5th November 2021
New way to infiltrate hard-to-treat cancers
Researchers at George Washington University in Washington, DC, have identified a key molecule in certain kinds of breast cancers that prevent immune cells from entering tumours and killing the cancer cells inside. This finding could pave the way toward new treatments for some aggressive forms of breast cancer.
"During cancer progression, this molecule – known as DDR1 – organises a high-order extracellular matrix that acts like barbed wire around the boundary of a tumour to prevent immune cells from entering the tumour," said Rong Li, Chair and Professor of the Department of Biochemistry and Molecular Medicine at the George Washington University (GWU). Dr. Li is the lead author of a paper published this week in the journal Nature.
"Knowing that the DDR1 molecule creates a protective boundary around tumours, we were able to use pre-clinical models to show that the moment you deactivate DDR1, immune cells can infiltrate the tumour and kill the cells inside," he said.
Dr. Li and his colleagues studied triple-negative breast cancer, an aggressive form of the disease that accounts for about 15% of all breast cancer cases. This type of cancer, according to the Centers for Disease Control and Prevention, lacks the receptors commonly used in targeted cancer therapies, making it difficult to target the tumour cells. Immunotherapy is designed to activate immune cells when they can get to the centre of a tumour, but the DDR1 molecule puts up a physical barrier to anti-tumour immune cells. Identifying the underlying mechanism could provide a new way of looking for novel therapeutic agents for this hard-to-treat cancer, Dr. Li said.
Immune cells (red), collagen fibres (grey), and the tumour margin (denser grey-white area in the bottom left). Credit: GW Nanofabrication and Imaging Center
In their study, the researchers at GWU assessed the impact of removing DDR1 in multiple pre-clinical models. They determined that knocking out DDR1 not only halts tumour growth, but may also protect the body from future tumours.
In conjunction with the new findings, co-corresponding author Zhiqiang An has developed a therapeutic DDR1-targeting antibody that breaks down that line of defence and helps tumour-killing immune cells cross.
"The discovery of the important role of DDR1 in cancer resistance is a significant advance that can potentially transform treatment pathways," said Dr. An, who is director of the Texas Therapeutics Institute and Professor of Molecular Medicine at the University of Texas Health Science Center, Houston. "I'm delighted by the collaboration between researchers and academic labs, excited by synergies of basic and translational research, and encouraged by the rapid translation from discovery to therapeutic candidates for the benefit of people living with cancer."
With this more comprehensive understanding of DDR1, the researchers also hope to identify additional molecules like DDR1 and use the same approach to fight other cancer types.