Acknowledgments to Shanghai Collaborative Innovation Center for Translational Medicine and L. Zheng (Children’s National Medical Center)

A groundbreaking study published in Nature Communications on May 7, 2026, has uncovered a novel mechanism by which non-small-cell lung cancer (NSCLC) evades targeted therapies, potentially paving the way for more effective cancer treatments. Researchers from Shanghai Jiao Tong University and other institutions have identified a noncanonical glucose metabolic pathway, facilitated by the glucose transporter GLUT6, that enables cancer cells to resist EGFR and KRAS inhibitors—two widely used targeted therapies for lung cancer.

A New Pathway to Therapy Resistance

The study reveals that GLUT6 drives glucose into cancer cells and redirects it toward the production of methylglyoxal, a compound that activates the NRF2 pathway. This pathway is known for its role in protecting cells from oxidative stress and promoting survival, thereby conferring resistance to targeted cancer therapies. The research also found that GLUT6 expression is upregulated by therapy-induced activation of the transcription factor MAZ, creating a feedback loop that sustains resistance.

Clinical and Translational Implications

The findings hold significant promise for overcoming resistance in lung cancer treatment. By targeting GLUT6, researchers suggest it may be possible to prevent and reverse resistance to EGFR and KRAS inhibitors, two cornerstones of NSCLC therapy. The study highlights the importance of GLUT6 as a potential therapeutic target, offering a new strategy to revitalize glucose metabolism–based anticancer approaches.

the MAZ–GLUT6–NRF2 axis identified in the study correlates with clinical treatment response and relapse, providing a biomarker for predicting patient outcomes and tailoring personalized treatment plans.

Multidisciplinary Collaboration and Support

The research was supported by the Shanghai Collaborative Innovation Center for Translational Medicine and involved collaboration with L. Zheng from Children’s National Medical Center. Funding was provided by the National Natural Science Foundation of China and the Shanghai Municipal Science Foundation, underscoring the multidisciplinary and international effort behind this discovery.

Revitalizing Cancer Metabolism Research

This study not only sheds light on the metabolic adaptability of cancer cells but also opens new avenues for developing combination therapies that target both the primary tumor and its metabolic resistance mechanisms. By focusing on GLUT6, scientists may be able to disrupt the metabolic rewiring that allows cancer cells to survive and thrive despite targeted treatments.

As the scientific community continues to explore these findings, the potential for improved outcomes in lung cancer patients—and possibly other cancers with similar metabolic adaptations—becomes increasingly tangible.

Source: Nature Communications, "GLUT6-facilitated noncanonical glucose metabolic rewiring enables resistance to targeted cancer therapy," May 7, 2026.