Effective PI3K modulators for improved therapy against malignant tumors and for neuroprotection of brain damage after tumor therapy (Review).
Due to the key role in various cellular processes including cell proliferation and cell survival on many cell types, dysregulation of the PI3K/AKT pathway represents a crucial step of the pathogenesis in many diseases. Furthermore, the tumor suppressor PTEN negatively regulates the PI3K/AKT pathway through its lipid phosphatase activity, which is recognized as one of the most frequently deleted and/or mutated genes in human cancer. Given the pervasive involvement of this pathway, the development of the molecules that modulate this PI3K/AKT signaling has been initiated in studies which focus on the extensive effective drug discovery. Consequently, the PI3K/AKT pathway appears to be an attractive pharmacological target both for cancer therapy and for neurological protection necessary after the therapy. A better understanding of the molecular relations could reveal new targets for treatment development. We review recent studies on the features of PI3K/AKT and PTEN, and their pleiotropic functions relevant to the signaling pathways involved in cancer progress and in neuronal damage by the therapy.
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Satoru
S
Matsuda
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Mayuko
M
Ichimura
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Mako
M
Ogino
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Noriko
N
Nakano
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Akari
A
Minami
Department of Microbiology and Immunology and Department of Genome Biology, Graduate School of Medicine, Osaka University, Suita, Osaka 565-0871, Japan.
Toshiyuki
T
Murai
Department of Food Science and Nutrition, Nara Women's University, Kita-Uoya Nishimachi, Nara 630-8506, Japan.
Yasuko
Y
Kitagishi
D000818:Animals; D001927:Brain Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology; D003131:Combined Modality Therapy / Q000009:adverse effects*; D006801:Humans; D058990:Molecular Targeted Therapy; D009369:Neoplasms / Q000378:metabolism / Q000628:therapy*; D000066829:Neuroprotection / Q000187:drug effects*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects
D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors