Experimental Approach Could Treat Deadly Nerve Tumors
Author: Laurie Toich, Associate Editor
There have been significant, groundbreaking advances made against cancer over the past few years, including the emergence of gene therapy and immunotherapy. However, there are still many types of cancer that have no treatments, leaving patients with limited options.
Through genomic profiling, the authors of a study published by Cancer Cell were able to find a novel therapy that showed promise in nerve cell tumors that are currently incurable. The researchers profiled both genes and genetic material in malignant peripheral nerve sheath tumors (MPNSTs) and discovered significant characteristics of the cancer.
“This uncovered potential therapeutic targets we did not expect for these untreatable tumors, but our findings also need further study before knowing whether they will be relevant to patient treatment in the clinic,” said lead author Q. Richard Lu, PhD.
The analysis revealed that the Lats1/2 gene suppresses cancer. The loss of Lats1/2 expression was observed to reprogram the cell so they proliferate and become cancerous. The loss of Lats1/2 also resulted in other genes involved with the HIPPO signaling pathway to become hyperactive, according to the study.
The hyperactive genes, along with associated proteins TAZ and YAP, were observed to work with the TEAD1 protein to activate cancer programs that lead to MPNSTs, according to the study. When overactive TAZ-YAP was blocked in mice models without Lats1/2, the researchers found that signaling from the platelet-derived growth factor receptor was also inhibited.
This approach reduced the size and number of MPNSTs in mice and stopped the growth of human MPNST cells in cultures, according to the study. In future studies, the authors plan to identify small-molecule drugs that will inhibit TAZ-YAP and the cancer programs they activate in order to prevent MPNSTs.
MPNSTs develop in the Schwann cells that form the myelin sheath. Approximately half of MPNSTs are linked to NF1 gene mutations, while the causes of the other cases are unknown. A small number of cases are linked to cancer radiotherapy, according to the study.
The authors noted that NF1 normally balances cell growth rate, but when it mutates, the gene causes benign tumors on the peripheral nerves. Certain patients develop runaway cell growth, resulting in large tumors that can become MPNSTs, according to the study.
MPNSTs are particularly aggressive and resistant to chemotherapy and radiation. These findings suggest that blocking overactive proteins may result in a viable treatment option for patients with MPNSTs who often have a high rate of relapse and a poor prognosis, the authors concluded.