ROS receptor tyrosine kinase: a new potential target for anticancer drugs.
ROS kinase is one of the last two remaining orphan receptor tyrosine kinases with an as yet unidentified ligand. The normal functions of human ROS kinase in different body tissues have not been fully identified so far. However, the ectopic expression, as well as the production of variable mutant forms of ROS kinase has been reported in a number of cancers, such as glioblastoma multiforme, and non-small cell lung cancer, suggesting a role for ROS kinase in deriving such tumors. It is thought also that c-ROS gene may have a role in some cardiovascular diseases, and the fact that homozygous male mice targeted against c-ROS gene are healthy but infertile, has inspired researchers to think about ROS inhibition as a method for development of new male contraceptives. The recent discovery of new selective and potent inhibitors for ROS kinase, along with the development of new specific diagnostic methods for the detection of ROS fusion proteins, raises the importance of using these selective inhibitors for targeting ROS mutations as a new method for treatment of cancers harboring such genes. This review focuses on the ectopic expression of ROS and its fusion proteins in different cancer types and highlights the importance of targeting these proteins for treatment of substantial cancers. It describes also the recent advances in the field of ROS kinase inhibition, and the potential clinical applications of ROS kinase inhibitors.
El-Deeb
Ibrahim Mustafa
IM
Life/Health Division, Korea Institute of Science and Technology, Cheongryang, Seoul, Republic of Korea; Department of Biomolecular Science, University of Science and Technology, Yuseong-gu, Daejeon, Republic of Korea.
Yoo
Kyung Ho
KH
Lee
So Ha
SH
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002318:Cardiovascular Diseases / Q000201:enzymology; D006801:Humans; D007246:Infertility / Q000235:genetics; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy / Q000201:enzymology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D011519:Proto-Oncogenes; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction
D000970:Antineoplastic Agents; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; C062333:ROS1 protein, human; D020794:Receptor Protein-Tyrosine Kinases