Meenakshi Anurag, Assistant Professor at Baylor College of Medicine, shared on LinkedIn:
“Proud to share Anurag Lab’s first multidisciplinary study.
Triple-negative breast cancer is a master of the backup plan. Missing a copy of key DNA-repair gene, these tumors lean on a ‘spare’ repair system and survive chemo – so we found a way to take out the spare, too. Now out in Molecular Cancer Therapeutics (American Association for Cancer Research).
In TP53-mutant TNBC, losing one copy of DNA Ligase I (LIG1) drives resistance to chemo, especially platinum. We showed why – and how to exploit it:
- LIG1 loss rewires DNA repair, creating a targetable weak spot
- PARP inhibitors alone: only modest activity
- PARP + ATR inhibitors – drugs already in the clinic – shrank tumors better in preclinical models
- LIG1 status works as a potential biomarker to select the right patients for this combinatorial therapy
Take-home: the very trait that helps these tumors escape chemo becomes their Achilles’ heel – a rational combination of existing drugs, ready to test in clinical trials.
Congratulations to first author Anh M Tran Huynh, who drove this from computational analytics to preclinical validation, and to our collaborators specially, Matthew Ellis (mentor), Christopher Lord, and Jonathan Lei.
With gratitude to our patient advocacy partners GRASP Cancer, Janice Cowden, Josh Newby, whose voices keep this work grounded in what matters most. This one is dedicated to Marlena Murphy.
Baylor College of Medicine feature.”
Title: LIG1 Loss in TP53-mutant Triple Negative Breast Cancer Rewires DNA Repair and Confers Sensitivity to PARP-ATR Inhibitor Combinations
Authors: Anh Minh Tran Huynh, Jonathan T. Lei, Rachel Brough, Christina Sallas, Jun Xu, Jacob B. Pilcher, Xuxu Gou, Junkai Wang, Lacey E. Dobrolecki, Diana M. Fandino, Mariah J. Berner, Allison Greer, Fei Fei Song, Sarah Latka, Hugo Villanueva, Sumimasa Arimura, Sufeng Mao, Zhongqiu Guo, Sofía I. Aramburu, Anran Chen, Thanh Nguyen, Carolina Gutierrez, Dolores H. Lopez-Terrada, Bora Lim, Susan G. Hilsenbeck, Michael T. Lewis, George Miles, Jason C. Mills, Gloria V. Echeverria, Stephen J. Pettitt, Simon N. Powell, Susan M. Rosenberg, Andrew N. J. Tutt, Christopher J. Lord, Matthew J. Ellis, Meenakshi Anurag
Read the full article.
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