Scientists have discovered a new compound that shows promise for treating deadly skin cancers like melanoma that are resistant or unresponsive to leading therapies today.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 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 was shown to inhibit melanoma cell growth, said scientists from Sanford Burnham Prebys Medical Discovery Institute (SBP).
"The unique target of SBI-756 makes it especially promising for use in combination therapy," said Ze'ev Ronai, senior author and scientific director of SBP's La Jolla campus in California.A major issue limiting the effectiveness of current melanoma therapies is that tumours become resistant to treatment."Combining drugs that come at a melanoma from different angles may help overcome the problem of drug resistance,” Ronai added.About 50 percent of melanomas are caused by mutations in a specific gene called BRAF.
The team found that if SBI-756 is co-administered with vemurafenib, a BRAF inhibitor, the tumours disappeared and most importantly, they did not reoccur.Even in mice with advanced/late stage skin 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."The ability of this compound to delay or eliminate the formation of resistant melanomas is very exciting," Ronai added.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 paper was published in the journal Cancer Research.