Breast Cancer: Immunotherapy uses the immune system to fight breast cancer, helping our body’s natural defence to recognize and attack cancerous cells. It is the usual course of treatment for certain cancers and can be used either alone or in conjunction with other therapies including radiation, chemotherapy, or surgery. However, a news release from Stanford University regarding the scientific discovery stated that immunotherapies are ineffective in treating many tumors, including more than 80% of some of the most advanced breast cancers. It also stated that a large number of people whose cancer does respond to immunotherapy subsequently develop metastases. When cancer spreads to other body parts, it is called metastasis.
Breast Cancer Breakthrough
A particular protein known as ENPP1 has been found to function as an on/off switch. It determines whether breast cancer may withstand immunotherapy and metastasis. The team lead by Lingyin Li, an associate professor of biochemistry at Stanford and Arc Core Investigator, identified this protein.
According to researchers, immunotherapies function by preventing a cancer cell. It also includes a T cell, a kind of immune cell, from interacting in a way that compromises the immune system.
However, T cells must enter the tumour for this to work.
“Hot” tumors are those that respond well to immunotherapy; “cold” tumors are those that are immune system-impermeable and cannot be invaded by T cells.
Dr. Li started heating up cold tumours.
She saw how malignant cells release a chemical known as cGAMP. It triggers the STING pathway, an immunological response that can help a tumor become heated and react to immunotherapy.
The researcher had previously found that a protein known as ENPP1. It can inhibit this immune response, preventing a cancer from reacting to the therapy.
Researchers found that “poor prognosis in many cancers correlates with high levels of ENPP1.”
Examining data from a novel breast cancer trial, they sought to determine if patient response to therapy was influenced by ENPP1 levels.
The researchers wrote, “The results were astounding.”
High ENPP1 levels were associated with poor response to pembrolizumab, the treatment being administered, and a higher risk of metastases.
In contrast, patients with low ENPP1 levels did not develop metastases and responded well to pembrolizumab.
Then, in order to learn more about this phenomena, the researchers ran a number of mice experiments.
Using molecular scalpels, the researchers discovered that blocking ENPP1 reduced cancer growth. Metastasis in mice, according to a report published in the Proceedings of the National Academy of Sciences.
This suggests that medications that break the ENPP1 dam may improve the efficacy of current therapies and that clinicians may utilise ENPP1 levels to better decide the optimal course of treatment for patients with breast cancer.
The researchers pointed out that several ENPP1 inhibitors are currently undergoing clinical development. “Our study should offer hope for everyone,” Dr Li said.
While this work focused on breast cancer, Li believed that ENPP1 plays a critical role in other kinds of “cold” tumours.
“I hope to inspire clinicians who treat cancers – including lung cancer, glioblastoma, and pancreatic cancer – to investigate ENPP1’s role in patient outcomes,” she said.