Crippling cancer stem cells and senescent cancer cells

Background:

Have you ever questioned why people die from cancer? It boils down to metastasis, treatment resistance, and cancer relapse, all of which are chiefly mediated by cancer stem cells (CSCs). Many experts believe that the successful eradication of CSCs could revolutionize the treatment of cancer.

Cancer stem cells:

These cells generally represent just 1% to 3% of all cells in a tumor, but they are the only cells with the ability to regenerate malignant cells and fuel the growth and spread of cancer. CSCs are also known as tumor-initiating cells (TICs) and tumor-survival cells (TSCs). Not only are CSCs the main driver of distant metastasis, resistance to apoptosis (cell death), treatment failure, and disease recurrence, but CSCs may also be the root cause of the original tumor itself. Because of the numerous and robust survival mechanisms of CSCs, chemotherapy, radiation, and surgery are unable to kill them. In fact, conventional therapy can do the exact opposite and stimulate the proliferation and aggressiveness of CSCs.

CSCs can migrate and nest in various areas of the body and remain dormant for months, years, or even decades until the right stimulus comes along and awakens them. While conventional therapy can eradicate the bulk (main) tumor cells, sooner or later, lingering CSCs can form new and often more aggressive tumors from a small number of cells (as few as 100). In other words, being “tumor-free” is not the same as being “cancer-free.” Eradicating the bulk tumor cells is not enough. CSCs must also be eradicated to achieve a more durable tumor response and greater long-term survival.

Senescent cancer cells:

Not all proliferating cancer cells can be forced into apoptosis when treated with chemotherapy. Instead of dying, many cancer cells simply stop proliferating, come to a standstill, and enter a senescent or dormant-like and apoptosis-resistant state. This is called senescence-associated growth arrest (SAGA), and while it sounds good, it is accompanied by something bad called senescence-associated secretory phenotype (SASP) in which the senescent cancer cells secrete copious amounts of pro-inflammatory molecules, protein-degrading compounds, and cancer-promoting growth factors. Just like a single moldy fruit can ruin an entire bowl of fruit, the harmful compounds emanating from senescent cancer cells can cause neighboring normal cells to become malignant. They can also promote the adverse effects of treatment and the proliferation of cancer stem cells, which can repopulate the tumor with new cancer cells leading to treatment failure or inevitable cancer recurrence after remission.

Many chemotherapy drugs act as “senogenic” agents, meaning, they induce senescence in cancer cells. However, when combined with “senolytic” drugs, meaning, repurposed drugs shown to eradicate senescent cells, scientists found this to be a novel and powerful “one-two punch” to quickly eradicate cancer cells. In other words, using chemotherapy to kill cancer cells and create a population of senescent cancer cells, then killing the senescent cells by using senolytic drugs. One promising senolytic drug that is readily available is digoxin.

Treatment protocol overview:

The synergistic protocol is designed to cripple cancer by eradicating proliferating cancer cells, cancer stem cells, and senescent cancer cells, all while keeping the pill burden low and the treatment tolerability high. It centers around twice-weekly, intravenous, low-dose chemotherapy. This is combined with intravenous salinomycin and resveratrol, radiofrequency hyperthermia, and oral 2-deoxy-D-glucose (2DG; liquid), dichloroacetate (DCA; liquid), digoxin (tablet), metformin (tablet), pro-resolving mediators (capsule), quercetin (liquid), reishi spore oil (capsule), and sulforaphane (capsule):

Low-dose chemotherapy, methioninase, and reishi spore oil induce apoptosis of proliferating cancer cells.
2DG, hyperthermia, reishi spore oil, resveratrol, salinomycin, and sulforaphane promote chemosensitivity and inhibit apoptosis resistance, thereby permitting lower dose chemotherapy and thus reducing or avoiding systemic toxicity. The toxic effects of chemotherapy are further mitigated by reishi spore oil, resveratrol, and sulforaphane.
Salinomycin targets cancer stem cells.
Digoxin targets senescent cancer cells. Note: Digoxin toxicity is avoided by using intermittent, low-dose digoxin.
2DG, DCA, metformin, pyrvinium pamoate, resveratrol, and sulforaphane enhance the anti-cancer effects of salinomycin.
Sulforaphane enhances the anti-cancer effects of resveratrol and inhibits hypoxia-inducible factor 1-alpha (HIF-1α) which stands at the “crossroads” of cancer-driving hypoxia and inflammation.
Hyperthermia and reishi spore oil promote the immune destruction of cancer cells.
Quercetin inhibits thermotolerance (resistance to hyperthermia)
Pro-resolving mediators reduce SASP and hasten the removal of dead cancer cells by promoting macrophage phagocytosis.

Treatment cost:

The cost of treatment is broken down as follows:

Medical monitoring: $1500 per month
Twice-weekly intravenous therapy and hyperthermia: $1500 per treatment. This includes the cost of oral 2DG.
Digoxin and metformin (prescription medications): $18 per month
Supplements: Pro-resolving mediators, reishi spore oil, and sulforaphane: $200 per month

Treatment is maintained until remission or disease stabilization is achieved. This generally takes 6-9 months. Our fees are lower than what people pay in Mexico or Europe for alternative cancer treatment. Clinics there typically charge $28,000 to $80,000 for the first month of treatment (click here and scroll down to FAQs and click “What are the costs of stage 4 cancer treatments at a clinic?”). Because many of those Mexican and European clinics lack a deeper understanding of the complex biology of cancer, they can put patients at risk by failing to target key survival mechanisms of cancer.

Monitoring treatment progress:

To verify the protocol is working as quickly as possible, we get a baseline PET/CT scan and follow-up scans every 1-3 months. If your insurance or Medicare plan does not cover the cost of the PET/CT scan, by going through RadiologyAssist.com, the discounted out-of-pocket cost ranges from $1300 to $2500, depending on where you live.

For more information:

To understand the science behind the above protocol, please study the references below:

Aghaee F, Pirayesh Islamian J, Baradaran B. Enhanced radiosensitivity and chemosensitivity of breast cancer cells by 2-deoxy-d-glucose in combination therapy. J Breast Cancer. 2012 Jun;15(2):141-7.

Balamurugan K. HIF-1 at the crossroads of hypoxia, inflammation, and cancer. Int J Cancer. 2016 Mar 1;138(5):1058-66.

Calcabrini C, Maffei F, Turrini E, Fimognari C. Sulforaphane Potentiates Anticancer Effects of Doxorubicin and Cisplatin and Mitigates Their Toxic Effects. Front Pharmacol. 2020 May 1;11:567.

Cao Y, Xu X, Liu S, Huang L, Gu J. Ganoderma: A Cancer Immunotherapy Review. Front Pharmacol. 2018 Oct 25;9:1217.

Castro-Vega LJ, Jouravleva K, Ortiz-Montero P, Liu WY, Galeano JL, Romero M, Popova T, Bacchetti S, Vernot JP, Londoño-Vallejo A. The senescent microenvironment promotes the emergence of heterogeneous cancer stem-like cells. Carcinogenesis. 2015 Oct;36(10):1180-92.

Cavuoto P, Fenech MF. A review of methionine dependency and the role of methionine restriction in cancer growth control and life-span extension. Cancer Treat Rev. 2012 Oct;38(6):726-36.

Chang CJ, Chen YY, Lu CC, Lin CS, Martel J, Tsai SH, Ko YF, Huang TT, Ojcius DM, Young JD, Lai HC. Ganoderma lucidum stimulates NK cell cytotoxicity by inducing NKG2D/NCR activation and secretion of perforin and granulysin. Innate Immun. 2014 Apr;20(3):301-11.

Cocetta V, Quagliariello V, Fiorica F, Berretta M, Montopoli M. Resveratrol as Chemosensitizer Agent: State of Art and Future Perspectives. Int J Mol Sci. 2021 Feb 19;22(4):2049.

Crezee J, Franken NAP, Oei AL. Hyperthermia-Based Anti-Cancer Treatments. Cancers (Basel). 2021 Mar 12;13(6):1240.

Demaria M, O’Leary MN, Chang J, Shao L, Liu S, Alimirah F, Koenig K, Le C, Mitin N, Deal AM, Alston S, Academia EC, Kilmarx S, Valdovinos A, Wang B, de Bruin A, Kennedy BK, Melov S, Zhou D, Sharpless NE, Muss H, Campisi J. Cellular Senescence Promotes Adverse Effects of Chemotherapy and Cancer Relapse. Cancer Discov. 2017 Feb;7(2):165-176.