Race Oncology Ltd (ASX:RAC)’s cancer drug Zantrene® continues show a diverse range of benefits.
Researchers from the MD Anderson Cancer Center in Texas have identified additional Zantrene drug combinations with superior efficacy in Acute Myeloid Leukaemia (AML) cells.
The research team was led by Professor Borje Andersson and Associate Professor Ben Valdez of the MD Anderson Cancer Center, with the RAC sponsored study, now published in the Journal Leukemia & Lymphoma under the title 'Enhanced cytotoxicity of bisantrene when combined with venetoclax, panobinostat, decitabine and olaparib in acute myeloid leukemia cells'.
The MD Anderson team identified synergism of Zantrene and venetoclax in combination with panobinostat, decitabine or olaparib, known inhibitors of BCL2, histone deacetylase, DNA methyltransferase and poly (ADP-ribose) polymerase, respectively, in AML cells.
These combinations were found to enhance DNA damage, cleavage of Caspase 3 and PARP1, DNA fragmentation, increased ROS and potent apoptosis activation in AML cells.
Similar results were observed using mononuclear cells isolated from leukaemia patients, but not from healthy donors.
The SAPK/JNK signalling pathway was strongly activated by the combination treatments, whereas the PI3K/mTOR and Wnt/b-catenin pro-survival pathways were inhibited.
Pre-clinical data ahead of Phase 1b/2 trial
“This work provides further preclinical data to support our upcoming Phase 1b/2 extramedullary AML trial in Australian and Europe, where patients will be treated with Zantrene in combination with decitabine or cytarabine,” CHM chief scientific officer Dr Daniel Tillett said.
“We are extremely excited about being able to quickly translate this work from the lab into the clinic, where it has the potential to help AML patients in need.”
About RAC
Race Oncology is a precision oncology company with a Phase 2/3 cancer drug called Zantrene® – a potent inhibitor of the Fatso/Fat mass and obesity associated (FTO) protein. Overexpression of FTO has been shown to be the genetic driver of a diverse range of cancers.
Race is exploring the use of Zantrene as a new therapy for melanoma and clear cell renal cell carcinoma, which are both frequent FTO over-expressing cancers.
In breakthrough preclinical research, Race has also discovered that Zantrene protects from anthracycline-induced heart damage, while in tandem acting with anthracyclines and proteasome inhibitors to improve their ability to target breast cancer. Race is evaluating this discovery.
RAC also has compelling clinical data for Zantrene as a chemotherapeutic agent and is in clinical trial in AML.