Stress is carcinogenic and promotes metastases; blocking cortisol stops this process
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Over the last couple of years I posted several times about studies demonstrating that stress from surgery, chemotherapy or radiation (aka “cut, poison, burn” therapy) has a promoting effect on cancer growth. Unfortunately, all those studies have been either completely ignored by mainstream medicine or dismissed as only applicable to certain aggressive types of cancer (e.g. triple negative breast cancer), which grow/spread fast anyways and thus the contribution of the iatrogenic stress is very minor in comparison. Putting iatrogenic stress from medical procedures aside, chronic stress of general environmental origin has long been suspected as playing a role in cancer development, but the connection has always been dismissed by oncology as being, at best, a facilitator after tumor appearance, and definitely not a cause. The study below begs to disagree and demonstrates that chronic stress (even when mild) not only initiates the cancerization process and makes a healthy tissue begin to exhibit the structural and metabolic markers of cancer, but directly enables and drives the metastatic process as well. All of these effects of chronic stress were directly mediated by cortisol. Thus, removing the glucocorticoid receptor (GR) made the animals completely resistant to metastases after primary tumors has already formed in their bodies, and also prevented the cancerization process initiated by cortisol in healthy tissue. So, there we have it in plain view – chronic stress kills by causing cancer and fueling its spread. Also, one of the most widely prescribed classes of drugs worldwide – bioidentical/synthetic glucocorticoids – are non-mutagenic carcinogens! Since glucocorticoids are prescribed in virtually all forms of cancer (to “tame inflammation”, which is ironic considering that cortisol actually promoted inflammation) it is probably not far-fetched to say that most cancer deaths are iatrogenic. In addition, most newly diagnosed cancer cases are not only completely preventable but can probably also be classified as iatrogenic given the mantra espoused by most doctors that regular endurance exercise (which reliably ups baseline cortisol levels) is the best thing for our health ever discovered.
Now, since removing the GR completely is obviously not something feasible (or even desirable) in humans, the main focus on cancer prevention should be limiting chronic stress exposure. In fact, the study authors themselves say in the popular press article below that stress reduction should be practiced for both preventing and treating cancer. And since in this day and age stress avoidance is next to impossible, other remedies with anti-cortisol effects must be considered. The drug RU486 is the drug of choice clinically for blocking the GR. However, it is prescription-only, expensive and largely unavailable due to the politicization of its role as the “abortion pill”. Natural substances with anti-cortisol effects include aspirin, progesterone, DHEA, pregnenolone, emodin, vitamin A/D, gelatin/glycine, moderate doses niacinamide, etc.
https://doi.org/10.1016/j.ccell.2024.01.013
“…Chronic stress is associated with increased risk of metastasis and poor survival in cancer patients, yet the reasons are unclear. We show that chronic stress increases lung metastasis from disseminated cancer cells 2- to 4-fold in mice. Chronic stress significantly alters the lung microenvironment, with fibronectin accumulation, reduced T cell infiltration, and increased neutrophil infiltration. Depleting neutrophils abolishes stress-induced metastasis. Chronic stress shifts normal circadian rhythm of neutrophils and causes increased neutrophil extracellular trap (NET) formation via glucocorticoid release. In mice with neutrophil-specific glucocorticoid receptor deletion, chronic stress fails to increase NETs and metastasis. Furthermore, digesting NETs with DNase I prevents chronic stress-induced metastasis. Together, our data show that glucocorticoids released during chronic stress cause NET formation and establish a metastasis-promoting microenvironment. Therefore, NETs could be targets for preventing metastatic recurrence in cancer patients, many of whom will experience chronic stress due to their disease.”
“…Now, He and Egeblad may have reached a breakthrough in understanding exactly that. Working with CSHL Professor Linda Van Aelst, they discovered that stress causes certain white blood cells called neutrophils to form sticky web-like structures that make body tissues more susceptible to metastasis. The finding could point to new treatment strategies that stop cancer’s spread before it starts. The team arrived at their discovery by mimicking chronic stress in mice with cancer. They first removed tumors that had been growing in mice’s breasts and spreading cancer cells to their lungs. Next, they exposed the mice to stress. What He observed was shocking. Egeblad recalls: “She saw this scary increase in metastatic lesions in these animals. It was up to a fourfold increase in metastasis.” The team found that stress hormones called glucocorticoids acted on the neutrophils. These “stressed” neutrophils formed spider-web-like structures called NETs (neutrophil extracellular traps). NETs form when neutrophils expel DNA. Normally, they can defend us against invading microorganisms. However, in cancer, NETs create a metastasis-friendly environment.”
“…To confirm that stress triggers NET formation, leading to increased metastasis, He performed three tests. First, she removed neutrophils from the mice using antibodies. Next, she injected a NET-destroying drug into the animals. Lastly, she used mice whose neutrophils couldn’t respond to glucocorticoids. Each test achieved similar results. “The stressed mice no longer developed more metastasis,” He says. Notably, the team found that chronic stress caused NET formation to modify lung tissue even in mice without cancer. “It’s almost preparing your tissue for getting cancer,” Egeblad explains. To Van Aelst, the implication, though startling, is clear. “Reducing stress should be a component of cancer treatment and prevention,” she says. The team also speculates that future drugs preventing NET formation could benefit patients whose cancer hasn’t yet metastasized. Such new treatments could slow or stop cancer’s spread, offering much-needed relief.”
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@haidut Great post, I wonder if clonidine could potentially be useful here.