
Glioblastoma multiforme (GBM; grade IV astrocytoma) is the most prevalent and aggressive adult primary brain tumour. Standard of care includes surgery, radiotherapy and adjuvant cytotoxic therapy temozolomide (TMZ), conferring a median survival me of 14.6 months. The therapeutic benefit of TMZ depends on its ability to damage DNA and trigger the death of tumour cells. Although TMZ offers some hope to GBM patients, a best 5- year survival rate of 9.8% is achieved.
A key limitation of TMZ is the repair of TMZ-induced DNA damage by the DNA damage repair protein methylguanine-DNA methyl transferase (MGMT) or by deficient mismatch repair (MMR) which are associated with inherent and acquired resistance to TMZ treatment. This not only limits effective therapy in the majority of GBM patients (~47%) but also restricts TMZ’s utility to a very small number of other tumour-types.
University of Nottingham researchers have enhanced this, by synthesised three novel N3-propargyl, C8-substuted TMZ analogues which overcome MGMT+/MMR resistance and possess in vitro an-tumour activity superior to TMZ in GBM and colorectal carcinoma (CRC) cell lines. DMPK package expected autumn 2017.
Necessary cookies are absolutely essential for the website to function properly. This category only includes cookies that ensures basic functionalities and security features of the website. These cookies do not store any personal information.
Any cookies that may not be particularly necessary for the website to function and is used specifically to collect user personal data via analytics, ads, other embedded contents are termed as non-necessary cookies. It is mandatory to procure user consent prior to running these cookies on your website.