National University of Singapore researchers have gone ahead and revisited a drug which they believe can be a problem solver when it comes to acute leukaemia. The drug, which is referred to as PIK-75, was initially discovered around 15 years ago. Since that time, unfortunately, it has been disregarded vis-à-vis new drugs, but that said, the Cancer Science Institute of Singapore at NUS is of the opinion that the drug has in it the ability to fight acute leukaemia, which is a form of blood cancer.
As per the research team, the drug has the capacity to block two important cancer-causing paths that are associated with acute leukaemia thereby enabling it effectively halt the progression of the disease.
The disease affects children predominantly, is aggressive, and progresses in haste, inhibiting stem cells within the bone marrow that create T cells, which are essential in fighting off body infections. Acute leukaemia leads to T cell formation that gets congested and starts affecting the function of its normal counterparts, therefore compromising the body’s immune system. It is seen that many patients who get recovered from paediatric acute leukaemia may relapse and, in some cases, may not even respond to the line therapy.
As per the lead author of the study, Professor Takaomi Sanda, the current strategies of cancer treatment mostly focus on a single molecule that is specific to the disease, just like an oncoprotein. They learned the ability of the cells to increase is due to multiple mechanisms, of which pinpointing and dealing with just one is not going to be sufficient in order to slow the progression of the disease.
The researchers have revealed the underlying pathways, which means that any medical intervention has the ability to destroy the potential path of the disease and halt its spread across the body of the patient. The force that drives the acute laeukemia progression is separated into type A as well as Type B abnormalities where the former happens to be an overexpression of TAL1 oncogenic transcription factor. They happen to be strong proteins that help sustain cancer multiplication and are present in half of all leukaemia cases.
The latter is the activation of signalling pathways that are abnormal, like PI3K-AKT-PTEN. Under this, a cluster of proteins in a cell work together in order to control the cell’s functioning while also promoting the cancer cell’s development. Both of these mechanisms are identified as helping the multiplication of cancer cells within patients.
The researchers went ahead and carried out the screening of the drug in order to identify the candidates so as to treat acute leukaemia. Of the 3000 compounds present, PIK-75 exhibited the best capacity to block TAL1 activity and the PI3K-AKT-PTEN path. Hence, it could thumpingly reduce the cancerous cells’ survivability.
Notably, the research team was surprised to witness that PIK-75 was originally identified as an inhibitor of the pathway around 15 years ago but was consistently regarded as not being in favour of treatments.
Aiming at the mechanism of oncogenic collaboration, they demonstrated the novel therapeutic compound’s efficacy in order to inhibit the core oncogenic machinery, which consists of both type A as well as B abnormalities that drive the progression of leukaemia, as per professor Sanda. A strong cytotoxicity created by PIK-75 against acute leukaemia cells at doses which are low as compared to prior studies with other kinds of drugs which required high concentrations to inhibit the growth.
Because of its ability to hinder both mechanisms, PIK-75 happens to be highly feasible in clinical settings. The scientists are now wanting to develop an analogue that is soluble in the drug so that it can be administered to patients.
As per Dr. Lim Fang Qui, the leader of the study, they are delving deep into the cancer pathogenesis to unfurl more insights that are lifesaving, and they also plan to unearth many novel drugs that can thwart acute leukaemia’s primary oncogenic mechanism.
