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Novartis’ Farydak was approved by the FDA to treat multiple myeloma in 2015. Now scientists in Australia believe the drug can be combined with an early-phase clinical agent to tackle neuroblastoma, a type of nerve tissue cancer mostly seen in young children.
Professor Murray Norris and his colleagues at the Children’s Cancer Institute Australia for Medical Research tested Farydak in combination with an investigational drug called CBL0137 in a mouse model of neuroblastoma. In mice that received the cocktail, “the tumors disappeared and never came back during the entire experiment, whereas the tumors continued to grow in mice that received either no treatment or only single drug treatment,” said Norris in a statement. He presented the findings at the 30th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Dublin.
The two drugs offer two different mechanisms: One launches a direct attack on the cancer cells’ ability to repair their DNA, and the other induces a robust immune response, explained Norris. The results are particularly encouraging because the combo was more effective than any other chemotherapy combinations the lab has tested in aggressive neuroblastoma, he added.
Farydak belongs to a family of drugs called histone deacetylase (HDAC) inhibitors. By blocking HDAC enzymes in multiple myeloma, the drug switches on genes that suppress cancer cells growth and lead to their death.
CBL0137, which is known as a curaxin, works by binding to the Facilitates Chromatin Transcription (FACT) complex often found in tumor cells but not in normal cells. That leads to the dual inhibition of NF-kB—a protein complex that plays a key role in immune response and has been linked to cancer—and Heat Shock Factor 1 (HSF1). It also activates the tumor-suppressing p53 gene.
“Unlike conventional chemotherapy drugs that interact with DNA, CBL0137 is non-DNA damaging and therefore is comparatively less toxic,” said Norris.
Incuron, a joint venture Cleveland BioLabs bowed out of in 2015, now owns CBL0137, which is currently in phase 1 trials in solid tumors and lymphomas. A phase 1 clinical trial CBL0137 alone in children with neuroblastoma is now planned for 2019.
RELATED: Using Zika virus to treat neuroblastoma in children
Other scientists are also exploring novel ways to treat neuroblastoma. Researchers at Nemours Children’s Hospital and the University of Central Florida have suggested that Zika virus’ ability to infect immature nerve cells could also be utilized to kill neuroblastoma. And New York-based Y-mAbs Therapeutics, which recently went public in a $96 million IPO, is developing naxitamab as a first-line treatment for neuroblastoma. The drug targets GD2, an antigen on the surface of cancer cells that has emerged as a promising therapeutic target.
As Norris sees it, because CBL0137-Farydak combo can activate an immune response, it may “significantly boost the efficacy of immunotherapy drugs that are otherwise ineffective for neuroblastoma.” The team is following that logic, testing the combo along with immuno-oncology drugs in mice.
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