【Nature】New study discovers for the first time residual tumor cells that cause colorectal cancer metastasis to recur!

This article is the original of Translational Medicine Network, please indicate the source for reprinting

Author: Mia

About 30-40% of colorectal cancer (CRC) patients who undergo radical resection of the primary tumor will develop metastases
in subsequent years.
Preventing disease recurrence remains an urgent medical need
.
Recently, a research team discovered for the first time the identity and characteristics
of residual tumor cells that cause CRC recurrence.

On November 9, 2022, researchers from the Institute of Science and Technology in Barcelona, Spain, published a research paper
titled "Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells" in Nature.
The study is the first to identify residual tumor cells hidden in the liver and lungs and reveals how these residual cells evolve into metastases
that appear in the liver and lung organs.

https://doi.
org/10.
1038/s41586-022-05402-9

Research background

 01 

Colorectal cancer (CRC) is a common malignant tumor, and the incidence and mortality are increasing year by year
.
According to the American Cancer Society's 2021 statistics, CRC incidence and mortality in the United States rank 3rd
among both men and women.
According to the latest statistics of the National Cancer Center, the number of new CRC cases in China accounts for 9.
9%
of all new malignant tumors.

About 20% of colorectal cancer patients are at an advanced stage of disease at the time of diagnosis, while 30-40% of colorectal cancer (CRC) patients who undergo radical resection of primary tumors will have metastases, and metastasis of important organs and recurrence after surgery remain the main causes
of death.
However, there is still a lack of effective therapies to eliminate residual tumor cells to prevent colon cancer metastasis and recurrence
in poorly prognostic colon cancer.

Highly recurrent cells were first identified

 02 

In this study, the researchers performed single-cell transcriptome analysis
on samples from CRC patients.
They found that most of the genes associated with poor prognosis were expressed by a unique population of tumor cells, which the researchers named high relapse cells (HRCs
).

The research team established a microsatellite-stabilized humanoid mouse model of CRC to simulate the process
of metastatic recurrence after surgical removal of the primary tumor.
After primary CRC surgery, residual HRCs in the livers of mice had little proliferative activity and did not contribute
to the growth of primary colon cancer.
But over time, residual HRCs produce a variety of cell types, including LGR5 stem cell-like tumor cells
.
This group of HRC cells is able to break away from primary colon cancer, migrate into the bloodstream, reach the liver, and hide for a while after surgery, subsequently triggering significant metastatic disease
.

Subsequently, the researchers tracked and selectively eliminated this cell population
using EMP1 (encoding epithelial membrane protein 1) as a marker gene for HRCs.
Genetic ablation of EMP1^high cells prevented metastatic recurrence and maintained the disease-free state
of the mice after surgery.
In addition, HRC-rich micrometastases were found to be infiltrated by T cells, but gradually immune rejection
during growth.
In summary, this neoadjuvant immunotherapy eliminated residual metastatic cells and prevented postoperative recurrence in mice
.

Research significance

 03 

In summary, the new findings reveal the dynamics of cellular state of CRC residual lesions and predict that treatments targeting HRCs may help avoid metastatic recurrence
.
The researchers say the work also represents a proof of concept that could pave the way for the development of new therapies, particularly aimed at eliminating residual disease and developing new diagnostic tools to identify those patients
most at risk of relapse.
Finally, because immunotherapy before surgery will be more effective, it is necessary to revise clinical guidelines
for the treatment of this type of cancer.

Resources:

https://doi.
org/10.
1038/s41586-022-05402-9

Note: This article is intended to introduce the progress of medical research and cannot be used as a reference
for treatment options.
If you need health guidance, please go to a regular hospital
.

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