HOUSTON, AUGUST 21, 2026 ― A first-in-class therapy to target MYC, one of the most sought-after and difficult targets in cancer biology, showed promise in hard-to-treat blood cancers, according to a new preclinical study from The University of Texas MD Anderson Cancer Center published in Blood .
Researchers led by Michael Andreeff, M.D., Ph.D. , professor, and Yuki Nishida, M.D., Ph.D. , assistant professor, both of Leukemia , found that experimental drug GT19630 interrupts a newly discovered cycle between MYC and GSPT1, resulting in strong anti-cancer activity in preclinical models of leukemia , lymphoma and multiple myeloma , including treatment-resistant and TP53-mutated disease.
"For decades, scientists have struggled to develop therapies that successfully block MYC, leading many in the field to describe it as undruggable," Andreeff said. "By identifying a vulnerability in the relationship between MYC and GSPT1, we found a way to eliminate both proteins and disable a pathway many cancers depend on for survival."
How does this therapy successfully target MYC?
One of the most important drivers of cancer growth, the MYC protein is involved in approximately 70% of all human cancers and acts as a master switch, regulating the genes that enable cancer cells to grow, divide and sustain their metabolism. While blocking this protein has been a high priority for cancer research, scientists have been unable to develop a therapy that effectively interferes with MYC.
This study revealed a previously unknown relationship between MYC and GSPT1. MYC helps activate the GSPT1 gene, and GSPT1 helps cancer cells produce MYC proteins, creating what researchers describe as a "feedforward loop" that could be exploited therapeutically.
A new protein degrader drug called GT19630 disrupts the cycle between MYC and GSPT1 by binding to both proteins and marking MYC for disposal using the cell's natural protein recycling system. The treatment simultaneously degrades GSPT1, causing levels of both proteins to drop significantly and demonstrating broader activity than targeting GSPT1 alone.
How effective is this protein degrader against hard-to-treat blood cancers?
Preclinical models of leukemia, lymphoma and multiple myeloma were highly sensitive to GT19630. Notably, the therapy remained effective in cells with TP53 mutations, which often are associated with treatment resistance.
GT19630 may also offer a path to overcome venetoclax resistance in acute myeloid leukemia (AML) . Researchers found that resistant AML cells had increased MYC and GSPT1 levels. In preclinical models, GT19630 restored sensitivity to venetoclax, dramatically prolonging survival – by more than 300% in one model.
Stem-like AML cells, which can survive treatment and contribute to relapse, often contain higher levels of MYC than normal blood-forming stem cells. Using single-cell RNA analysis, researchers also observed elevated MYC levels in TP53-mutant AML stem cells. Their heightened dependence on MYC made the AML cells more sensitive to GT19630, while normal blood-forming stem cells were less affected. This suggests a potential therapeutic window in which the drug may selectively impact some of the most treatment-resistant leukemia cells while limiting damage to healthy bone marrow.
What's next for this approach?
These findings support GT19630 as a potential pathway to target MYC, but future studies are needed to determine if this strategy is safe and effective in patients. Cancers with high MYC activity may be especially vulnerable to this therapy, raising the possibility of using biomarkers to identify patients most likely to respond.
The study's encouraging activity in venetoclax-resistant AML shows significant translational promise, and further research may evaluate GT19630 as a direct treatment for resistant or relapsed AML or in combination with other therapies.
"In addition to direct MYC inhibition, this approach harnesses the cell's own natural processes to eliminate it," Andreeff said. "This concept could help expand the use of protein degraders against challenging targets and inspire new therapeutic strategies for proteins once considered beyond the reach of conventional therapies."
