Sometimes, genes get stuck together. They fuse to form hybrids, and the result is not good: DNA is discombobulated, abnormal proteins are produced, and cancer can result. One way this can happen is translocation, when a piece of DNA from one chromosome attaches itself to part of another chromosome. 

This can result in translocation renal cell carcinoma (tRCC), a rare and aggressive form of kidney cancer that mainly affects women and young adults. The particular culprits in tRCC are fused transcription factor genes, most commonly TFE3. 

Because this form of cancer is so rare, “optimal systemic treatment strategies remain unclear,” says medical oncologist and Co-Director of the Kidney Cancer Research Program, Yasser Ged, M.B.B.S. “However, in small studies, immunotherapy combinations have shown promise.” 

Ged, along with investigators from Hopkins, Memorial Sloan Kettering Cancer Center, Fox Chase Cancer Center, and City of Hope, recently led a multicenter study of the responses of 22 patients – one of the largest studies of tRCC patients to date – with metastatic TFE3-positive tRCC. These patients received either dual IO therapy or IO in combination with a VEGF (vascular endothelial growth factor) tyrosine kinase inhibitor (TKI), a drug that blocks cancer from making its own supply of blood vessels. 

In the study, published in the Journal of Immunotherapy, patients who had the IO-VEGF-TKI combination treatment had a better response and better disease control, compared to those who received the dual IO therapy. However, the authors note, larger, prospective trials are needed to confirm these findings and guide treatment strategies in this rare population.