara Toshie, Yasuyama Masako, Otsuka Kuniaki and Yamada Osamu, The PI3K/Akt Pathway as a Target in the Treatment of Hematologic Malignancies, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (5) . https://dx.doi.org/10.2174/187152009788451851
DOI https://dx.doi.org/10.2174/187152009788451851 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
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