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 tumors. SBI-756 causes the translation complex to dissociate, and was shown to inhibit melanoma cell growth in the study, published today in Cancer Research.
“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. “A major issue limiting the effectiveness of current melanoma therapies is that tumors become resistant to treatment. Combining drugs that come at a melanoma from different angles may help overcome the problem of drug resistance.”
About 50% of melanomas are caused by mutations in a specific gene called BRAF. Patients with these tumors are commonly prescribed vemurafenib, a BRAF inhibitor that shrinks tumors. However, many patients experience a relapse within weeks, months, or even years because tumors 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 tumors return.
The team found that if SBI-756 is co-administered with vemurafenib, the tumors disappeared and most importantly, they did not reoccur. Even in mice with advanced/late stage BRAF driven cancer, the reappearance of . These data suggests that SBI-756 provides a significant advantage in overcoming tumor resistance.
“The ability of this compound to delay or eliminate the formation of resistant melanomas is very exciting,” said Ronai.
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.
The paper was published in the journal Cancer Research.