[The role of oncogenic tyrosine kinases in the cellular response to anticancer therapy].
Oncogenic tyrosine kinases (OTKs) expressed in malignant tumors stimulate cell proliferation, inhibition of apoptosis, and drug resistance. There are at least three mechanisms of response to chemo- and radiotherapy in OTK-positive cells: overexpression of anti-apoptotic proteins (such as Bcl-xL and Bcl-2) and blocking of the activation of pro-apoptotic proteins (such as caspase 3), arrest in the G2/M phase of the cell cycle, and modulation of DNA repair mechanisms. Furthermore, OTKs elevate the level of reactive oxygen species (ROS)-dependent spontaneous DNA damage. The accumulation of mutations in genetic material increases the metastatic potential following further cancer development. Oxidation-damaged DNA bases are repaired primarily via the mechanisms of base excision repair (BER) and nucleotide excision repair (NER). However, during DNA replication, the areas of single-stranded DNA produced by BER and NER can be converted to double-strand breaks (DSBs), which are then repaired via non-homologous end-joining (NHEJ) and homologous recombination repair (HHR) mechanisms. The HHR pathway is activated in OTK-positive cells due to the elevated level of RAD51 protein expression. In addition, RecQ helicases, such as BLM, play a significant role in this process. Understanding the mechanisms activated by OTKs may help in the development of novel therapeutic strategies that use OTKs as a target.
Słupianek
Artur
A
Katedra Mikrobiologii i Immunologii, Temple University School of Medicine, Philadelphia, PA, USA.
Pytel
Dariusz
D
Majsterek
Ireneusz
I
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis*
D000970:Antineoplastic Agents; D011505:Protein-Tyrosine Kinases