【Cancer Cell】New! The Weill Cornell team identified potential treatments for metastatic colon cancer

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Written by Sophia

Mesenchymal colorectal cancer (mCRC) is microsatellite-stable (MSS), highly connective tissue hyperplasia, CD8 T cells are excluded from the peristromal periphery, resistant to immunotherapy, and driven
by low levels of atypical protein kinase Cs (aPKC) in the intestinal epithelium.

According to a new study by Weill Cornell Medical researchers, an experimental therapy has shown promise
in preclinical models as a treatment for colorectal cancer.
The study was published Dec.
15 in
the journal Cancer Cell.

style="box-sizing: border-box;" _msthash="251139" _msttexthash="381004">Research background

 01 

Mesenchymal colorectal cancer accounts for about one-third
of all colorectal cancers.
Targeted immunotherapy is ineffective against this cancer because the environment inside the tumor blocks the immune cells that kill the tumor cells
.
But a team led by Dr.
Maria Diaz-Meco and Dr.
Jorge Moscat has shown that the accumulation of a molecule called hyaluronic acid is a key step
in the formation of mCRC tumors.
The study also demonstrated that experimental therapies targeting hyaluronic acid could shrink mCRC-like tumors
in mice.

A previous study by the team showed that patients with reduced levels of two enzymes called PKCz and PKCi were more likely to develop mCRC tumors and had a worse
prognosis.
When the genes encoding these enzymes were turned off in mice, the animals developed mCRC-like tumors
.
"These two enzymes are gatekeepers," Dr.
Moscat said
.
"When they're lost, it immediately initiates tumor formation
.
"

Research progress

 02 

Research has revealed one of the key mechanisms driving this aggressive colorectal cancer, and we are proposing a potential treatment
for patients who currently have few options.

Using animal models and single-cell analysis of tumors, the study showed that hyaluronidase sensitizes tumors to
immunotherapy.
The first step in the process is the accumulation of hyaluronic acid, which begins before the tumor forms
.
Hyaluronic acid attracts connective tissue cells
called fibroblasts.
These cells encourage the development of the most aggressive tumor cells and shut down the immune system's ability to
kill tumor cells.

But in mice, mCRC-like tumors were treated with an experimental therapy called hyaluronidase, which breaks down hyaluronic acid, shrinks tumors and allows immune cells to attack tumor cells
.
Combining targeted immunotherapy anti-PD-L1 and anti-CTLA-4 antibodies with hyaluronidase virtually eliminated mCRC tumors
that had spread to the animal's liver.
Dr.
Diaz-Meco explains that this is particularly exciting because liver metastases are common in patients with metastatic colorectal cancer and are difficult to treat
.

The team also identified biomarkers that may help determine which patients with metastatic colorectal cancer will benefit from hyaluronidase treatment
.
They are currently conducting clinical trials in collaboration with clinical
partners.
Clinical trials of hyaluronidase as a treatment for pancreatic cancer have shown that the drug is safe and has controlled side effects, but this therapy is not effective
for pancreatic cancer.

Research significance

 03 

The team is also looking for ways to
prevent metastatic colorectal cancer from developing or spreading.
They want to understand how guardian enzymes are lost before cancer flares up, and whether they can find treatments that block hyaluronic acid production to prevent cancer from metastasizing or spreading
.
This treatment may be particularly beneficial for people at high risk of colorectal cancer, such as those with ulcerative colitis or inflammatory bowel disease
.
If this process can be stopped by removing hyaluronic acid, it prevents tumors from forming or spreading to the liver, making it easier to treat
.

Resources:

https://medicalxpress.
com/news/2022-12-preclinical-team-potential-therapy-metastatic.
html

style="white-space: normal;box-sizing: border-box;">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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