Black Sea Journal of Health Science

Yazarlar: Sevgi Uğur MUTLUAY, Leyla Didem KOZACI

Konular:Genel ve Dahili Tıp

DOI:10.19127/bshealthscience.825971

Anahtar Kelimeler:Cancer,Chemotherapy,Signaling pathways,Targeted therapy,Protein kinase inhibitors

Özet: In cancer treatment, conventional chemotherapeutics have been in clinical use since 1940s. Even though their efficacy has been established for many years, selectivity problem and serious side effects limit their use. Disadvantages of available therapies and need for novel anti-cancer drugs induced a shift in research towards that direction. Over the past 20 years, by shedding light on molecular mechanisms of cancer, intracellular proteins, that might be targets for new drugs, have been defined. Of these targets, primary ones are; PI3K/Akt/mTOR, Ras/Raf/MEK/ERK, Ubiquitin-Proteasom and Hedgehog pathways. These pathways and their downstream effectors shown to play a role in many cancer types. Protein kinases, which are involved in intracellular signaling pathways and found to be related to those pathways, are the molecules that are most studied. Many inhibitor molecules and/or monoclonal antibodies spesific to tyrosine and serine/theronine kinases have been developed and brought into use. Several members of tyrosine kinase family, which consists of around 20 subclasses, have been shown to be related to cancer. In this regard, prominent receptor tyrosine kinases can be sorted as EGFR, PDGFR, VEGFR, FLT3 and ALK. Other protein kinases; Src, BTK, CDK and AMPK have been reported to mediate critical processes in cancer development. Beside those targets, potential molecular targets and chemotherapeutic agents to these targets have been defined. Many molecules, that were developed to inhibit NOTCH, JAK-STAT, Nuclear Factor Kappa B, Wnt/ ß-Catenin pathways, Insulin, FGF, HGF, GSK-3 receptors, Protein Kinase C, Aurora Kinase and Hsp90 activity, are in stage of clinical study.

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