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t m c » p u l s e | o c t o b e r 2 0 1 8 34 Solutions: TMC Innovations Connecting the Warburg Pathway to Cancer Growth Solving a 100-year-old mystery points to potential breast cancer therapies B y C h r i s t i n e H a l l A rmed with new insights about the way cancer cells fuel their growth, Baylor College of Medicine researchers are working with col- leagues in New York to explore new possibilities for cancer treatment, particularly breast cancer. Their work solved a century-old mystery about the Warburg path- way—a process most cancer cells use to generate energy via glucose fermentation. Bert O'Malley, M.D., a founding father in the field of molecular endo- crinology and the longtime chair and professor of Baylor's depart- ment of molecular and cellular biol- ogy, is leading the team. Members include researchers from Roswell Park Comprehensive Cancer Center in Buffalo, New York. The team discovered a connec- tion between PFKFB4, an enzyme in the Warburg pathway, and the glu- cose-driven activation of a protein called SRC-3. SRC-3 (steroid receptor coactiva- tor-3) was identified as an important regulator of gene expression years ago in O'Malley's laboratory. Once sparked by PFKFB4, the protein becomes an oncogene—a gene that can cause cancer and its rapid growth and metastasis. "We knew SRC-3 was the key to cancer growth, and we knew what could affect SRC-3, but we didn't know sugar could," said O'Malley, now chancellor of Baylor College of Medicine. "In fact, nobody knew the Warburg pathway did anything to the oncogene or that the enzyme could activate the protein." Meet Otto Warburg The Warburg effect is named for Otto Warburg, M.D., Ph.D., a German Bert O'Malley, M.D., considered a founding father in the field of molecular endocrinology, sits for a portrait in his office. O'Malley, chancellor of Baylor College of Medicine, was awarded the National Medal of Science in 2007.