Reigniting cell death
Scientists at the Walter and Eliza Hall Institute in Melbourne and their collaborators at Genentech have tailor made a new chemical compound that blocks a protein that is linked to poor responses to treatment in cancer patients.
The compound, WEHI-539, binds and blocks the function of the B-cell lymphoma-extra large (BCL-XL) protein. BCL-XL is a member of the BCL-2 family of proteins and acts as a pro-survival protein by preventing the release of the pro-apoptotic factor, cytochrome c, from mitochondria.
A critical factor in cancer growth is the development of this ability to bypass cell death. One way tumours do this is by overexpressing the BCL-XL protein, which renders malignant tumour cells resistant to anticancer treatments.
High levels of BCL-XL are also associated with poorer outcomes for patients with lung, stomach, colon and pancreatic cancer.
This ability to prevent cells from dying makes BCL-XL an attractive target for drug development - inhibiting BCL-XL can restore cell death and make cancer cells responsive to treatment.
WEHI-539 was developed from scratch using the three-dimensional structure of BCL-XL to build and refine its design. It is not optimised for use in patients, but will be used as a tool for researchers to further understand how BCL-XL controls cancer cell survival.
Instead of inhibiting multiple members of the prosurvival BCL-2 family, the researchers propose that selectively inhibiting BCL-XL will minimise toxicity and thus reduce side effects in patients.
WEHI-539 belongs to a class of chemicals called ‘BH3-mimetics’, which all bind to the same region of BCL-XL or related proteins. Two BH3-mimetics, called navitoclax (ABT-263) and ABT-199/GDC-0199, are currently in clinical trials for the treatment of cancer, particularly leukaemia and lymphoma.
The research was recently published in Nature Chemical Biology.
How brain cells are affected by Tourette syndrome
US researchers have conducted a cell-by-cell analysis of brain tissue from individuals with...
Preventing neural graft rejection in Parkinson's patients
Researchers have engineered a way to fool the immune system into accepting neural grafts as part...
Retinal health linked to dementia risk, study shows
Researchers have discovered that the blood vessels at the back of the eye — called retinal...
