Ivermectin Defeats Drug Resistance in Cancer Cells via the EGFR/NFkB Pathway
Ivermectin Defeats Drug Resistance in Cancer Cells via the EGFR/NFkB Pathway
2019 Study Highlights IVM Cancer Treatment Benefits
In June 2019, well before anyone had heard of COVID-19, a Chinese group of researchers wrote about the massive anti-cancer benefits of Ivermectin, a drug which at that moment in time, enjoyed an untarnished reputation of safety and excellence in treating parasitic diseases. Moreover, IVM could also be repositioned for a role in cancer treatment.
Why is this important?
Because 90% of cancer deaths are related to drug resistance.
If we could defeat drug resistance, we could defeat cancer. If we could consistently restore cancer drug sensitivity by adding a repurposed medication like Ivermectin, we could change the world.
Dr. Lu Jiang and colleagues were the first to show that Ivermectin could reduce or eliminate multi-drug resistance in cancer treatment in vivo - that is in a living organism. While many studies can show an effect against cancer cells in a test tube or in vitro, it is far more significant to show a benefit in the human being or the living animal.
The research team found that Ivermectin could powerfully reverse chemotherapy drug resistance specifically by blocking the EGFR pathway which could improve cancer treatment outcomes.
First, let us review why EGF - epidermal growth factor - is so crucial to control if we are to cure cancer. EGF and its receptor EGFR strongly promote metastasis and cancer spread.
“Along with sustaining cell proliferation and conferring resistance to anti-cancer cytotoxic drugs, EGFR strongly promotes metastasis through a large collection of paracrine loops, each controlling a critical step of the metastasis cascade. In the last few years, we learned that diverse non-coding RNAs, including microRNAs, and circular RNAs, play unexpectedly complex regulatory functions in EGFR signaling.”
In this PubMed study, the EGFR pathway is highly involved in metastasis formation and can be triggered by multiple epigenetic factors including microRNA.
As a brief review, epigenetics involves how behaviors and the environment can alter the way genes work, turning them "on" and "off". Dr. Peter McCullough recently discussed epigenetics in an interview. In addition to preventing or causing disease, epigenetics can help one look younger or older than one’s biological age.
Dr. McCullough noted that he had completed a marathon in each of the 50 United States in the course of eight years. He then asked the question of whether exercise in some cases might be so much that it promotes rather than diminishes aging. And the answer is yes [25:30]. I covered exactly this point in my 2019 Coffee Cure book.
Naturally, one can have the benefit of more favorable epigenetics through positive lifestyle and environmental influences, or conversely more unfavorable ones through the opposite. Think of beneficial choices of walking an hour per day for twenty years versus smoking 2 packs per day for a decade. However, the negative epigenetic effects on health of certain recent injections are just now coming to light.
Epigenetic modifications of DNA have long been known to cause cancer. The three main mechanisms of epigenetic modification are
non-coding RNAs
histone modification
DNA methylation
Dr. William Makis has written about the microRNAs associated with mRNA vaccines which he considers oncogenic. Makis and others have written about the recent emergence of Turbo Cancers [10:21].
It is known that circular RNA, non-coding RNA, and microRNA are epigenetically associated with cancer through their effect on EGF and EGFR.
Jiang and colleagues wrote about Ivermectin’s anti-cancer actions in reversing chemotherapy drug resistance via the EGFR pathway. They showed that Ivermectin directly binds to EGFR to re-establish chemotherapy sensitivity.
The authors noted that EGFR drug resistance plays a major role in breast and prostate cancer. Thus, reversing this can be a game changer.
The degree of this change with IVM was noteworthy. In their study, Jiang and colleagues looked at vincristine-resistant colorectal cancer, Adriamycin-resistant breast cancer, and finally Adriamycin-resistant chronic myeloid leukemia. They selected these cancers because colorectal and breast are among the most common solid malignant tumors and chronic myeloid leukemia is one of the most common malignant blood cancers.
The addition of Ivermectin increased the sensitivity of Adriamycin in resistant tumor cells by a factor of 49.
The researchers used a dose of 2.0mg/kg with the mice in their study and they note this is equivalent to what most humans are prescribed for parasites. I would respectfully add that in my experience, the standard human dose of Ivermectin for scabies, for example, is closer to 0.2mg/kg.
“However, in our study, it is the first time to show that IVM could reverse multidrug resistance of cancer cells in vivo. Moreover, the dose (2 mg/kg body weight, i.p.) we used in the mice was lower than those used to directly inhibit tumor growth. Furthermore, the dose of 2 mg/kg was shown to be approximately corresponding to what is given as an anthelmintic agent in humans [17, 41].”
The importance of EGFR in triggering and maintaining cancer growth cannot be overstated. EGFR is a foundational member of several growth factor receptors with a common mechanism - tyrosine kinase. Others include its preferred heterodimer, HER2/ERBB2 common to breast cancer. An abundance of EGFR and related mutations are seen in brain and lung tumors.
Thus, many drugs - tyrosine kinase inhibitors - have been developed to target EGFR. These TKIs include lapatinib and Sorafenib. TKI’s - although often being referred to as a magic bullet - almost always suffer the same fate of development of rapid drug resistance.
“Thus, despite the availability of several EGFR-specific TKIs, the long-term efficacy of these drugs is limited by multiple routes of acquired resistance.”
A recent study demonstrated that Ivermectin worked synergistically against Hepatocellular Carcinoma in combination with Sorafenib, a kinase inhibitor.
However, Ivermectin has anti-cancer activity well beyond its effect on EGFR and related drugs. In pancreatic cancer, it can synergize the effectiveness of Gemcitabine by its action on mTOR and STAT and on the mitochondria.
Whenever researching Ivermectin for repurposing existing drugs against cancer, I always consult with the World Authority on the subject, Dr. Paul Marik, and in particular, his Cancer Care book. I consulted with
him regarding Ivermectin and target cancers, mechanisms of action, dosage, and cautions.
Dr. Marik notes that Ivermectin has shown in vitro activity against all the following cancers - breast (including TNBC), as well as lung, stomach, cervix, esophageal, endometrium, liver, prostate, kidney, and ovarian cancer as well as cholangiocarcinoma, melanomas, leukemia, lymphoma, and gliomas.
Dr. Marik also noted a study that showed that Ivermectin reduces drug resistance through its effect on P glycoprotein. This aligns with the Jiang study that showed Ivermectin worked through the EGFR/ERK/Akt/NfkB pathway ultimately “downregulating the expression of P-gp.”
Marik notes there are multiple mechanisms of Ivermectin’s anti-cancer action including using the Akt/mTOR pathway to induce autophagy, inducing apoptosis via the mitochondria, and inhibiting the WNT pathway.
Dr. Marik discusses the optimal dose of Ivermectin for its anti-cancer effects. He writes that 12 to 18 mg per day prescribed indefinitely may be effective. In my opinion, for metastatic disease higher doses may be needed;
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