Melanoma is the leading cause of skin cancer-related death in the U.S., killing one person every hour. Part of the reason for this high mortality rate is the difficulty in distinguishing benign skin moles from malignant melanomas. Continue reading “Towards a more sensitive and specific diagnostic test for melanoma”
A new drug discovered by scientists at Sanford Burnham Prebys Medical Discovery Institute (SBP) may show promise for treating skin cancers that are resistant or unresponsive to today’s leading therapies.
In the United States, 5 million people are treated annually for skin cancer, and 9,000 people die from the deadliest form—melanoma—according to the US Department of Health and Human Services.
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.
In other forms of melanoma, caused by mutations in the genes NRAS and NF1—which are known as unresponsive to BRAF drugs—administering SBI-756 alone significantly 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 tumors disappear.
Drugs that target the translation initiation complex have been intensely pursued in the past few years, not just for melanoma, but for a wide array of cancers. SBI-756 is considered a first-in-class drug because it is the first successful attempt to target a specific part of the complex called eIF4G1.
In fact, SBI-756 is the culmination of seven years of work in Ronai’s group—testing and tweaking the drug’s features to help it bind to the target more readily and to make it easier to formulate. The resulting compound is a significant improvement over the initial version.
“It appears that the dose we need to administer is very low. Even in the experiments where the drug was administered to mice with tumors over a significant period of time, we have not found any toxicity,” Ronai said.
“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, a world renowned leader in the field of protein translation.
“We hope that we’re going to come up with the next generation of the compound that can go into clinical trials—first in melanoma but likely in other tumors,” Ronai said.
The study was performed in collaboration with the Conrad Prebys Center for Chemical Genomics at SBP, Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, McGill University (Canada), the National Cancer Institute, MD Anderson Cancer Center, and Yale University.
A new collaborative study led by researchers at Sanford-Burnham, published today in Cell Reports, provides new insight into the molecular changes that lead to resistance to a commonly prescribed group of drugs called BRAF inhibitors. The findings suggest that targeting newly discovered pathways could be an effective approach to improving the clinical outcome of patients with BRAF inhibitor-resistant melanoma tumors. Continue reading “Sanford-Burnham researchers identify a new target for treating drug-resistant melanoma”
Pedal the Cause, the nonprofit organization dedicated to raising funds for cancer research, recently announced the funding awards for collaborative translational research projects for scientists at Sanford-Burnham, UC San Diego (Moores Cancer Center), and the Salk Institute. This means that scientists from these organizations will join together and embark on projects centered on what occurs “from bench to bedside” in the development of new drug treatment options for patients. Continue reading “The science behind the Pedal the Cause cancer research awards”
Melanoma is the most deadly form of skin cancer with approximately 10,000 deaths per year in the U.S. and more than 65,000 worldwide. Although there are more and better treatment options available today than in previous years, there is still an urgent need to develop drugs that target the numerous pathways melanoma cells use to multiply, spread, and kill. Continue reading “Expanding the options to treat melanoma”
Pedal the Cause San Diego announced four new research projects to be funded from the proceeds of the second annual event at a press conference held at UC San Diego Moores Cancer Center on Friday, March 13. The check presentation, made by Pedal the Cause President and CEO Jim Woodman, drew an excited crowd of former riders, volunteers, sponsors, and cancer advocates eager to find out how their support for this year’s ride will lead to new high-risk, high-reward cancer research. Continue reading “Pedal the Cause announces new grants to advance cancer research”
Researchers at Sanford-Burnham have discovered that without a source of glutamine—one of the 20 amino acids used to build proteins—melanoma cells will stop proliferating and die. Their craving for glutamine stems from their ability to “abuse” this essential nutrient by using it as an additional source of carbon and energy. The findings present a rational basis for a treatment strategy that limits the supply of glutamine to tumors, potentially through nutritional interventions or inhibitors of glutamine uptake. The results of the study appear online in Oncotarget today. Continue reading “Melanoma’s addiction to glutamine is the basis for cancer growth”