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Triple Negative Breast Cancer (TNBC) Research Support Notes for Cancer Stem Cells and Chemo-resistance
Don't overlook the idea of getting out in front of treatment resistance.My notes for combating Cancer Stem Cells and Chemotherapy Resistance in Triple-Negative Breast Cancer.
Note: If you are concerned about treatment resistance for another cancer type, still use this article as a starting point; no doubt there will be crossovers, and it will speed up your study time.
If I were in treatment for Triple Negative Breast Cancer (TNBC), I would be very actively involved in supporting the standard of care treatment choices offered by my doctors. We all know it’s an aggressive breast cancer type that today’s standard-of-care oncologists struggle to manage well with only standard-of-care treatments at their disposal.
Over the years, I have observed that TNBC patients who engage with integrative oncology support are the ones experiencing the most successful treatment outcomes. If I had to do chemo, I would look for low-dose chemo options, natural compounds and high-dose IV-C.
| 1) I would need to ensure my cancer stem cells were not surviving the chemotherapy treatment as they are known to do. Ref: | |
| https://cdrjournal.com/article/view/3880 | |
| 2) I would need to ensure the targeted cancer cells did not become chemotherapy-resistant as they do. | |
| https://europepmc.org/article/pmc/pmc9456313 | |
| 3) I would need to concentrate my efforts on helping the chemotherapy do what it was intended to do as fast and effectively as possible while protecting my healthy cells from as much damage as possible. | |
| https://www.mdpi.com/2073-4409/8/9/957# | |
| 3a) Read over: "Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge | |
| The evidence presented in this review outlines the role of crucial pathways in TNBC survival following chemotherapy treatment. It highlights the importance of using combinatorial drug strategies and incorporating biomarkers in clinical studies.” | |
| https://www.mdpi.com/2073-4409/8/9/957# | |
| I read it and took notes - see below. |
TGF-β |
|
| TGF-β plays a vital role in triple-negative breast cancer (TNBC) drug resistance through regulating stemness, EMT and apoptosis | |
| https://pubmed.ncbi.nlm.nih.gov/29792857/ | |
| Liposomal Baicalein 400mg, Liposomal Berberine 250mg & Quercetin 350mg with Bromelain. | |
| 1 gram in total of bioavailable TGFb inhibitors, 2-3 times each day | |
| Baicalin and baicalein inhibit transforming growth factor-β1-mediated epithelial-mesenchymal transition in human breast epithelial cells | Read Article |
| Berberine Suppresses Cell Motility Through Down-regulation of TGF-β1 in Triple Negative Breast Cancer Cells | Read Article |
| Quercetin: A review on anti-cancer properties of Quercetin in breast cancer | Read Article |
| Bromelain | Read Article |
| What I would take: | |
| Baicalein Liposomal MCS formulas400mg (2caps), 2-3 x each day | |
| Berberine Liposomal MCS formulas250mg (1 cap) 2-3 x each day | |
| Quercetin with Bromelain MCS Formulas 350mg Quercetin + 50mg Bromelain(1 cap) 2-3 x day | |
Wnt/β-catenin: |
|
| Countering Triple Negative Breast Cancer via Impeding Wnt/β-Catenin Signaling, a Phytotherapeutic Approach | |
| https://www.mdpi.com/2223-7747/11/17/2191 | |
| Baicalein Liposomal 400mg, Curcumin Liposomal, 750mg Quercetin 350mg with Bromelain 50mg | |
| 1.55 gram in total of Wnt/β-Catenin inhibitors, 2-3 times each day | |
| Baicalein exposure promoted the downregulation of Wnt1, β-catenin in the MDA-MB-231 cells and tumour-bearing mice. | Read Article |
| The Potential of Natural Products in the Treatment of Triple-negative Breast Cancer | Read Article |
| Quercetin: The Potential of Natural Products in the Treatment of Triple-negative Breast Cancer | Read Article |
| What I would take. Everything is already listed above, so I'm covered | |
| Curcumin Liposomal MCS formulas750mg (3 caps) 2-3 x each day | |
| Baicalein Liposomal MCS formulas 400mg (2caps), 2-3 x each day | |
| Quercetin with Bromelain MCS Formulas 350mg Quercetin + 50mg Bromelain(1 cap) 2-3 x day | |
Hedgehog (Hh) |
|
| “The activation of the hedgehog pathway in TNBC cells led to the acquisition of drug resistance due to the upregulation of ABC transporters” | |
| https://pubmed.ncbi.nlm.nih.gov/23508962/ | |
| Sulforaphane 750mg, Mebendazole 100mg and Liposomal Curcumin 750mg | |
| 1.6 gram in total of Wnt/β-Catenin inhibitors, 2-3 times each day for Sulf & Curc but 1 x day for Mbz | |
| Sulforaphane Interferes with Human Breast Cancer Cell Migration and Invasion Through Inhibition of Hedgehog Signalling | Read Article |
| Repurposing the Anthelmintic Mebendazole as a Hedgehog Inhibitor | Read Article |
| In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival." | Read Article |
| Curcumin inhibits the invasion and metastasis of triple negative breast cancer via Hedgehog/Gli1 signaling pathway | Read Article |
| What I would take. Curcumin is already listed above so I'm covered with that 1 of 3 listed. | |
| Curcumin Liposomal MCS formulas750mg (3 caps) 2-3 x each day | |
| Sulforaphane MCS Formulas750 mg Sulforaphane Glucosinolate (2 caps twice daily) | |
| Mebendazole; I would do 100mg a day a week on week off or 4 days on 3 off found over the counter at local Chemists (in Australia). Study support group members can find the Mebendazole thread in the A-Z list here. | |
PI3K/Akt/mTOR |
|
| Countering Triple Negative Breast Cancer via Impeding Wnt/β-Catenin Signaling, a Phytotherapeutic Approach | |
| https://www.mdpi.com/2223-7747/11/17/2191 | |
| Curcumin Liposomal 750mg, Omega-3 DHA 700 1000mg , High Dose Melatonin 180mg and Fisetin Pro Liposomal 150mg | |
| 2.8 grams in total of Wnt/β-Catenin inhibitors, 2-3 times each day | |
| Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation | Read Article |
| The Effect of Omega-3 Polyunsaturated Fatty Acid Supplementations on Anti-tumour Drugs in Triple Negative Breast Cancer | Read Article |
| Melatonin- invest in long-term use and consistent high doses inhibit TGFb (see top of page) PI3K/Akt/mTOR and Hypoxia (and so much more) An updated review of mechanistic potentials of melatonin against cancer: pivotal roles in angiogenesis, apoptosis, autophagy, endoplasmic reticulum stress and oxidative stress | Read Article |
| Fisetin Inhibited Growth and Metastasis of Triple-Negative Breast Cancer by Reversing Epithelial-to-Mesenchymal Transition via PTEN/Akt/GSK3β Signal Pathwa | Read Article |
| What I would take. Curcumin is already listed above so I'm covered with that one of 3 listed. | |
| Curcumin Liposomal MCS formulas750mg (3 caps) 2-3 x each day | |
| Omega-3 DHA 700 from California Gold on iherb1000MG (1 cap) 2-3 x each day | |
| Melatonin: PureBulk.com | |
| Fiseten Liposomal MCS Formulas300mg (2 caps) 2-3 x day | |
PTEN |
|
| The same article points to how the loss of PTEN, the tumour suppressor gene, upregulates PI3K/Akt/mTOR. | |
| https://www.mdpi.com/2223-7747/11/17/2191 | |
| The good news is that Baicalein Sulforaphane, Aswagandha, Curcumin, Omega 3 DHA, and Quercetin all up-regulate PTEN expression. | |
| All these supplements are listed in the notes above so we are covered. | |
| Baicalein up-regulates PTEN expression. | Read Article |
| Sulforaphane induces autophagy by inhibition of HDAC6-mediated PTEN activation in triple-negative breast cancer cells | Read Article |
| Ashwagandha: Effects and mechanisms of dietary bioactive compounds on breast cancer prevention | Read Article |
| Curcumin: Flavonoids and Other Polyphenols Act as Epigenetic Modifiers in Breast Cancer | Read Article |
| Omega-3 Fatty Acid Treatment Combined with Chemotherapy to Prevent Toxicity, Drug Resistance, and Metastasis in Cancer | Read Article |
| Quercetin: Synthesis and in vitro anticancer evaluation of novel flavonoid-based amide derivatives as regulators of the PI3K/AKT signal pathway for TNBC treatment | Read Article |
| All these supplements are listed in the notes above so we are covered. | |
NF-kBSignalling |
|
| "..the level of NF-κB expression in TNBC is several times higher than normal breast tissue. It is well established that NF-κB activation mediates chemoresistance in breast and other types of cancer." Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge. 2019. | |
| https://www.mdpi.com/2073-4409/8/9/957# | |
| https://pubmed.ncbi.nlm.nih.gov/28388298/ | |
| Curcumin Liposomal 750mg, Andrographolide 80mg, Omega-3 DHA 700 1000mg , | |
| approx 1.8 grams in total of NF-κB inhibitors, three times each day | |
| Curcumin Targeting NF-κB/Ubiquitin-Proteasome-System Axis Ameliorates Muscle Atrophy in Triple-Negative Breast Cancer Cachexia Mice | Read Article |
| Modulation of Inflammatory Cytokines by Omega-3 Fatty Acids | Read Article |
| Andrographolide suppresses the malignancy of triple-negative breast cancer by reducing THOC1-promoted cancer stem cell characteristics. | Read Article |
| What I would take. Curcumin and Omega-3 are already listed above so I'm covered with 2 of the 3 listed. | |
| Curcumin Liposomal MCS formulas750mg (3 caps) 2-3 x each day | |
| Omega-3 DHA 700 from California Gold on iherb | |
| Andrographis each capsules contain 80mg of Andrographolides | |
JAK/STAT |
|
| "STAT3, a member of the JAK/STAT signalling pathway, is highly expressed in TNBC and connected with tumour initiation, aggressive clinical behaviour, unfavourable outcome, and resistance to chemotherapy. STAT3 interacts and collaborates with NF-kB, leading to chemoresistance in TNBC. In addition, STAT3 was upregulated in TNBC stem cells resistant to doxorubicin. Mechanisms of Chemotherapy Resistance in Triple-Negative Breast Cancer—How We Can Rise to the Challenge. 2019. | |
| https://www.mdpi.com/2073-4409/8/9/957# | |
| https://pubmed.ncbi.nlm.nih.gov/28388298/ | |
| Curcumin Liposomal 750mg, EGCG 348mg, Quercetin 350mg with Bromelain 50mg | |
| approx 1.5gram in total of JAK/STAT inhibitors, 3 times each day | |
| Curcumin Modulates Key Molecular Signaling Pathways in Hormone-Independent Breast Cancer | Read Article |
| Quercetin and EGCG exhibit chemopreventive effects in cholangiocarcinoma cells via suppression of the JAK/STAT signalling pathway | Read Article |
| What I would take. Curcumin and Quercetin is already listed above so I'm covered with 2 of of 3 listed. | |
| Curcumin Liposomal MCS formulas750mg (3 caps) 2-3 x each day | |
| Andrographiseach capsules contain 80mg of Andrographolides | |
Hypoxia HIF-1a |
|
| "TNBC more often presented HIF-1α expression (43.2%) than non-TNBC (35.2%). TNBC subgroup demonstrated a significant correlation between HIF-1α expression and tumour size (pT1–pT4) (p = 0.021), which may suggest that HIF-1 alpha expression in this group of patients may be an additional and significant marker in the evaluation of the advance of the disease, affecting therapeutic decisions. | |
| https://www.intechopen.com/chapters/60171 | |
| Danshen 750mg, Andrographolide 80mg and Betulinic Acid Liposomal 1000mg, High-dose Melatonin 60mg | |
| approx 1.8 grams in total of HIF-1a inhibitors, 3 times each day | |
| T2A from Danshen inhibited the angiogenesis and growth of human breast cancer xenografts in nude mice through suppression of HIF-1α and VEGF. | Read Article |
| The Efficacy of Andrographolide and its Combination with Betulinic Acid in the Treatment of Triple Negative Breast Cancer | Read Article |
| Melatonin, FUNDC1, acts as an activator of hypoxia-induced mitophagy. Findings indicated that melatonin inhibits TNBC progression via the lnc049808/miR-101/FUNDC1 axis and that melatonin may serve as an alternative therapy for TNBC. | Read Article |
| What I would take as well as Melatonin. | |
| Danshen MCS formulas 1500mg (3 caps) 2-3 x each day | |
| Danshen also inhibits: PI3K/Akt, MAPK and JAK/STAT3, | |
| Betulinic Acid MCS Formulas 1000 mg (2 caps) 3 x each day | |
|
Andrographiseach capsules contain 80mg Andrographolides (1 cap) 3 x each day NotchNotch Signalling Activation as a Hallmark for Triple-Negative Breast Cancer Subtypewww.hindawi.com/journals/jo/2019/8707053/ Liposomal Curcumin 750mg, Ashwagandha 400mg & Ginger 500mg Curcumin Article: The Potential of Natural Products in the Treatment of Triple-negative Breast CancerRead Article 6-Shogaol suppresses the growth of breast cancer cells by inducing apoptosis and suppressing autophagy via targeting notch signalling pathwayRead Article Ashwagandha: Withaferin A inhibits in vivo growth of TNBC breast cancer cells accelerated by Notch2 knockdownRead Article Unlike Notch-1 and 4, the Notch-2 receptor seems to be connected to improved patient clinical outcome.Read Article What I would take: |
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DISCLAIMER: Any and all information in this post was gathered from published research in cell lines or animals, or from typical clinical use. It may not be complete, may not have not been verified in humans, and is NOT meant or given as medical advice, but only as a guide to further exploration.
