University of Geneva LogoAccording to a latest research, blocking the supposed Hedgehog-GLI (HH-GLI) pathway could perhaps prevent the growth of tumors, metastatic lesions and cancer stem cells. These cancer stem cells are believed to be positioned at the root of cancer growth.

A Geneva-based research team has discovered a method to block the growth of human colon cancer cells. Apparently, this method prevents the disease from reaching higher stages of liver metastasis. Colon cancer usually starts in a treatable form when it is restricted to the bowel wall. However in many cases it might lead to an incurable metastatic stage.

They have revealed the important role played by HH-GLI in the development of colon cancer to these late and incurable stages. HH-GLI is known to be a signaling pathway utilized by cells in order to communicate with each other. Also, they are usually used to determine position, growth and survival.

“Previous works hinted at the possible role of HH-GLI in colon cancer, but this was denied by other studies, so its involvement was never entirely clear,” says lead researcher Professor Ariel Ruiz I Altaba of Geneva University.

Ruiz further added, “In this study we have proven that HH-GLI is essential for the development and growth of colon cancers. The research demonstrates the active presence of HH-GLI signaling in epithelial cells of colon cancers. Moreover, we find that metastatic tumors rely on this pathway for sustained growth. This identifies HH-GLI as a target for novel anti-cancer therapies against so far incurable forms of colon cancer in distant organs, such as the liver.”

With the help of these genetic or pharmacologic methods to block HH-GLI activity, these methods could also prevent cancer stem cell self-renewal. The research team demonstrated the fundamental role of this pathway for the maintenance and survival of cancer stem cells. They showed this by using a novel in vivo analysis in order to examine the participation of cancer stem cells in a growing tumor.

Ruiz I Altaba elucidated that, “Recurrence is a major problem in cancer treatment. Even after a patient has displayed an apparent complete recovery from a primary tumor, recurrence at nearby or distal locations has a poor prognosis.”

“While monitoring recovering mice we noted that tumors began to recur in all cases except for those treated with Cyclopamine for a short period of time after tumor disappearance. The treated mice were kept for up to one year after the treatment and remained healthy and tumor free,” he continues.

Supposedly, this research unlocks the possibility of new anti-cancer therapies which may particularly be used for RNA interference and Cyclopamine. Cyclopamine is believed to be a plant product which is recognized to block Hedgehog pathway activity.

“This work firmly establishes the critical action of HH-GLI in human colon cancer cells, providing the platform for preclinical and future clinical work,” concludes Ruiz I Altaba.

He claimed that, “The finding that a blockade of HH-GLI for a relatively short period was sufficient to eliminate the tumor and prevent recurrence, without negatively affecting the health of the mice, opens the possibility for the use of a therapeutic window to eradicate the tumor without major side effects.”

The research claims that this and other similar molecules may perhaps at present be considered for future research. These molecules could be used in treating terminal patients with metastatic disease and to fight resurgent forms of the disease.

The findings of the research have been published in EMBO Molecular Medicine.