Genetics Reveal Most Effective Multiple Myeloma Treatment

A recent study found that the gene tight junction protein 1 (TJP1) could help physicians determine which treatment would be most effective for patients with multiple myeloma.

"Proteasome inhibitors form the cornerstone of our standard therapy for multiple myeloma. However, no biomarkers have been clinically validated that can identify patients most likely to respond to this treatment," said study lead author Robert Orlowski, MD, PhD. "Our findings provide a rationale for use of TJP1 as the first biomarker to select patients who are most and least likely to benefit from proteasome inhibitors."

According to the study, published by Cancer Cell, TJP1 modulated signaling through a pathway that involved EGFR, JAK1, and STAT3, which showed plasma cells expressing low levels of TJP1 have high EGFR/JAK1//STAT3 activity and proteasome content.

"Therefore, these plasma cells were resistant to proteasome inhibitors," Dr. Orlowski said. "Moreover, they demonstrated a previously unknown role for EGFR signaling in myeloma, and for STAT3 in controlling the level of proteasomes in cells, and therefore the cell's ability to break down proteins.”

The researchers found that patients with myeloma cells that expressed low TJP1 were less likely to respond to treatment with bortezomib.

"This study allows us to identify promising future directions to overcome proteasome inhibitor resistance in patients with high signaling through EGFR/JAK1/STAT3 pathway by offering combination therapies such as bortezomib with either the EGFR inhibitor erlotinib, or a JAK1 inhibitor such as ruxolitinib," Dr. Orlowski concluded.