SCIENTISTS have pinpointed a critical ‘off switch’ that controls breast cancer’s ability to resist treatment and spread.
Immunotherapy uses the immune system to fight cancer, helping our body’s natural defence to recognise and attack cancerous cells.
Lingyin Li and Songnan WangSongnan Wang (left) and Lingyin Li (right) found that a protein called ENPP1 acts as an on/off switch for breast cancer metastases[/caption]
It can be had on its own or in combination with other therapies – such as surgery, chemotherapy or radiotherapy – and is used as the standard course of treatment for some cancers.
But immunotherapies fail to treat many cancers, including over 80 per cent of some of the most advanced breast cancers, a Stanford University press release about the scientific breakthrough claimed.
Many of the patients whose cancer does respond to immunotherapy still experience metastases eventually, it added.
Metastasis occurs when the cancer spreads to other parts of the body.
A team led by Lingyin Li, associate professor of biochemistry at Stanford and Arc Core Investigator, identified a specific protein called ENPP1 that acts as an on/off switch to control whether breast cancer can resist immunotherapy and metastasise.
Immunotherapies work by blocking an immune-dampening interaction between a cancer cell and a T cell, which is a kind of immune cell, researchers said.
But for this to be effective, T cells need to get into the tumour.
Tumours that are treatable by immunotherapy are called “hot”, but those that aren’t are called “cold” and can’t be permeated by T Cells.
Dr Li set about turning cold tumours hot.
She observed how cancerous cells produce a molecule called cGAMP, which activates an immune response called a STING pathway, that can help a tumour become hot and respond to immunotherapy.
The scientist had previously discovered how a protein called ENPP1 can stop this immune response, stopping a tumour from responding to the treatment.
“High levels of ENPP1 correlate with poor prognosis in many cancers,” researchers wrote.
They looked at data from a groundbreaking breast cancer trial to identify whether ENPP1 levels had anything to do with how patients responded to treatment.
“The results were astounding,” researchers wrote.
Patients with high ENPP1 levels had low response to pembrolizumab, the immunotherapy being used, and high chance of metastases.
Meanwhile, those with low ENPP1 levels had a high response to pembrolizumab and no metastases.
The researchers then conducted a series of mouse studies to further study this phenomenon.
Using molecular scalpels, they found that removing ENPP1 decreased tumour growth in mice and decreased metastases too.
This proved that these better outcomes resulted directly from suppressing the STING pathway, the study published the Proceedings of the National Academy of Sciences, stated.
This means that clinicians can use ENPP1 levels to better determine appropriate treatment for breast cancer patients and that drugs that destroy the ENPP1 dam could make existing therapies more effective.
Several ENPP1 inhibitors are already in clinical development, the researchers noted.
“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.