The Faltas Lab at Weill Cornell Medicine has made pivotal discoveries in understanding the molecular mechanisms driving bladder cancer. Our latest research, published in Nature, was spearheaded by Dr. Bishoy Faltas, along with key contributions from Duy Nguyen (now a doctoral student at Harvard Medical School), Dr. Weisi Liu, an instructor in our lab, and bioinformatics expert William Hooper from the New York Genome Center. Together, they identified that the antiviral APOBEC3 enzymes initiate early DNA mutations in bladder cancer, marking them as critical promoters of the disease. Additionally, we uncovered that chemotherapy, particularly platinum-based agents like cisplatin, induces further waves of mutations, which help the cancer evade treatment.
Another key finding, led by our lab team, was the discovery of extra-chromosomal DNA (ecDNA) structures in tumor cells, which contain multiple copies of oncogenes like CCND1. This breakthrough revealed how these ecDNAs drive both cancer growth and resistance to therapy. Moving forward, our lab is focused on targeting these ecDNAs and exploring therapies like HER2 inhibitors in patients whose tumors show strong ERBB2 ecDNA signatures.
The work was made possible through close collaboration with Dr. Olivier Elemento and Dr. Nicolas Robine, and it paves the way for new precision medicine strategies to tackle advanced bladder cancer.
This article was highlighted on the cover of the November 7th, 2024 article.