Good news! Cancer is history (soon)!
"Highlights
- Cachexia, a syndrome marked by unwanted weight loss, sickness, and loss of appetite that accompanies and amplifies chronic illness, affects roughly half of all cancer patients and is responsible for a quarter of all cancer deaths
- ... discovers that some lung cancer tumors can induce cachexia by communicating directly with the brain using a lipid signaling molecule—hijacking the nervous system and impacting behavior
- Findings suggest that tumors affect the peripheral nervous system and dietary changes could be used to treat cachexia and improve outcomes in lung cancer patients
...
According to the Cleveland Clinic, a quarter of cancer deaths can be attributed to one source: cachexia. ...
The researchers found that a common genetic subset of lung cancer is more prone to cachexia and that tumors from this subtype talk to the brain through sensory neurons in the lung.
Silencing these sensory nerves to disrupt the tumor-to-brain connection reduced cachexia, as did blocking the production of the lipid signaling molecule prostaglandin E2 (PGE2) through dietary changes. ..."
From the abstract of the perspective:
"Cachexia—a progressive loss of body mass despite adequate nutrition—is one of the most devastating consequences of cancer.
However, its causes are incompletely understood. Increased energy expenditure can contribute to cachexia, but “sickness behaviors,” such as loss of appetite (anorexia), fatigue, reduced activity, and malaise, also often play a part.
Several tumor-derived inflammatory molecules act on the brain and peripheral tissues to promote cachexia in some contexts , but targeting these factors has not yet led to effective cachexia treatments.
On page 90 of this issue, Cross et al. report that mouse lung tumors bearing mutations in serine/threonine kinase 11 (Stk11, also known as Lkb1) activate vagal sensory neurons through local inflammatory lipid signaling.
Notably, a high-fat diet intensifies these sensory nerve signals from the tumor to modulate the brain circuits that control feeding behavior. This mechanism promotes anorexia and cachexia."
From the editor's summary and the abstract:
"Editor’s summary
Cancer cachexia is a complex metabolic syndrome marked by reduced appetite, weight loss, and muscle wasting. Cross et al. report that a subset of Lkb1-mutant lung cancers is prone to cachexia ... When mice were fed a high-calorie, high-fat diet, reduced appetite and weight loss were observed, which was associated with reduced appetite sensing to the brain.
Prostaglandin E2 (PGE2) is a lipid-signaling molecule produced by tumors that increases when animals consume fat.
The authors found that PGE2 acts locally in the lung to drive decreased weight and appetite.
Blocking either PGE2 production or silencing sensory nerves reduced cachexia, suggesting that the peripheral nervous system may represent a therapeutic target. The observations further suggest that tumors can trigger cachexia through local nerve signaling, as opposed to only circulating factors. ...
Abstract
Sickness behaviors are common in cancer-associated cachexia and affect up to half of lung cancer patients.
We demonstrate that among the most common cancer mutations, loss of liver kinase B1 (Lkb1) promotes the development of cachexia in preclinical models of lung cancer.
In an effort to improve caloric intake with an obesogenic high-fat diet, we paradoxically observed worsened cachexia-associated sickness.
We found that local production of prostaglandin E2 (PGE2), rather than circulating factors, promotes sickness and that genetic, dietary, and pharmacological inhibition of tumor-derived PGE2 suppresses sickness and cachexia.
Notably, we demonstrate that lung sensory neuron abrogation prevents PGE2-dependent cachexia.
Our study establishes localized tumor-derived signals to sensory neurons, rather than circulating factors, as drivers of cachexia and highlights a previously unknown role of the peripheral nervous system in cancer cachexia."
Local signals, systemic decline (Perspective, no public access) "A high-fat diet affects tumor-to-nerve signaling and promotes cachexia in mice"
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