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Endocan: A Breakthrough Target for Glioblastoma Treatment

Endocan, a tumor-secreted protein, drives glioblastoma progression and therapy resistance. Targeting it may revolutionize treatment and improve survival.

by Dr. Preethi Balasubramanian on January 10, 2025 at 3:00 PM

Highlights:

Endocan drives glioblastoma growth and enhances resistance to radiation therapy
Blocking endocan-PDGFRA interaction improves treatment outcomes
Targeting endocan could provide indirect cMyc inhibition, a pivotal cancer protein

Glioblastoma is a highly malignant and fatal primary brain tumour which still poses a significant problem in oncology. The patients that receive diagnosis for this kind of tumor have a limited life expectancy of 12 to 15 months and 5% of them only make it to the five year mark. Conventional therapies such as radiation pale in their effectiveness, mainly due to the aggressive biological behavior of the tumor (1^✔).

A research, in which UCLA scientists also took part, has recently revealed a potential strategy based on a new protein, endocan, that may improve existing treatments for the disease. The study, reported in the journal Nature Communications, describes the various ways in which the blood vessels and the tumour communicate and the role that such communication plays in glioblastoma progression and invulnerable to treatment.

‘Did You Know?
Glioblastoma's aggressive edge regions resist treatment, but targeting endocan could change that. #cancer #oncology’

Endocan, a protein that is released by the endothelial cells of blood vessels; it is involved in the progression of glioblastoma by activating the PDGFRA receptor on the cell surface of the tumor cells. This receptor is known to stimulate tumor proliferation and also enhance radio-resistance in glioblastoma.

Role of Endocan in the Proliferation of Glioblastoma Cells

It was found out that Endocan plays a significant role in glioblastoma survival as well as in its tumour growth. It was seen that endocan does not only help in tumour growth but also plays a role in mapping of tumour where that geographical margin consists of aggressive edges.

After they are surgically removed, these regions form the edges which make the tumor grow back. Endocan is implicated in the construction of new blood vessels through which the tumor is supplied with the required nutrients, which means that it is very difficult to destroy this type of tumor.

Endocan-PDGFRA Interaction and Treatment Resistance

Endocan has shown antecedents with the PDGFRA receptor and it has been associated with the resistance of glioblastoma to regular treatments such as radiation. Endocan has been found to be overexpressed in tumors that have higher radioresistance, a vital and standard treatment for glioblastoma. Therefore, this research underlines the importance of using the endocan-PDGFRA axis in designing new treatment strategies.

Here, the researchers show that this action using ponatinib, the targeted therapy drug can increase the survival rate in preclinical models and also improve the sensitivity of the tumor to radiation therapy. This approach presents a novel strategy to identify new therapies that can both inhibit tumor progression and enhance the effectiveness of current medicine.

The link with cMyc and potential therapeutic directions

It also identified that endocan's activity is associated with cMyc, a protein implicated in many types of cancer but which is hard to target therapeutically. Interference with the endocan-PDGFRA signaling could provide an indirect way to inhibit cMyc thus contributing to improving the treatment of glioblastoma.

This study also describes endocan's function in glioblastoma related to growth, survival and treatment resistant inspiration. Through the restitution of the molecular process associated with endocan and PDGFRA, new therapeutic approaches have been proposed in order to build on existing treatments that not only slow the growth of the cancer but also increase the sensitivity of glioblastoma to the standard treatments such as radiation. The results of the study provide hope toward enhancing the survival of this often deadly form of brain cancer.

Reference:

Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma - (https:www.nature.com/articles/s41467-024-55487-1)

Source: Medindia

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