Killing Cancer Through Overstimulation

Cancer cells were treated with a control (left) and the overstimulating compound MCB-613 (right). Credit: Lei Wang

Cancer cells were treated with a control (left) and the overstimulating compound MCB-613 (right). Credit: Lei Wang

Cancer requires extensive and fast division in order to become a serious threat, but this feature also renders it vulnerable, allowing certain growth pathways to be targeted. A new drug candidate has emerged which exploits this weakness, overstimulating proteins required for growth - tipping cellular stress in virulent cancer cells over the edge.

"No prior drug has been previously developed or proposed that actually stimulates an oncogene to promote therapy. Our prototype drug works in multiple types of cancers and encourages us that this could be a more general addition to the cancer drug arsenal."

Many types of cancer require specific mutations in genes related to growth, and one particular target is the steroid receptor coactivator (SRC) family of oncogenes. These lie at the centre of signalling pathways used to grow rapidly, and conventional research has focused on inhibiting them to prevent tumour growth. Instead of inhibiting, this new strategy aims to upregulate their activity, overstimulating them to an extent that destroys the host cell. In their search for a suitable molecule which might cause such stimulation, researchers stumbled across a compound labeled MCB-613. 

'This compound killed human breast, prostate, lung, and liver cancer cells, while sparing normal cells. When the researchers administered MCB-613 to 13 mice with breast cancer, the drug candidate almost completely eliminated tumor growth without causing toxicity, whereas tumors continued to grow by about 3-fold over 7 weeks in the control group of 14 mice'

MCB-613 works by accumulating unfolded proteins in the endoplasmic reticulum of a cell, which builds and folds proteins correctly. This overstimulation makes the workload too much for the structure to handle, leading to a toxic build up. This then triggers a cell stress response which was able to kill many types of cancer cells in the research. 

While this method might not work in every type and is merely one addition in an ever increasing arsenal against cancer, if research hones and improves it, it could become a potent weapon against particularly virulent varieties. 

Read more at EurekAlert