Researchers in the US have been working on a new anti-cancer drug. The drug will be absorbed through the gut’s lymphatic system, allowing new ways to treat cancer.
A new anti-cancer drug is under development at the University of Michigan. Researchers believe a new method of absorption, through the lymphatic system rather than blood cells, will allow the drug to out-manoeuvre molecular signalling that leads to drug resistance, whilst increasing cancer-fighting ability and reducing side effects.
The study, which was published in the Nature Communications journal, outlined how a novel kinase inhibiter significantly reduced disease, limited toxicity, and prolonged survival in mice with myelofibrosis, a precursor to leukaemia.
How the drug will work
The anti-cancer drug will work by using the lymphatic system as a storage reservoir. Researchers discovered they could optimise drug concentrations to target two molecular signalling pathways responsible for cancer growth simultaneously.
The team then developed an oral medication called LP-182. This medication was able to simultaneously target phosphoinositide 3-kinase (PI3K), and mitogen-activated protein kinase (MAPK), molecular signalling pathways that drive a high percentage of cancers.
Typically, cancer treatment involves a combination of therapies to target separate cancer cell vulnerabilities. As existing anti-cancer drugs circulate through the body and are absorbed and removed by the body at different rates, it is difficult for the right therapeutic balance to be sustained. Attempting to correctly balance each drug at the necessary concentration to be effective can lead to negative side effects. Failure to correctly balance these therapies can cause treatment to become ineffective and can lead to drug resistance according to Brian D Ross PhD, Research Professor of Radiology at the University of Michigan Medical School.
How LP-182 differs from existing anti-cancer drugs
Unlike typical oral anti-cancer drugs, LP-182 was not designed to be rapidly absorbed through the bloodstream. Researchers found that their anti-cancer drug was first absorbed by the lymphatic system of the mice. As the lymphatic system acts as a storage reservoir for the body, it can gradually release the therapy into the body’s circulation, thus keeping drug concentration at an optimal level.
“Within the therapeutic window, we are able to maintain the on-target inhibition of two distinct pathways that are talking to one another,” explained Ross. “This demonstrates the feasibility of delivering anti-cancer agents directly into the lymphatic system, which opens tremendous new opportunity for improving cancer therapeutic outcomes and reducing the side effects of the agents themselves.”
During myelofibrosis, scar tissue forms in the bone marrow, disrupting regular blood cell production. Molecular signalling can become overactive and cause the proliferation of malignant stem cells, enlarged spleen, extensive fibrosis, and bone marrow failure. The disease can spread through the body’s lymphatic tissue and cause cancer metastasis. The findings from Ross and his team may provide new strategies to prevent the spread of cancers.
Ross also added that “because the gut’s lymphatic system harbours over half the body’s immune cells, the study’s results could provide approaches for the treatment of autoimmune disorders and other conditions.”
