Battling Brain Cancer: The Urgent Quest to Find Answers
As researchers sift through the clues about how glioblastoma grows, one area of focus is on the unique way cancer cells replicate in the brain.
A Devastating Diagnosis
To be diagnosed with brain cancer is to be confronted with a new sense of urgency.
Immediately after diagnosis, people with glioblastoma face a combination of approaches – surgery, radiation and chemotherapy – to treat the disease aggressively.1 Even with swiftly executed plans of attack, the disease recurs in about 90 percent of patients.2
This devastating form of cancer, with a median life expectancy of 15 months from the time of diagnosis , inspired former president Barack Obama and former vice president Joe Biden to launch the Cancer Moonshot initiative following the death of Biden’s son, Beau, in 2015.
“Part of the moonshot is my view from my perspective … of Beau, and the life he lived of courage, and never giving up hope. This isn’t about him, this isn’t about a single person, it’s about us not giving up hope and having the urgency of now,” Biden says.
That urgency is palpable for those living with glioblastoma, their loved ones and physicians treating the disease. Glioblastoma is the most common type of malignant brain tumor, and an estimated 12,000 new cases are predicted in 2017.4
As researchers sift through the clues glioblastoma offers about how it grows and eludes different types of treatments, one area of focus is on the unique way cancer cells replicate in the brain.
Copy, Paste, Repeat
For about 40 to 50 percent of patients5 with glioblastoma, it starts with the EGFR.
Simply put, EGFR is a protein that plays a critical role in the growth and regeneration of different cell types throughout the epidermal layers of the body, like the skin or the lining of the lungs.
“Our skin cells and any cell that comes from the epidermis have a normal amount of EGFR. It’s part of the normal processes for cell growth,” says Kyle Holen, M.D., executive medical director, oncology development, AbbVie.
But certain types of cancerous cells seize the epidermal growth factor receptor (EGFR) to grow uncontrollably and spread to other organs.
“Cancer cells use this receptor to make the cancer grow a little bit faster and spread and invade into different organs. And each cancer uses the cancer growth factor receptor in a different way,” Holen says.
What is unique in about 40 to 50 percent of glioblastomas is that there are an abnormally high number of copies of EGFR DNA, called EGFR amplification.7
"Amplification refers to the fact that the gene that encodes EGFR has multiple copies. Subsequently, this leads to large amounts of protein – hundreds of thousands of EGFR molecules expressed on the surface of that cell. And what we know is that EGFR gene amplification is primarily restricted to glioblastoma,” says Ed Reilly, Ph.D., senior research fellow, project director, oncology discovery, AbbVie.
Because EGFR amplification and overexpression are striking features of glioblastoma,8 scientists are exploring how to turn EGFR against the tumor itself.
“In clinical trials, we’re investigating how to use EGFR as the address to deliver a potent toxin to the cancer cell. In essence, we’re trying to exploit the major tumor driver in this disease in order to deliver the treatment,” Holen says.
The investigational treatment is currently in Phase 2 clinical trials.
The Challenges Ahead
While researchers uncover more about EGFR and how it could be used to treat glioblastoma, they continue to face a crafty foe that finds new ways to survive.
“It’s hard not to focus on individual patients and see how this horrendous disease highlights more than anything the urgent need to develop new therapies for glioblastoma.”
“There are a huge mix of dis-regulated genes, which means that glioblastoma can adapt to attack and develop resistance (to treatments) pretty quickly and find other ways to grow,” Holen says.
But the urgency and motivation to press on for those impacted by glioblastoma remains.
“It’s hard not to focus on individual patients, at least from my perspective, and see how this horrendous disease highlights more than anything the urgent need to develop new therapies for glioblastoma. All of us are motivated by the ability to hopefully have a positive effect on patients where few other options are available,” Reilly says.
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1 National Brain Tumor Society web site. "Tumor Types: Understanding Brain Tumors." http://braintumor.org/brain-tumor-information/understand-ing-brain-tumors/tumor-types/ #glioblastoma-multiforme. Accessed March 2017.
2 Roy, S, Lahiri, D., Maji, T, and Biswas, J. Recurrent Glioblastoma: Where we stand. South Asia J Cancer (2015) 4(4): 163 - 173.
3 National Brain Tumor Society web site. "Tumor Types: Understanding Brain Tumors." http://braintumor.org/brain-tumor-information/understand-ing-brain-tumors/tumor-types/ #glioblastoma-multiforme. Accessed March 2017.
4 American Brain Tumor Association. “Brain Tumor Statistics.” http://www.abta.org/about-us/news/brain-tumor-statistics/. Accessed May 8, 2017.
5 Yoshimoto, K, Dang, J., Zhu, S., et al. Clin Cancer Res 2008; 14:488-493.
6 HGNC:HGNC:3229. “EGF Epidermal Growth Factor.” https://www.ncbi.nlm.nih.gov/gene/1950. Accessed May 4, 2017.
7 Yoshimoto, K, Dang, J., Zhu, S., et al. Clin Cancer Res 2008; 14:488-493.
8 Hatanpaa, Kimmo J., et al. Neoplasia. “Epidermal Growth Factor Receptor in Glioma: Signal Transduction, Neuropathology, Imaging, and Radioresistance.” V.12(9); Sept. 2010. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933688/. Last accessed May 4, 2017.