TSRI Team Stops Tumor Growth With 'Credit Card' Molecule
A team of scientists at The Scripps Research Institute (TSRI) reported that a previously ‘undruggable’ cancer regulator has been penetrated by a credit-card like molecule.
Just as a locked door yields to a credit card, the team developed KJ-Pyr-9 to get past the defenses of MYC and disrupt its crucial interactions with its binding partner. MYC is a transcriptional factor that controls gene expression. When overexpressed, MYC causes cell proliferation, which is recognized as an important factor in cancer growth. The cancer regulator is implicated in a majority of cancers, including Burkitt’s lymphoma — a pediatric cancer.
Until now, MYC has defied efforts to stop its activity in cancer cells. Jonathan Ross Hart, staff scientist in the Vogt laboratory at TSRI and co-author of the study, described it like a strand of spaghetti. “At room temperature or body temperature, MYC without any binding partners is random and constantly shifting,” he said.
To attack MYC’s structure, the team used a range of specially designed compounds developed by Kim Janda, co-author of the study, Skaggs Scholar, and member of the Skaggs Institute for Chemical Biology at TSRI. One of these, a small molecule labeled KJ-Pyr-9, was able to stop MYC in its tracks. Administration of the molecule led to the death of cells dependent on MYC. Furthermore, mice models with MYC-dependent tumors which received KJ-Pyr-9 showed no tumor growth after 31 days compared to untreated mice, which demonstrated significant tumor growth.
The scientists hope that their work will uncover how the molecule interacts with MYC and how it can be further developed to reach tumor cells. The team published their findings in this week’s edition of the journal Proceedings of the National Academy of Sciences.
TSRI is currently one of the largest independent, non-profit groups in the world focused on biomedical sciences research. The organization recently announced the end of Michael Marletta’s presidency and the appointment of James Paulson, chair of TSRI’s Department of Cell and Molecular Biology, as acting president and CEO.