Reported in the journal Nature Communications, the molecule targets a mechanism of tumour development that had previously been considered ‘undruggable’– in other words, extremely difficult, if not impossible, to target with a drug – and could open the door to further promising new candidates.
The cells in our body go through a continuous process of growth, division and death, but when this process goes awry it can lead to uncontrolled cell growth and the development of tumours. Unchecked, this growth first manifests as a localised tumour, but eventually the cancer will ‘metastasise’, invading surrounding tissues and organs. Over nine out of ten cancer deaths are attributable to such progression.
However, even in a sick patient, the vast majority of the body’s 50 trillion cells maintain accurate control over processes like growth and division for a lifetime. This process is orchestrated by proteins known as ‘transcription factors’ that instruct DNA in the cells to produce specific proteins needed by the cell at specific times. A transcription factor searches for specific genes on DNA and once it finds them, turns them on as needed. Common perturbations in cancer, such a mutation in the gene that produces a transcription factor, or an over-production of the factor itself, can disrupt the proper functioning of this network.
Recently, cancer biologists discovered that one particular transcription factor called FOXM1 is vastly over-abundant in many diverse types of cancers including breast, lung, ovarian and head and neck carcinomas. Importantly, the amount of FOXM1 present in a given tumour was shown to correlate with both the stage of the disease and the severity of prognosis, with high levels of FOXM1 indicative of advanced disease and poor patient outcome.
FOXM1 has been shown to control the activity of many gene targets known to play a role in the development and spread of cancer. However, transcription factors have long been considered ‘undruggable’.
Researchers from the Department of Chemistry at the University of Cambridge and the Cancer Research UK Cambridge Institute hypothesized that FOXM1 might represent a novel target for next-generation chemotherapeutics and developed a tool to identify potential ‘small molecules’ that could inhibit the action of the transcription factor – like finding the correct key to fit into switch and deactivate the transcription factor.
Read the full story
Image: Metastatic Breast Cancer in Pleural Fluid
Credit: Ed Uthman
Reproduced courtesy of the University of Cambridge
____________________________________
Drugging the undruggable: discovery opens up possibility of slowing cancer spread
13 November 2014
A trawl through a library of more than 50,000 ‘small molecules’ has identified a potential candidate to inhibit the spread of cancer cells throughout the body.