Washington | Scientists have discovered a new drug that shows promise for treating deadly forms of skin cancer, such as melanoma, which are resistant to existing therapies. The new compound, named SBI 756, targets a specific molecular machine known as the translation initiation complex. These structures are in every cell and play the critical role of translating messenger RNA (mRNA) into proteins.
In cancer cells the complex is impaired, producing extra protein and providing a growth advantage to tumours. SBI 756 causes the translation complex to dissociate, and inhibit melanoma cell growth. A major issue limiting the effectiveness of current melanoma therapies is that tumours become resistant to treatment, said Ze’ev Ronai from Sanford Burnham Prebys Medical Discovery Institute in US. Combining drugs that come at a melanoma from different angles may help overcome the problem of drug resistance, said Ronai.
About 50 per cent of melanomas are caused by mutations in a specific gene called BRAF. Patients with these tumours are commonly prescribed vemurafenib, a BRAF inhibitor that shrinks tumours. However, many patients experience a relapse within weeks, months, or even years because tumours evolve and become resistant to the drug. A similar phenomenon is seen in mice, where treatment of BRAF melanomas results in an initial response, but 3-4 weeks later the tumours return.
The team found that if SBI 756 is co-administered with vemurafenib, the tumours disappeared and did not reoccur. Even in mice with advanced or late stage BRAF driven cancer, the reappearance of resistant tumours was slowed by including SBI 756. These data suggests that SBI 756 provides a significant advantage in overcoming tumour resistance. In other forms of melanoma, caused by mutations in the genes NRAS and NFI, which are known as unresponsive to BRAF drugs, administering SBI 756 alone significantly lessened the tumour load, the scientists found.
The team is now testing whether combining SBI 756 with existing drugs used for treating these types of melanomas can make the tumours disappear. The finding of SBI 756 is also exciting for the possible treatment of diseases other than cancer, such as neurodegenerative diseases, where the activity of the translation initiation complex is reported to be higher, said professor Nahum Sonenberg of McGill University.
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