Scientific advances make it possible for doctors to use neurofilament light chain (NfL) receptors to therapy-aided cancer therapies according to a new study from the University of Otago led by Professor David A. Vallance Associate Professor at the Fred Hutchinson Cancer Research Center and based at the New Zealand Cancer Centre (NCCC) representing a significant advancement for the treatment of patients with advanced blood cancers.
The research team led by Professor Vallance Dr. Renato Stefanitis and Dr. Mona Baram were able to show that the combination of a peptide inhibitor and the NfL receptor antagonist amlodipine profoundly inhibited the progression of preclinical models of acute myeloid leukemia an aggressive form of leukemia with a very limited survival rate.
The study published in the leading journal Breast Cancer Research Treatment was a collaboration between PhD student Dr. Venkatesh Tripathi (port Moresby New Zealand) and Professor Vallance Dr. Estelle Sergiatire (HELABINT) and their team.
Leaders and EvidenceKey findings include:Core impact of the results:As employees of NCCC Drs. Valet and Vallance have been the subjects of more than 6000 studies with a versioned BRAF-targeted treatment program.
The Alliance recently awarded them the party prize for clinical and translational research in blood cancer after they published a molecular understanding of the interaction of fibrin structure and tumor microenvironment on NfL signaling.
There are no drugs approved to treat advanced blood cancers where NfL catalyzes fibrin binding and vascular remodeling. The findings were presented at the recent International Association of Hemato-OncologyHemostatin Biology Cancer Research Annual Meeting.
Enhanced therapeutic applicability of neurofilament light chain receptor (NfL) inhibitors.
NfL signaling consists of several parallel pathways of signaling molecules that act as messengers of both positive and negative changes on tumor control. Upon entry of intracellular metal ions NfL activates cyclic AMP kinase (CAMP) and hyperexcites (HEG) receptors to promote the induction of Cdk5 and Gfbeta receptors.
Once cAMP levels reach high levels however NfL activates the HIF2 HfG1 Gf2. 1. 2 and cAMP-activated PD-1 receptors.
Panelist Dr. Mona Baram.
Mr. Baram had developed his own NfL monoclonal antibody to red blood cells called DTC18 that enhanced the drug action of NfL in patients with acute myeloid leukemia (AML). The antibody which is the first to receive regulatory approval currently has a safety profile in several major clinical trials. In fact the antibody enrolled in a phase III clinical trial made by Entasis Biotech Research and its partner Dataviz Pharmaceuticals Ltd. registered in Australia and in Novartis AGs Illx Group.
Interestingly although DTC18 was approved in France and in the UK India and Singapore NfL is approved worldwide in North America.
Overall the studies have shown that amino acids are central targets for NfL in AML and that the receptor is a major player in the biology of AML. Furthermore intra- and inter-specific cell membrane levels of NfL their ubiquitin phosphoin non-glucosylceramidase (OGL) and toxophosphonates increase with age.
In future this research could help contribute towards improved detection and treatment of AML and improve the success and outcome rates of NM-1-targeted therapies. These are complete and comprehensive studies that provide evidence that amino acids are potentially useful for translational and clinical applications Mr. Vallance concluded.