Nat Commun: Genomic research may reveal potential combination therapy or effective treatment of triple-negative breast cancer

News from June 9, 2021 // - Breast cancer is the leading cause of cancer deaths in women worldwide.
Every day, about 1,700 people die from the disease worldwide; although most breast cancers are treatable, the most The aggressive subtype of breast cancer-triple-negative breast cancer (TNBC) has a high recurrence rate, high metastasis potential, and often has a certain tolerance to conventional therapies, resulting in poor prognosis and poor quality of life for patients
.

Recently, a research report entitled "In vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR/Hippo targeted combination therapy" was published in the international journal Nature Communications .

Nature Communications scientists from McGill University Health Center and other institutions have conducted a preclinical study and found that a new type of targeted combination therapy may effectively reduce tumor growth in patients with metastatic breast cancer.

Image source: https:// Jean-Jacques Lebrun said that there are currently no targeted therapies for triple-negative breast cancer.
Chemotherapy will even make these tumors rich in cancer stem cells and will have adverse effects on patients, as we have observed in previous studies.
As it is
.

Although most breast cancers have one of the three common main receptors, it is like the gateway to therapy, namely estrogen receptor, progesterone receptor, and a receptor called human epidermal growth factor receptor ( HER2) protein, but triple-negative breast cancer does not have the above three receptors.

First of all, in the first part of the study, the researchers identified 150 new genes, which can either induce tumor formation (carcinogenic) or inhibit tumor formation (tumor suppressor).
In order to achieve this goal, the researchers identified a triple negative Nearly 20,000 genes (the entire human genome) were screened in a preclinical mouse model of breast cancer.
Using CRISPR/Cas9 gene editing technology, they cut out each gene and induced its loss of function (ie gene knockout).
So far, few studies have used these in vivo CRISPR screening technologies on a genome-wide scale
.

Later, the researchers found that in triple-negative breast cancer, the oncogenic pathway mTOR is activated, while another tumor suppressor pathway called Hippo is inhibited, which may help explain why these tumors are so aggressive and lethal.
Sex
.

In order to determine the therapeutic relevance of the results of this article, the researchers conducted further in-depth research

In triple-negative breast cancer, the oncogenic pathway mTOR is activated, while another tumor suppressor pathway called Hippo is inhibited, which may help explain why these tumors are so aggressive and lethal

Perform in vivo genome-wide CRISPR knockout screening in triple-negative breast cancer
.

Image source: Dai, M.
, et al.
Nat Commun 12, 3055 (2021).
doi: 10.
1038/s41467-021-23316-4

Nat Commun

The researchers’ findings exceeded their expectations.
The two drugs can work in a synergistic manner.
After studying a xenograft model derived from cells and the patient’s body, they found that these two drugs may be effective in reducing tumors.
Growth in vivo and in vitro
.

In the experiment, the researchers noticed that verteporfin may induce cell death through apoptosis, while Torin1 is induced through a non-apoptotic mechanism-macropinocytosis.

Torin1 induces cell death through a non-apoptotic mechanism-macropinocytosis.

The research results in this article have identified a new method that can effectively inhibit tumor formation and reduce the burden of tumors, that is, the size of the tumor, the level of cancer in the body, etc.
, by targeting both cancer-promoting and tumor-suppressing mechanisms or signaling pathways.
The targeted combination therapy proposed for triple-negative breast cancer patients may help fill an important medical gap in the field of metastatic breast cancer research
.

In summary, this study emphasizes the power and robustness of using in vivo CRISPR genome screening in cancer research to identify clinically relevant and innovative cancer therapeutic models

This study emphasizes the power and robustness of using in vivo CRISPR genome screening in cancer research to identify clinically relevant and innovative cancer therapeutic models

Original source:

Original source:

Dai, M.

Dai, M.
, Yan, G.
, Wang, N.
et al.
In vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR/Hippo targeted combination therapy .
Nat Commun 12, 3055 (2021).
doi: 10.
1038/ s41467-021-23316-4 In vivo genome-wide CRISPR screen reveals breast cancer vulnerabilities and synergistic mTOR/Hippo targeted combination therapy Nat Commun