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Questions About Chemo and Repurposed Drugs


Kat B
(@kat-b)
Joined: 3 weeks ago
Posts: 2
Topic starter  

Hi,

Thanks for the great website. I have a question about using Febendazole and/or other repurposed drugs or natural substances along with chemotherapy. Also the timing of using these with chemo.

I have invasive ductal carcinoma, Grade 3, Stage 2A, triple negative. I am supposed to start the “standard of care” chemo routine this week. Paclitaxel and Carboplatin weekly X12 weeks, followed by Adriamycin and Cyclophosphamide every two weeks for 8 doses. Wait one month and have surgery, type still to be decided, awaiting genetic testing, and response to treatment.  I am going to do chemo because I am scared not to, but I believe there is so much unknown or unexplored because of modern medicine’s economic model. I would like to explore ways to enhance the effects and minimize the side effects of chemo.

I have been on a keto diet for 2 years, and successfully reversed my borderline type 2 diabetes. I was able to go off Metformin, now I learn maybe I should go back on it! Regardless, I use intermittent fasting and plan to fast 24 hours before and after chemo. The oncologist is not offering much support about considering anything other than “the standard of care.” I am sure he doesn’t have time to go over everything his patients may dig up using Google, but I’m citing PubMed articles and research.

I should add, I am 68, have hypertension well controlled on medication. I also have HHT, which I saw mentioned in one article. I’ve also read it may confer some better cancer outcome due to the “deficiency in endoglin”. I was on HRT up until they told me to stop it. (I felt much better before!)

I would love to hear any ideas or experiences that could be helpful.


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Daniel
(@daniel)
Admin
Joined: 6 years ago
Posts: 1012
 

Hi Kat,

Thank you for your question. There is a lot to say. But first here is some information that you may find relevant:

If surgery is planned:

  1. Using Chloroquine at 500mg/week (that means ~2 capsules/week) for 4 weeks will reduce the chance of metastatsis due to surgery
    1. Reference: Preventing invasive breast neoplasia with chloroquine https://cancerres.aacrjournals.org/content/77/13_Supplement/CT140
  2. Using Ketorolac prior to surgery is known to reduce cancer recurrence. It is important to discuss that with the surgeon. Watch this video https://www.youtube.com/watch?v=H8zVrYEW8vE&feature=youtu.be
    1. Potential Benefit of Intra-operative Administration of Ketorolac on Breast Cancer Recurrence According to the Patient's Body Mass Index https://www.ncbi.nlm.nih.gov/pubmed/29718396
    2. Intraoperative use of ketorolac or diclofenac is associated with improved disease-free survival and overall survival in conservative breast cancer surgery https://www.ncbi.nlm.nih.gov/pubmed/24464611
    3. Presented by Dr. Vikas P. Sukhatme: A Simple, One-Time, Inexpensive and Non-Toxic Intervention to Improve Cancer Survival https://www.youtube.com/watch?v=H8zVrYEW8vE&feature=youtu.be

Metformin and Statin

Metformin Targets Cholesterol Biosynthesis Pathway, GM1 Lipid Raft Stabilization, EGFR Signaling and Proliferation in Triple Negative Breast Cancers https://juniperpublishers.com/ctoij/pdf/CTOIJ.MS.ID.555765.pdf

Artesunate

The anti-malarial drug artesunate causes cell cycle arrest and apoptosis of triple-negative https://www.ncbi.nlm.nih.gov/pubmed/30660598/

Metformin and Hemin

Effective breast cancer combination therapy targeting BACH1 and mitochondrial metabolism https://sci-hub.tw/https://www.nature.com/articles/s41586-019-1005-x

Boswellia serrata

Plerixafor is a CXCR4 inhibitor that reduces the chance of mets to the brain. Acetyl-11-keto-b-boswellic acid (AKBA) from Boswellia serrata does that too. https://www.dovepress.com/cxcr4-in-breast-cancer-oncogenic-role-and-therapeutic-targeting-peer-reviewed-fulltext-article-DDDT Therefore using Boswellia serrata supplements with high AKBA may help reduce the chance of mets to the brain.

Doxycycline

Doxycycline, an Inhibitor of Mitochondrial Biogenesis, Effectively Reduces Cancer Stem Cells (CSCs) in Early Breast Cancer Patients: A Clinical Pilot Study   https://www.frontiersin.org/articles/10.3389/fonc.2018.00452/full

Metformin and Propranolol

Metformin and propranolol combination prevents cancer progression and metastasis in different breast cancer models https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5356849/ Taken together our results suggest that metformin plus propranolol combined treatment might be beneficial for triple negative breast cancer control, with no symptoms of toxicity.

 

Targeted treatments against TNBC:

Bicalutamide

Here is a case of a heavily pretreated woman with metastatic TNBC and AR expression who achieved a complete clinical response after 4 months of treatment with the AR antagonist bicalutamide.

According to this article and case report, complete response could be obtained in some triple negative breast cancers when the patinet is treated with a common drug used for prostate cancer called Bicalutamide. Bicalutamide is a androgen receptor antagonist and it seems that 10% to 32% of the triple negative breast cancers have androgen receptors that can be targeted by Bicatulamide.

Reference: Complete Response of Metastatic Androgen Receptor–Positive Breast Cancer to Bicalutamide: Case Report and Review of the Literature http://ascopubs.org/doi/full/10.1200/jco.2013.49.8899

Estradiol

Another form of estrogen receptor — called estrogen beta — is present in 25 percent of triple-negative tumors, as well as in over 30 percent of estrogen receptor-positive breast cancer tumors. Research showed that the estrogen receptor beta is a tumor suppressor, which correlates with better patient outcomes.

"Remarkably," claims Hawse, "we discovered that estradiol, which normally stimulates [the] growth of cancer cells in tumors that express estrogen receptor alpha, has the opposite effect in triple-negative breast cancer." https://www.medicalnewstoday.com/articles/323281.php

Here is the research paper demonstrating the anti-cancer effects of Estradiol: ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis. https://www.ncbi.nlm.nih.gov/pubmed/30257941

Mayo researchers identify potential new treatment for subset of women with triple-negative breast cancer https://newsnetwork.mayoclinic.org/discussion/mayo-researchers-identify-potential-new-treatment-for-subset-of-women-with-triple-negative-breast-cancer/

Clofazimine

Towards the first targeted therapy for triple-negative breast cancer: Repositioning of clofazimine as a chemotherapy-compatible selective Wnt pathway inhibitor https://www.ncbi.nlm.nih.gov/pubmed/30771433 Wnt signaling is overactivated in triple-negative breast cancer (TNBC) and several other cancers, and its suppression emerges as an effective anticancer treatment. However, no drugs targeting the Wnt pathway exist on the market nor in advanced clinical trials. Here we provide a comprehensive body of preclinical evidence that an anti-leprotic drug clofazimine is effective against TNBC. Clofazimine specifically inhibits canonical Wnt signaling in a panel of TNBC cells in vitro. In several mouse xenograft models of TNBC, clofazimine efficiently suppresses tumor growth, correlating with in vivo inhibition of the Wnt pathway in the tumors. Clofazimine is well compatible with doxorubicin, exerting additive effects on tumor growth suppression, producing no adverse effects. Its excellent and well-characterized pharmacokinetics profile, lack of serious adverse effects at moderate (yet therapeutically effective) doses, its combinability with cytotoxic therapeutics, and the novel mechanistic mode of action make clofazimine a prime candidate for the repositioning clinical trials. Our work may bring forward the anti-Wnt targeted therapy, desperately needed for thousands of patients currently lacking targeted treatments.

 

Others relevant:

Mebendazole Potentiates Radiation Therapy in Triple-Negative Breast Cancer https://www.redjournal.org/article/S0360-3016(18)33688-5/pdf

Auranofin - REPURPOSING AN EXISTING THERAPY FOR TRIPLE-NEGATIVE BREAST CANCER https://nbcf.org.au/research/our-research/search-our-research/improved-and-new-treatment/repurposing-an-existing-therapy-for-triple-negative-breast-cancer/

Repurposing antiretroviral drugs (Efavirenz) for treating triple-negative breast cancer via LINE-1 regulation https://openresearch-repository.anu.edu.au/handle/1885/164936

Inhibition of fatty acid oxidation as a therapy for MYC-overexpressing triple-negative breast cancer https://www.nature.com/articles/nm.4055

Honokiol (the second case report after prostate is a triple negative patient)

Intravenous Honokiol in Drug-Resistant Cancer: Two Case Reports  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7268168/

EGCG may be valuaable in TNBC: 

Current shreds of evidence on the anticancer role of EGCG in triple negative breast cancer: an update of the current state of knowledge  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954554/

EGCG is a FASN inhibitor which is relevant in TNBC  https://clincancerres.aacrjournals.org/content/22/18/4687

Baicalein & Baicalin the active components of the natural herb Scutellaria baicalensis (SB)

Baicalein induces tumor suppression in triple negative breast cancer by mTOR inhibition mediated through DDIT4 expression  https://www.journalacs.org/article/S1072-7515(12)00804-6/fulltext

Baicalin inhibits the metastasis of highly aggressive breast cancer cells by reversing epithelial-to-mesenchymal transition by targeting β-catenin signaling  https://www.spandidos-publications.com/10.3892/or.2017.6011

A phase 1B dose escalation trial of Scutellaria barbata (BZL101) for patients with metastatic breast cancer  https://pubmed.ncbi.nlm.nih.gov/20054647/

This post was modified 3 weeks ago by Daniel

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Daniel
(@daniel)
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Daniel
(@daniel)
Admin
Joined: 6 years ago
Posts: 1012
 

After going through all this info, please place the information regarding:

- chemo to be taken
- supplements and repurposed drugs that you are taking or considering taking

in to an Excel, as a time line. Each cell will represent one day, and on vertical please list the drugs and related dose planned.

You can send this to me by e-mail and I will give you my feedback regarding selected drugs and supplements, dose and timing.

Kind regards,
Daniel


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Kat B
(@kat-b)
Joined: 3 weeks ago
Posts: 2
Topic starter  

Thank you so much, Daniel. I will delve more into the articles and information. I did see the one about using PPI, Omeprazole, and started that since I have some GERD and have taken it before.

What time is it in The Netherlands? Do you ever get to sleep? 😉 

 


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Daniel
(@daniel)
Admin
Joined: 6 years ago
Posts: 1012
 

@kat-b You are very welcome Kat! I do my best with sleeping, but since I was a child I used to walk up early in the morning thinking that life happens without me while I sleep - now I try not to sleep at all 😀 Regarding PPIs I am not sure if I would take that high dose continuous but at least as pulses several days prior to chemo make very much sense since they address two major resistance mechanisms: reduce the chance for Doxorubicin protonation as well as it's lockdown in lysosomes.

Kind regards,
Daniel


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