Two new studies led by researchers from Yale have discovered new information about the ALK receptor (anaplastic lymphoma kinase molecule) and the role it plays in cancer formation. The studies have made progress in determining ALK’s structure status as a receptor protein. Their findings were published in “Nature.”
The codirector of the Cancer Biology Institute, Joseph Schlessinger, is a senior author of one of the studies. Yale School of Medicine assistant professor of pharmacology Daryl Klein is the senior author of the second study.
A postdoctoral associate in Klein’s laboratory, Tongqing Li, stated that ALK was one of the receptor tyrosine kinases whose activation led to carcinogenesis. ALK receptors are primarily located in the central nervous system and the brain.
Similar to other receptors, ALK received signals from other parts of the body to complete different actions or synthesize new proteins. The receptor’s activation is dependent on the attachment of the ligand and a process known as dimerization. Dimerization refers to the process through which receptors are internalized in cells.
In an email, Schlessinger wrote that ALK was initially discovered as an oncogenic fusion protein, explaining that roughly 20 different partners of oncogenic ALK-fusion proteins were found to be key drivers of various cancers. These include inflammatory myofibroblastic tumors, B-cell lymphomas and pediatric neuroblastoma.
The researchers found that ALK receptor dimerization was associated with the development of the aforementioned cancers, adding that the disease could occur through mutations in cells in nervous tissue.
In addition to this, the interchange of chromosome parts can also trigger ALK tyrosine kinase activity, causing the development of these cancers. The researchers note that their discoveries on the structure of this particular receptor can be used to better understand the mechanisms behind receptor tyrosine kinase activation. This may, in turn, be useful to pharmaceutical companies because it will facilitate the development of new ALK inhibitor medications that hinder the activation of said receptors and offer treatment for a variety of cancers.
Klein believes that these treatments could be used to treat illnesses such as neuroblastoma, which is a common pediatric cancer that makes up about 12% of childhood cancer mortality.
The researchers are now focused on conducting research to find a combination that could effectively disable the activation complex of the anaplastic lymphoma kinase molecule.
The lab work was carried out at Schlessinger’s and Klein’s laboratories at the Yale School of Medicine, with contributions being made by the Structural Biology Department at St. Jude Children’s Research Hospital.
These two studies are likely to shed more light on brain cancers and how they develop, and such information would be a valuable addition to the work being done by various biotech companies such as CNS Pharmaceuticals Inc. (NASDAQ: CNSP) that are looking to commercialize more effective treatments for primary brain cancers.
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