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The role of oncogenic kinases in human cancer (Review)
1Medical School, University of Crete, 71409 Heraklion, Crete, Greece.
Abstract:
Tumorigenesis in humans is a multistep process, which reflects genetic alterations that lead to cell transformation and malignancy. Cellular genes that are altered are normally involved in maintaining cell homeostasis by participating in signaling pathways tightly regulated to maintain the functional integrity of the cell. When these genes are altered they escape from the regulatory control and transmit signals that lead to the progressive conversion of normal cells into cancer cells. Oncogenic signals involve activation of kinases, which can be either a primary event when they are directly mutated in a tumor cell or a secondary event as recipients and mediators of oncogenic signals. Transmembrane (e.g. EGFR, PDGFR) or cytoplasmic (Src, Abl) tyrosine kinases are found mutated in a variety of human tumors. Cytoplasmic serine threonine kinases (Raf, Akt, Tpl-2) are also mutated or activated in several types of human malignancies. Kinases transduce signals that lead to cell proliferation or inhibition of programmed cell death by activating transcription factors (e.g. AP1, NFkappaB, Myc), inhibiting pro-apoptotic molecules (e.g. Bad, Bax), or they participate in deregulating the cell cycle control. Thus, kinases play a central role in oncogenesis rendering them putative targets for anti-cancer drug design.
Insights
Genetic alterations in human tumors activate kinases, crucial signaling proteins that drive cell growth and survival. Understanding these kinase activations is key for developing targeted anti-cancer drugs.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Tumorigenesis involves genetic alterations disrupting normal cell homeostasis.
- Altered cellular genes in cancer cells activate signaling pathways, promoting malignancy.
- Kinases are key mediators of oncogenic signals, regulating cell proliferation and survival.
Purpose of the Study:
- To elucidate the role of kinases in human tumorigenesis.
- To highlight kinases as critical targets for anti-cancer drug development.
Main Methods:
- Analysis of genetic alterations in human tumors.
- Investigation of kinase signaling pathways in cancer cells.
- Review of literature on kinase mutations and their functional consequences.
Main Results:
- Kinases, including tyrosine and serine/threonine kinases, are frequently mutated or activated in various human malignancies.
- Activated kinases promote cell proliferation and inhibit apoptosis by influencing transcription factors and cell cycle regulators.
- Specific examples of mutated kinases include EGFR, PDGFR, Src, Abl, Raf, Akt, and Tpl-2.
Conclusions:
- Kinases play a central role in oncogenesis by transducing critical signals for cancer cell growth and survival.
- The aberrant activation of kinases in cancer makes them promising targets for novel anti-cancer therapies.