Scientists demonstrate long-sought drug candidate can halt tumor growth

August 11, 2014

It's a trick any cat burglar knows: to open a locked door, slide a credit card past the latch.

Scientists at The Scripps Research Institute (TSRI) tried a similar strategy when they attempted to disrupt the function of MYC, a cancer regulator thought to be "undruggable." The researchers found that a credit card-like molecule they developed somehow moves in and disrupts the critical interactions between MYC and its binding partner.

The research, published the week of August 11 in the journal Proceedings of the National Academy of Sciences, also shows the drug candidate can stop in animal models.

"We finally hit a home run with this—maybe a grand slam," said Kim Janda, co-author of the new study and Ely R. Callaway, Jr. Professor of Chemistry, director of the Worm Institute for Research and Medicine, and Skaggs Scholar and member of the Skaggs Institute for Chemical Biology at TSRI.

MYC is a transcriptional factor, meaning it controls gene expression. When MYC is overexpressed or amplified, the unregulated expression of genes involved in cell proliferation, a key step in cancer growth, follows. MYC is involved in a majority of cancers, including Burkitt's lymphoma, a fast-growing cancer that tends to strike children.

For years, MYC had challenged researchers who sought to disrupt its activity in . Researchers often design drugs by determining the structure of a disease-related molecule then finding weak points to attack to interfere with the molecule's function.

But MYC is different. "At room temperature or body temperature, MYC without any binding partners is random and constantly shifting," said Jonathan Ross Hart, co-author of the study and a staff scientist in the Vogt laboratory at TSRI. "It's like a piece of spaghetti."

So instead of specially designing a compound to target the structure of MYC, the researchers tested a range of compounds from a library developed by Janda, which he terms "," to see if any could disrupt the interactions between MYC and other proteins important in .

One did—a small molecule called KJ-Pyr-9.

To further investigate, the researchers ran additional tests using cell lines and rodent models. The team found that cells that depend on MYC die if treated with KJ-Pyr-9—in fact, a dose of KJ-Pyr-9 made it seem as if MYC was not there at all. In addition, when mice with MYC-dependent tumors received KJ-Pyr-9, the tumors showed no growth after 31 days, compared with significant tumor growth in untreated mice.

Janda hopes further research will reveal exactly how KJ-Pyr-9 interacts with MYC and how the compound can more effectively reach tumor cells.

Explore further: Scientists find genetic mutations linked to salivary gland tumors

More information: An Inhibitor of MYC Identified in a Kröhnke Pyridine Library, PNAS, www.pnas.org/cgi/doi/10.1073/pnas.1319488111

Related Stories

Scientists find genetic mutations linked to salivary gland tumors

July 28, 2014
Research conducted at the Florida campus of The Scripps Research Institute (TSRI) has discovered links between a set of genes known to promote tumor growth and mucoepidermoid carcinoma, an oral cancer that affects the salivary ...

Master regulator of key cancer gene found, offers new drug target

June 25, 2014
A key cancer-causing gene, responsible for up to 20 percent of cancers, may have a weak spot in its armor, according to new research from the Masonic Cancer Center, University of Minnesota.

New findings on neurogenesis in the spinal cord

March 5, 2014
Research from Karolinska Institutet in Sweden suggests that the expression of the so called MYC gene is important and necessary for neurogenesis in the spinal cord. The findings are being published in the journal EMBO Reports.

Scientists identify a critical tumor suppressor for cancer

August 2, 2012
Scientists from the Florida campus of The Scripps Research Institute have identified a protein that impairs the development and maintenance of lymphoma (cancer of the lymph nodes), but is repressed during the initial stages ...

Hard-to-treat Myc-driven cancers may be susceptible to drug already used in clinic

December 14, 2012
Drugs that are used in the clinic to treat some forms of breast and kidney cancer and that work by inhibiting the signaling molecule mTORC1 might have utility in treating some of the more than 15 percent of human cancers ...

Survival protein a potential new target for many cancers

January 7, 2014
Walter and Eliza Hall Institute researchers have discovered a promising strategy for treating cancers that are caused by one of the most common cancer-causing changes in cells.

Recommended for you

Discovery could lead to better results for patients undergoing radiation

July 19, 2017
More than half of cancer patients undergo radiotherapy, in which high doses of radiation are aimed at diseased tissue to kill cancer cells. But due to a phenomenon known as radiation-induced bystander effect (RIBE), in which ...

Definitive genomic study reveals alterations driving most medulloblastoma brain tumors

July 19, 2017
The most comprehensive analysis yet of medulloblastoma has identified genomic changes responsible for more than 75 percent of the brain tumors, including two new suspected cancer genes that were found exclusively in the least ...

Novel CRISPR-Cas9 screening enables discovery of new targets to aid cancer immunotherapy

July 19, 2017
A novel screening method developed by a team at Dana-Farber/Boston Children's Cancer and Blood Disorders Center—using CRISPR-Cas9 genome editing technology to test the function of thousands of tumor genes in mice—has ...

Combining CAR T cells with existing immunotherapies may overcome resistance in glioblastomas

July 19, 2017
Genetically modified "hunter" T cells successfully migrated to and penetrated a deadly type of brain tumor known as glioblastoma (GBM) in a clinical trial of the new therapy, but the cells triggered an immunosuppressive tumor ...

How CD44s gives brain cancer a survival advantage

July 19, 2017
Understanding the mechanisms that give cancer cells the ability to survive and grow opens the possibility of developing improved treatments to control or cure the disease. In the case of glioblastoma multiforme, the deadliest ...

New way found to boost immunity in fight cancer and infections

July 19, 2017
An international research team led by Université de Montréal medical professor Christopher Rudd, director of research in immunology and cell therapy at Maisonneuve-Rosemont Hospital Research Centre, has identified a key ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

Rosser
not rated yet Aug 11, 2014
While this research is great, in that it stops tumor growth in its tracks, the article does not indicate if it actually kills the entire tumor. If the cancer still exists, but isn't growing, it still presents and clear and present danger.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.