Metastasis, the leading cause of cancer-related death, arises primarily from the “seed” of secondary organs by disseminated tumor cells (DTCs, DTCs) that persist in the body before triggering symptomatic overt metastases Dormant for years or decades. Recently, in a research report titled “An NR2F1-specific agonist suppresses metastasis by inducing cancer cell dormancy” published in the international journal Journal of Experimental Medicine, scientists from Mount Sinai Icahn School of Medicine and other institutions found that a A new therapeutic approach may prevent the growth of metastatic tumors by promoting cancer cells to enter a dormant state in which they cannot proliferate. Related research results may help to develop new treatments that are effective in preventing the recurrence and metastatic spread of many types of cancer, including breast cancer and head and neck squamous cell carcinoma (HNSCC).
Many cancer patients experience relapse, which often results in new tumors forming in the same location in the body or metastasizing to other parts of the body years or decades after initial treatment; these secondary tumors often respond to therapy. Tolerance, produced by a single tumor cell, tends to lie dormant for long periods of time before being reactivated to proliferate, so if researchers can find a way to put remaining cancer cells in a dormant state , can effectively prevent disease recurrence in patients.
In previous studies, the researchers found that the ability of cancer cells to remain dormant may be controlled by a protein called NR2F1, a receptor protein that travels to the nucleus and turns the expression of various genes on or off, thereby activating A program that prevents the proliferation of cancer cells. NR2F1 levels are usually low in primary tumors but high in dormant, spreading cancer cells; when cancer cells start multiplying again and form recurrent or metastatic tumors, NR2F1 protein levels drop again .
”We therefore believe that activating NR2F1 with a small molecule may be a very attractive clinical strategy to induce dormancy in cancer cells and prevent cancer recurrence and metastasis, among other things,” explains researcher Aguirre-Ghiso. In the article, the researchers used a computer-based screening strategy to identify a drug called C26 that activates NR2F1 expression, and found that treating patient-derived HNSCC cells with C26 may enhance NR2F1 levels and prevent cell proliferation.
The researchers then tested whether C26 could prevent the cancer from metastasizing in mice. Animals injected with HNSCC cells derived from patients often developed larger primary tumors that remained intact after surgery to remove the primary tumors. spread to the lung tissue; treatment with C26 can reduce the size of the primary tumor, and when surgery is given, a further dose of C26 can completely block the growth of metastatic tumors; in contrast, rodent lung The tumor contains only a small number of dormant and spreading cancer cells, which cannot proliferate even after stopping treatment. Now researchers have determined that by activating NR2F1, C26 promotes a long-term dormancy in cancer cells that manifests as a unique pattern of gene activity; cancer patients whose tumors exhibit similar patterns of gene activity may tend to live longer And the disease did not relapse, suggesting that using C26-type drugs to induce this cell dormancy program may be very effective in humans.
Researchers Sosa pointed out that drugs that activate NR2F1 may be particularly effective in the treatment of breast cancer. Compared with ER-negative tumors, NR2F1 is highly enriched in ER-positive tumors, and activating NR2F1 may inhibit the maintenance of breast cancer due to anti-estrogen therapy. Dormant cancer cells in this state revive; however, since C26 therapy increases NR2F1 levels, this approach may also be useful for other cancers with lower levels of the receptor protein. Taken together, our findings suggest that we have uncovered a novel mechanism-based and rationally designed strategy that may exploit NR2F1-activated dormancy as a therapeutic option to prevent metastatic recurrence of cancer.
