Understanding the Causes of Weight Loss in Cancer Patients and Strategies for Prevention
A recent study suggests the possibility of early diagnosis and treatment of wasting syndrome, a life-threatening side effect of cancer. While the immune system’s response of triggering inflammation-causing white blood cells is beneficial for healing wounds, the same response within cancerous tumors leads to tumor growth and a severe condition known as wasting syndrome. This syndrome is characterized by rapid weight loss unrelated to the patient’s diet and affects a significant percentage of cancer patients, contributing to approximately 20% of cancer-related deaths. Israeli researchers, in an article published in Cancer Discovery, shed light on the underlying mechanism of this syndrome and propose a predictive method, offering potential avenues for treatment. Despite the crucial importance of maintaining the patient’s overall well-being to combat cancer, there is currently no established treatment for wasting syndrome, as highlighted by lead researcher Omer Goldman from Prof. Ayelet Erez’s molecular cell biology research team at the Weizmann Institute of Science.
In the study conducted by Goldman, metabolic changes were monitored in mouse models representing human breast and pancreatic cancers. The focus was on the urea cycle, which involves a series of biochemical reactions occurring in the liver. This cycle converts excess nitrogen, in the form of ammonia, into urea for elimination through urine.
Goldman observed a decline in urea cycle activity shortly after the cancer onset. Consequently, there was an accumulation of amino acids in the bloodstream of the mice, rather than their breakdown within the cycle. The tumor utilized these amino acids to construct its RNA and DNA. Due to the failure of the urea cycle, excessive ammonia also accumulated, negatively impacting the immune cells’ ability to combat cancer.
- Blocking an essential protein:
- Metabolic changes coincided with the infiltration of immune cells into the livers of mice.
- As cancer progressed, neutrophils and monocytes, types of white blood cells, accumulated in the livers.
- This accumulation hindered the production of a crucial protein called HNF4-alpha, responsible for regulating metabolic processes.
- It also reduced the production of albumin, a protein that prevents swelling and leakage from blood vessels.
- Effects of protein depletion:
- Decreased levels of HNF4-alpha and albumin in the liver led to weight loss in the mice.
- Gene therapy intervention:
- Scientists utilized gene therapy to restore the production of HNF4-alpha in the mice’s livers.
- Restoring HNF4-alpha resulted in:
- Cessation of weight loss in the mice.
- Shrinkage of tumors.
- Improved survival rates for the mice.
Predicting risk:
- Erez emphasizes the potential of gaining deeper insights into how cancer alters central metabolic processes from the early stages of the disease.
- This understanding, combined with the ongoing advancement of genetic treatments targeting these alterations, holds promise for the development of new therapies for early-stage cancer patients.
- The researchers devised a diagnostic model that utilizes a blood test to analyze albumin levels and other liver-related biochemical parameters.
- Applying this model to extensive datasets of cancer patients, they discovered a connection between the liver profile measured in the early stages of the disease and the subsequent risk of developing the wasting syndrome and even mortality.
- The study involved collaboration among several institutions, including the Weizmann Institute, Tel Aviv University, Hebrew University, Sheba Medical Center, Tel Aviv Sourasky Medical Center, Hadassah Medical Center, Clalit Health Services, and the participation of Prof. Joo Sang Lee from Sungkyunkwan University, South Korea.