Can these anti-cancer targets also take into account weight loss? The more weight you lose, the lower your risk of cancer!

With the continuous improvement of human living standards, the prevalence of obesity is increasing worldwide, and the impact of obesity-related cancers on public health is increasing
.
At the same time, the increase of lipids can promote the ability of tumor cells to develop, colonize and metastasize, and cancer cells also use lipid metabolism to regulate the activity of stromal cells and immune cells, thereby resisting treatment and promoting cancer recurrence
.

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

Author: kope

Many previous scientific studies have shown that obesity is associated with
the development of a range of diseases.
For example, heart disease, diabetes and even the occurrence of certain cancers are all associated
with obesity.
So the question is, does this mean that through deliberate weight loss, the incidence of these related diseases will also decrease?

Obesity-related cancer incidence

 01 

Globally, 1.
9 billion adults are overweight and 600 million are obese, and 51% of the world's population is expected to be obese by 2030
.
Obesity not only affects appearance and daily life, but also causes metabolic syndrome, which brings various health problems, such as type 2 diabetes, high blood pressure, non-alcoholic steatohepatitis, cardiovascular disease and cancer
.
Obesity is closely related to the body's metabolism and immune function, and one of the key features is that obesity causes chronic inflammation and promotes metabolic syndrome
.
However, the specific mechanisms behind this phenomenon have not been studied in depth
.

Not long ago, the team at Cleveland Clinic published an article entitled "The Association between Bariatric Surgery and Cancer Risk and Mortality in Obese Adults" in the Journal of the American Medical Association (JAMA), exploring the relationship
between bariatric surgery and cancer risk and mortality in obese patients.

On November 5, 2022, the Journal of Clinician Cancer (CA) also published an article entitled "Sustained weight loss can reduce cancer risk", recognizing the research results and publishing relevant comments
.
The original study, published in JAMA, showed that obesity-related cancer rates were reduced by 32% and cancer-related mortality by 48%
after obesity adults who achieved weight loss through bariatric surgery.

Metformin with GDF15

 02 

GDF15 is also thought to be a negative regulator of anti-tumor T cell activity, associated with suppressing the immune response and preventing T cells from being recruited into the tumor microenvironment
.
Studies have shown that GDF15 plays an important role
in the pathogenesis of various diseases such as tumors, ischemic diseases, metabolic disorders, and neurodegenerative diseases.

Growth differentiation factor 15 is an endocrine hormone discovered in 1997, GFRAL is expressed only in the hindbrain, this receptor activation can lead to reduced food intake and weight loss, hence the GDF15 is called "anorexia hormone"
。 A large number of studies have shown that the increase in GDF15 level is related to cardiovascular diseases such as myocardial hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, as well as obesity, diabetes, cancer, cachexia, etc.
, which have been confirmed to be new biomarkers for the diagnosis, progression or prognosis of the above diseases, and the discovery of GDF15 has laid the foundation for target-based new drug development
。

As the star molecule of anti-diabetic drugs, the anti-obesity effects of metformin have also been shown to be associated with GDF15, which can increase serum GDF15 levels, reduce food intake and reduce body weight by limiting the brainstem, and is not associated with
lowering blood sugar.
GDF15 has been shown to be a biomarker for abnormal blood sugar in patients taking metformin, and its concentration reflects the dose
of metformin.
In addition, elevated serum GDF15 in people with type 2 diabetes taking metformin was also associated with
weight loss.
Based on this, it is possible
to develop drugs based on the GDF15-GFRAL-RET receptor signaling complex in the brain to treat cachexia caused by obesity and cancer.

Anti-cancer star PD-L1

 03 

In recent years, immunotherapy represented by PD-1/PD-L1 immune checkpoint inhibitors has greatly changed the treatment pattern of a variety of cancers and benefited many cancer patients
.
However, PD-L1's role may not be limited to this
.

A recent study by an Irish research team showed that PD-L1 on dendritic cells (DCs) can control adaptive immune responses within adipose tissue, thereby suppressing diet-induced obesity
.
In mice on a high-fat diet, PD-L1 deficiency in dendritic cells promotes increased obesity and impaired
polarization of adipose tissue T cells.

PD-L1 also plays such a regulatory role in human adipose tissue, and the expression of PD-L1 in visceral adipose tissue is positively correlated
with weight gain in obese individuals.
Thus, the study defines a adipose tissue homeostasis mechanism controlled by dendritic cell expression of PD-L1, which may be associated with
immune-related adverse events during immune checkpoint inhibitor therapy.
This discovery provides a new way to regulate adipose tissue inflammation and also provides new ideas
for the treatment of obesity.

Resources:

Acta Pharmaceutica Sinica, 2021, 56(10): 2728-2734.

https://jamanetwork.
com/journals/jama/fullarticle/2793220

style="white-space: normal;margin: 0px;padding: 0px;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
.