Amongst the more common targets for cancer therapies are cell surface receptors. These receptors are proteins – usually involved in transmitting signals into the cell – and are key signal gateways. Therefore, blocking a single receptor could stop whole signal pathways in the cell and maybe even stop cancer in its tracks.
Researchers have identified a new receptor, formylpeptide receptor 1 (FPR1), that might be a good target for anti-cancer drugs. This receptor is part of a family of receptors involved in chemotaxis (a part of how cells move) for immune cells called leukocytes. Recent studies have found that FPR1, in particular, plays a pro-cancer role in many tumor types.
In a new study, a team out of the University of Bradford in the United Kingdom wanted to investigate if FPR1 played a role in colorectal cancer. Other studies have already linked it to brain, colon, and breast cancers, but there wasn’t any evidence of it playing a part in colorectal cancer. There is even evidence that it has a role in resistance and recurrence.
The team would analyze FPR1 expression in colorectal cancer in vitro and in vivo with several other cancer types used as controls to investigate their hypothesis. They would also test how a robust FPR1 inhibitor, developed by the same team in a previous study, would affect cancer cells in the same models.
They first investigated FPR1 levels in a variety of cancer cell lines in vitro. They found that colorectal cancer indeed had FPR1 levels similar to other studied cancers. They also saw an interesting correlation between FPR1 levels and ANXA (an activator of FPR1) levels in hypoxic/necrotic conditions in the brain cancer cell line both in vitro and in vivo.
After the interesting finding with the brain cancer cell line, the team decided to pivot to investigating FPR1’s role there. They tested the FPR1 inhibitor they had developed in a previous study, ICT12035 could prevent the FPR1 dependent cancer growth. They induced FPR1 using an activator molecule, fMLF, which increased cell invasion in the brain cancer cell line. The inhibitor's application effectively prevented this increase in cell invasion and could even suppress cancer cell growth in mouse models.
This study showed that FPR1 was indeed expressed in colorectal cancer as in other cancer types. After an interesting find in a brain cancer cell line, the team shifted their testing. Using the brain cancer cell line, they saw that the FPR1 inhibitor ICT12035 could suppress cancer growth both in vitro and in a mouse model. They also saw that hypoxic conditions, often found in tumors, have higher levels of FPR1, inferring the receptor may play a role in tumor formation or maintenance.
The study concludes, “Further investigation of ICT12035, or other FPR1 antagonists, can open opportunities for more efficient treatment for cancers, including glioma, in due course.”
Sources: Nature Scientific Reports, khanacademymedicine