[show abstract][hide abstract] ABSTRACT: Cancer is a diverse class of diseases which differ widely in their cause and biology. The aberrant behavior of cancer reflects up regulation of certain oncogenic signaling pathways that promote proliferation, inhibit apoptosis, and enable the cancer to spread and evoke angiogenesis. Phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway controls various biological processes that are important for normal functioning of the cell via cell cycle progression, survival, migration, transcription, translation and metabolism. However, PI3K signaling pathway is dysregulated almost in all cancers and dysregulation of this signaling is due to the amplification and genetic mutation of PI3K gene, encoding catalytic and regulatory subunit of PI3K isoforms. The current review focuses on the structural features of various PI3K isoforms including Akt and mTOR and their inhibition using specific small molecule inhibitors in an attempt to achieve an attractive target for cancer prevention and chemotherapy.
Anti-cancer agents in medicinal chemistry 02/2013;
[show abstract][hide abstract] ABSTRACT: Cancer cells compared to their normal counterparts reveal different metabolic needs and this differential
requirement of metabolic intermediates and their subsequent consequences require an elaborate understanding
of cancer cell metabolism and increased energy production in these cells. Nevertheless these metabolic
differences have provided opportunities for developing novel therapeutic approaches for the cancer diagnosis and
treatment. In addition enhanced proliferative capacities of tumor cells associated with aberrations of many signal
transduction pathways resulting from genetic or epigenetic alterations has made it possible to develop countless
targeted therapeutics for several types of malignancies. However at present most of our understanding about the
dysregulated cancer cell metabolism is at physiological stages. With advancement in technology development,
we may eventually be able to differentiate the metabolic differences between normal cells and cancerous at the
single-tumor level that may influence the development of personalized cancer medicine. In this review, the focal
point will be the recent developments in understanding the crucial role of metabolic enzymes, oncogenes and
tumor suppressor genes in progression of cancer and their targeting to establish the most appropriate therapeutic
strategies for better clinical outcome.
Journal of Cancer Science and Therapy 08/2012; 4(9):281-291.
[show abstract][hide abstract] ABSTRACT: Cancer is a pathologic condition that involves genetic and epigenetic events culminating in neoplastic transformation. Alteration in epigenetic events that regulate the transcriptional activity of genes associated with various signaling pathways can influence multiple stages of tumorigenesis. In cancer cells, an imbalance often exists between histone acetyl transferase and histone deacetylase (HDAC) activities, and current research focuses actively on seeking competitive HDAC inhibitors (HDACi) for chemotherapeutic intervention. HDACi are proving useful for cancer prevention and therapy by virtue of their ability to reactivate the expression of epigenetically silenced genes, including those involved in differentiation, cell cycle regulation, apoptosis, angiogenesis, invasion, and metastasis. Furthermore, epidemiological studies suggest that different diets such as intake of cruciferous vegetables may lower the risk of different cancers, and there is growing interest in identifying the specific chemoprotective constituents and mechanistic insights of their action. Interestingly, it has been observed that cancer cells are more sensitive than nontransformed cells to apoptotic induction by some HDACi. Although the mechanistic basis for this sensitivity is unclear, yet HDACi have emerged as important epigenetic target for single and combinatorial chemotherapy. HDACi derived from diverse sources such as microbial, dietary, and synthetic increase acetylation level of cells and bring about anti-proliferative and apoptotic effects specific to cancer cells by way of their role in cell cycle regulation and expression of epigenetically silenced genes.
DNA and cell biology 03/2012; 31 Suppl 1:S62-71. · 2.28 Impact Factor