A team of researchers from the Tokyo University of Science and other institutes have developed a first-of-its-kind cancer treatment strategy that targets a pro-tumor protein ‘FROUNT’ and suppresses Tumor-Associated Macrophages (TAMs).
The TAMs are the host macrophages recruited by the tumor, which advance tumor progression. The protein FROUNT may be associated with TAM regulation.
It may be possible to disrupt this tumor progression, by inhibiting FROUNT using an anti-alcoholism drug - disulfiram.
One of the toughest challenges in medical research is to develop a therapy to fight cancer and this deadly disease owes its notorious identity to the fact that cancer cells utilise the host's immune system to grow and spread, finally turning out to be deadly.
The immune cells like macrophages, which fight to protect normal cells, are attacked by malignant cancer cells, and populate the environment around the tumors, becoming TAMs.
It was found that the cancerous tissues of patients for whom immunotherapy was unsuccessful were indeed rich in macrophages, thus confirming the connection between cancer and the TAMs.
These TAMs are responsible for producing signaling proteins like chemokines and produce the inhibitory immune checkpoint releases that create an immunosuppressive tumor environment, which protects the cancer cells and allows their accelerated growth.
In their research, it showed that the target protein is linked to the regulation and movement of the TAMs. Since FROUNT improvised ‘chemokine signaling’ (a type of cellular communication, an integral process for TAM accumulation and activity), it was therefore linked directly to TAM regulation.
With animal experiments, the team found out that by regulating the FROUNT expression in TAMs, the cancer growth could be suppressed.
An independent strategy of limiting the effect of FROUNT on chemokine signaling was also developed by the team to reduce any side effects, by inhibiting the interaction between the two.
Around 1,31,200 compounds were screened and zeroed in on disulfiram. The drug was found to directly bind to the FROUNT site, making FROUNT unavailable for interaction with the components of chemokine signaling.
When experimented on mice, disulfiram inhibited the movement of macrophages and suppressed the growth of cancer cells. Therefore, it was found that a new cancer treatment strategy can suppress the cancer cell growth that is difficult to respond by immune checkpoints when used in combination with disulfiram.