A non-coding RNA axis guides TGF-β-induced gemcitabine chemoresistance

The American Cancer Society estimates 79,030 new cases and 16,870 deaths from urinary bladder cancer (UBC) in the United States this year (1). UBC is prevalent in males and in fact is the 4^th most common cancer types in males (1). Besides sex, age is another risk factor for UBC with about 90% of cases reported in the age group of 55 and above. Depending on the stage of presentation, current treatment options for UBC patients include surgery, intravesical therapy, chemotherapy, radiation therapy and immunotherapy (2,3). Chemotherapy is inevitable for advanced-staged UBC patients besides being used as a neoadjuvant or adjuvant therapy in combination with surgery and radiation therapy. However, the most common drawback of chemotherapy in UBC patients is that it often leads to tumor relapse and recurrence. While numerous reasons can be attributed to such undesirable outcomes, the concept that a small fraction of tumor cells with cancer stem cell (CSC)-like properties are able to survive the harsh chemotherapeutic regimens and able to repopulate as drug resistant tumors has been around for nearly two decades (4,5). However, therapies aimed at eradicating CSCs as an effective therapeutic strategy are not available and remains as a key focus of cancer research.