Posted on 03/14/2022 6:14:23 PM PDT by ConservativeMind
A new study suggests that the malaria drug hydroxychloroquine inhibits pathways that drive resistance to the chemotherapy agent cisplatin in head and neck cancers and restores tumor-killing effects of cisplatin in animal models.
The findings pave the way for a clinical trial that combines cisplatin and hydroxychloroquine to treat chemotherapy-resistant head and neck cancers.
"When caring for patients with head and neck cancers, I often see chemotherapy fail. Cisplatin is a very important chemotherapy drug, but tumor resistance to cisplatin is a huge problem," said co-senior author Umamaheswar Duvvuri, M.D., Ph.D. "My lab is interested in understanding the mechanisms of resistance so that we can find better ways to treat these patients."
Previous research showed that a protein called TMEM16A is linked with cisplatin resistance in patient tumors.
The new study suggests that TMEM16A promotes expulsion of cisplatin in cellular compartments called lysosomes. In a healthy cell, lysosomes act like a recycling and waste disposal system, breaking down molecules for reuse and expelling cellular detritus.
To evaluate its potential to treat cisplatin-resistant cancers, the team first implanted human cancer cells onto the membrane surrounding the embryo in fertilized chicken eggs.
They found that eggs treated with both hydroxychloroquine and cisplatin had greater tumor cell death than those treated with cisplatin alone.
Similarly, in mice with tumors derived from cisplatin-resistant human cancer cells, the combination of hydroxychloroquine and cisplatin slowed tumor growth more than either compound alone.
"These experiments suggest that hydroxychloroquine has a synergistic effect with cisplatin," explained Duvvuri. "This is relevant for patients because repurposing hydroxychloroquine will allow us to translate these findings to the clinic much faster than we could with a novel compound."
The researchers are now designing a clinical trial to treat head and neck cancer patients with a combination of hydroxychloroquine and cisplatin.
(Excerpt) Read more at medicalxpress.com ...
Who will be incentivized to run and pay for the clinical trials if HCQ is so cheap? Where’s the return?
You’d hope NIH would do it, but they’ve lost my confidence in the past two years.
40 years too late for my Dad, but I’m happy to see any advances in this treatment-resistant type of cancer.
Ping
Covid must really be winding down if they’re willing to again sing the praises of this drug.
BKMK. ÷÷÷ HCQ
The parenthetical on the title is a little deceiving. Not sure if it was in the or original or if it was added. I am sure it was innocent of added.
The article shows that HCQ does not treat refractory CA. It does suggest that HCQ may either potentiate cisplatin. If I recall cisplatin is a rare earth alkaloid with a heavy metal. So it may stand to reason that HCQ which had a proposed MOS of being an ionophore allowing zinc fo cross the viral envelop in CoVId thereby leading to viral death did not show the results people hoped for.
However in highly metabolic cells such as CA it may be a better treatment as an adjuvant.
Interesting study to come.
I went to the actual study, and this, I believe, is where it conclusively shows it's not only “potentiating:”
Next, we established a PDX from a patient who had been treated with cisplatin-based therapy but developed treatment resistance. This PDX was found to natively express a high level of TMEM16A. We treated mice bearing this PDX with either vehicle control or cisplatin with or without HCQ, skipping the HCQ alone group because of the abundance of data indicating HCQ as a safe drug in vitro as well as CAM experiments. HCQ treatment restored sensitivity to cisplatin in this PDX (Fig. 6C), suggesting that lysosomal inhibition potentiates cisplatin toxicity in vivo. To determine cellular damage inflicted through HCQ, we used phospho-histone H2AX, a marker for DNA double-strand break. Immunohistochemistry of PDX tissue stained with pH2AX shows significantly increased positively stained bodies in the combination group, further supporting our hypothesis that HCQ sensitizes the tumor tissue to cisplatin-induced death (Fig. 6D).
Yes, it does also potentiate it, as described further below, though.
Thoughts? I always appreciate your insight.
I commend you for your knowledge and thoroughness. If I read what you included it says that the HCQ alone trial was skipped. I wish they had done it to truly see if HCQ on its own was tumor lytic. I agree potentiation may be the wrong word but it sure does look like and excellent adjuvant to therapy.
The golden age of cancer treatment is upon us with -mab (monoclonal targeted) treatment and specific genetic therapy.
Thanks for positing all you do. You add a significant amount of knowledge to our forum.
Yet another reason the “medical professionals” and Big Pharma didn’t want HCQ out there.
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I heard a talking head say that if they ever admitted there are effective treatments for Chinavirus, it would invalidate the conditions required for the Emergency Authorization of vacs.
Incidentally, I have been treated for Chinavirus TWICE now with HCQ/zith/Zn cocktail, and it worked remarkably like a CURE both times.
I had it, once, without any HCQ or ivermectin. Not fun, but hardly the end of the world. Just tired. It went into pneumonia, which antibiotics knocked out.
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Clearly, your doctor was trying to do away with you by denying you treatment.
Doctor? I don’t need no stinkin’ doctor.
Seriously, I knew it was China Virus; I didn’t have a fever; I wasn’t in any condition that would cause me to go to an ER.
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