This is an aspect that I discussed multiple times on this website, i.e. one of the important aspects to be addressed in order to increase the chance for effectiveness of immunotheraphies is the acidity around the tumors, which is there for most advanced cancer patients. Here is a post I wrote on how to address this aspect https://www.cancertreatmentsresearch.com/ph-cancer-a-top-treatment-strategy/
- June 2018: Curing cancer? Further along the new pH-centric road and paradigm
- June 2018: Visualizing the effects of metformin on tumor growth, vascularity, and metabolism in head and neck cancer
- April 2018: Drugs used for treatment of erectile dysfunction and pulmonary arterial hypertension as anti-cancer agents
A few days ago, a new paper from one of my favorite organisations (AntiCancerFunds) published a review paper on the anti cancer potential of drugs used typically for treatment of erectile dysfunction and pulmonary arterial hypertension. Example of drugs discussed in this paper are sildenafil, tadalafil, vardenafil, avanafil and udenafil. Thir anti cancer mechanisms seems to be related to one or more of the following: immune modulation (MDSC- and Treg- reduction), multi drug resistance reduction, Tumour hypoxia reduction, aromatase inhibition. Most of these actions seem to be related to the PDE5 inhibition capabilities of these drugs. As a result these drugs have been shown to be effective against multiple types of cancers in the lab such as Chronic lymphocytic leukaemia, Prostate, Colorectal, Brain, Breast, Melanoma, Multiple myeloma, Lung, Lymphoma, Liver, Head and neck, Rhabdomyosarcoma, Ehrlich ascites carcinoma. However these results were achieved in a pre-clinical setting. In humans, these drugs have been already shown to add value for patients with macroglobulinemia, penile squamous cell carcinoma, MM. Based on the evidence, the authors at AntiCancerFunds concluded the following:
“The data are strongest for clinical trials of PDE5 inhibitors, in combination with other agents, in the following cancer types (a) HNSCC (b) Glioblastoma (c) Pancreatic cancer (d) Medulloblastoma (e) Waldenstrom’s macroglobulinemia (f) Melanoma. The perioperative use of PDE5 inhibitors in combination with other perioperative therapies is also of interest in the following cancers: (a) Colorectal cancer (b) Breast cancer (c) HNSCC”
- November 2017: Statin and Bisphosphonate Induce Starvation in Fast-Growing Cancer Cell Lines
- November 2017: Mebendazole as a a safe and novel therapeutic approach for acute myeloid leukemia (AML)
A significant proportion of both pediatric and adult AML patients cannot be cured and since the upper limits of chemotherapy intensification have been reached, there is an urgent need for novel therapeutic approaches. In this context, scientist have recently found Mebendazole (a safe, cheap and over the counter drug previously discussed on this website here) as a potentially effective treatment for acute myeloid leukemia (AML)
- August 2017: approval of a patent on piperazine to treat cancer leads to share price jump of a small biotech company (an anthelminthic especially useful in the treatment of partial intestinal obstruction caused by Ascaris worms)
“Rexahn Pharmaceuticals (RNN +27.3%) is up on almost double normal volume, albeit on turnover of only 577K shares, in apparent response to the issuance of a new patent (U.S. Patent No. 9,744,167) from the USPTO covering storage-stable nanoparticulate compositions and formulations of piperazine compounds used to treat and prevent proliferative diseases, including cancer.” (Ref.)
- April 2017: Overcoming cancer treatment resistance
“Researchers have known that avoiding cross-resistance is key; this investigation tells us we also need to start considering drug holidays as well,” said Dr. Scott.
Fasting-like diet with chemotherapy strips away the guard that protects breast cancer and skin cancer cells from the immune system, according to a new USC-led study on mice. “T regulatory” cells which protect the cancer cells were expelled.
Inserted through the skin and into a vein, long-term intravascular devices such as IV catheters deliver to patients a range of life-saving medications, nutrition and fluids, among other uses. But these life-saving devices also can provide a furtive pipeline for germs from the external world to gain access to the bloodstream of patients who often already are sick, resulting in a serious infection or even death. Maki’s new approach for patients with intravascular catheters is a daily “rinse cycle” with a 25- to 50-percent solution of ethyl alcohol, or medical-grade ethanol. “We fill each lumen of the catheter with the ethanol solution and then cap it off,” says Maki. “It is allowed to sit there for an hour, rapidly killing any germs that have insidiously gained access. We then simply pull it back out and reattach the IV fluids, intraveneous nutrition or intravenous medications, and the risk of later bloodstream infection caused by germs that may have gained access in the preceding 24 hours has been essentially eliminated.”
- September 2016: Intravenous magnetic nanoparticle cancer hyperthermia
- September 2016: Caffeine acts as a negative modulator of cell proliferation
- September 2016: Albendazole as a promising molecule for tumor control
The conclusion of this study: “We propose that ABZ induces oxidative stress promoting DNA fragmentation and triggering apoptosis and inducing cell death, making this drug a promising leader molecule for development of new antitumor drugs.”
I indeed know the potential of ABZ and like it for long time, and intend to once write a post on it. It is an over the counter and FDA approved drug – an anti worm medicine, easily accessible (e.g. eBay) and cheap.
- September 2016: Fatal liver and bone marrow toxicity by combination treatment of dichloroacetate and artesunate in a glioblastoma multiforme patient. Case report and review of the literature
According to this case report there is a risk when combining DCA with Artemisinin in intravenous forms.
- August 2016: Targeting Negative Surface Charges of Cancer Cells
PIK3CA mutations reprogram glutamine metabolism in colorectal cancer, Nature Communications(2016) “In layman’s terms, we discovered that colon cancers with PIK3CA oncogenic mutations are addicted to glutamine, a particular nutrient for cancer cells. We also demonstrated that these cancers can be starved to death by depriving glutamine with drugs.”
This is a nice article published by The New York Times Magazine discussing Warburg’s discovery that was left out of textbooks altogether, and in this context cancer as a metabolic disease.
Patients receiving cancer treatment could increase their chance of survival by up to 20 percent and help stop their cancer from spreading by taking a low dose of aspirin, new research suggests.
- April 2016: 98.6 percent five-year cure rate for early stage prostate using SBRT therapy, a form of radiation therapy
This is compared to 80 to 90 percent achieved with previous techniques. In addition, “the current form of radiation is 44 treatments given over nine weeks. In contrast, the SBRT therapy we used allows the delivery of highly focused radiation in only five treatments, allowing patients to return to their normal lives more quickly”
Common cholesterol-lowering drugs could provide relief to patients suffering from a chronic lung disease, a study has shown. The drugs — known as statins — were found to help alleviate the chronic coughing associated with the disease for some patients. Statins are commonly prescribed for people at risk of heart attack because they can reduce cholesterol levels, but scientists are increasingly finding that they also have anti-inflammatory effects.
- March 2016: A top cancer doctor thinks one thing prevents us from curing 100,000 more patients every year
“The rate-limiting step in eradicating cancer today is not the science but the regulatory environment we work in,”
Researchers said those taking part in the trial were left astounded at the “mind-blowing” effect of combining two drugs – Herceptin, the current standard treatment for such cases, with a second drug called Tyverb.
- Feb 27th 2006 Penfluridol: An Antipsychotic Agent Suppresses Metastatic Tumor Growth in Triple-Negative Breast Cancer by Inhibiting Integrin Signaling Axis
Metastasis of breast cancer, especially to the brain, is the major cause of mortality. The inability of anticancer agents to cross the blood-brain-barrier represents a critical challenge for successful treatment. We demonstrate that penfluridol administration to an orthotopic model of breast cancer suppressed tumor growth by 49%. On the other hand, penfluridol treatment inhibited the growth of metastatic brain tumors introduced by intracardiac or intracranial injection of breast cancer cells by 90% and 72%, respectively. Penfluridol-treated tumors from all three models exhibited reduced integrin β4 and increased apoptosis. Moreover, chronic administration of penfluridol failed to elicit significant toxic or behavioral side effects in mice. Taken together, our results indicate that penfluridol effectively reduces the growth of primary TNBC tumors and especially metastatic growth in the brain by inhibiting integrin signaling, and prompt further preclinical investigation into repurposing penfluridol for the treatment of metastatic TNBC.
- Feb 25th 2016 Don’t kill cancer, learn to live with it, say scientists
Controlling cancer rather than killing it could be the best way to fight the disease, according to scientists. I do like this concept indeed. I read a few years ago about it in an a scientific paper and I found the idea very good. The idea would be to use low dose effective treatments so that you do not kill all the cells sensitive to that treatment but enough to maintain a certain size. In this way the treatment responding cells will remain majority and will not give to the resistant cells the chance to take over and proliferate. Nice approach, at least in theory.
What causes cancer to grow and metastasize is not well understood by scientists. Now researchers have found a surprising link between the death of tumor-support cells and an increased risk of cancer metastasis in mice.
This study argues that killing cancer-associated fibroblasts (CAFs) may lead to metastasis. This is totally against the common believe that when trying to kill cancer we need to focus on killing the surrounding fibroblasts that support the growth of cancer. As a result, they suggest “time-controlled knockouts”. To me, this makes sense but also makes things more complicated. In this case, I would make sure that when using a treatment option, I would use one that targets fibroblast and the tumor at the same time, such as 3BP or other metabolic treatments. At least don’t target the fibloblast unless using at the same time an effective therapy against the tumor.
Tumors kill off surrounding cells to make room to grow, according to new research. Although the study was carried out using fruit flies, its findings suggest that drugs to prevent, rather than encourage, cell death might be effective at fighting cancer — contrary to how many of the current chemotherapy drugs work.
This is an interesting concept and reminds me of a discussion around telomerase activators which can be seen as anti aging substances. Some suggested that telomerase activators should be avoided by cancer patients as they would increase the life not only of good cells but also of bad cells. However, if is to agree with the above concept, that we may actually see the telomerase activators not only as anti aging but also anti cancer elements. One of such element with (debated – Ref) telomerase activation capability is the well known Procaine which is also used as a treatment in German clinics and first time discovered an applied as anti aging element in Romania by dr. Aslan. In the 1950s Dr. Ana Aslan of Bucharest, Romania performed experiments on lab animals injecting 2% Procaine and found that rats and rabbits live around 30% longer if given procaine injections. She wrote a book titled GH3 and became famous treating famous people. (Ref) The Procain product is called Gerovital and is available in Romanian pharmacies withouth prescription, in the form of pills or i.m. injections.
- Eosinophils orchestrate cancer rejection by normalizing tumor vessels and enhancing infiltration of CD8+ T cells
Tumor-associated eosinophilia is frequently observed in cancer. However, despite numerous studies of patients with cancer and mouse models of cancer, it has remained uncertain if eosinophils contribute to tumor immunity or are mere bystander cells. Here we report that activated eosinophils were essential for tumor rejection in the presence of tumor-specific CD8+ T cells. Tumor-homing eosinophils secreted chemoattractants that guided T cells into the tumor, which resulted in tumor eradication and survival. Activated eosinophils initiated substantial changes in the tumor microenvironment, including macrophage polarization and normalization of the tumor vasculature, which are known to promote tumor rejection. Thus, our study presents a new concept for eosinophils in cancer that may lead to novel therapeutic strategies.
- October 12th, 2015: Tamoxifen gives neutrophil a boost
Tamoxifen-treated neutrophils produced approximately three-fold more neutrophil extracellular traps (NETs), a mesh of DNA, antimicrobial peptides, enzymes and other proteins that neutrophils spew out to ensnare and kill pathogens.
- September 14th, 2015: How the ‘heat’ compound from chili peppers could help kill cancer cells
Capsaicin binds to a cell’s surface and affects the membrane, which surrounds and protects the cell. At high doses causes the membranes to come apart.
- August 28, 2015: New mechanism in adrenal gland tumors
The researchers identified a particular signaling pathway as the cause of this effect on the cells. “The PI3K/mTOR pathway is activated by the BMP7 protein and conveys signals for the cells to divide as well as to migrate,” explains team leader Pellegata. In order to verify this mechanism and to test potential future treatments, the team used two molecules. One molecule inhibits the signal transmission of BMP7; the other blocks the PI3K/mTOR downstream signaling pathway.
The toxicity of pharmacologic ascorbate is mediated by the generation of H2O2 via the oxidation of ascorbate. Our results demonstrate the potential clinical utility of pharmacologic ascorbate as a radiosensitizer in the treatment of pancreatic cancer.
Increasing Oxygen at the tumor site will increase the tumor susceptibility to natural killer (NK) cell€“mediated killing. Therefore, all the strategies focused on increseasing Oxygen in the body, such as Hydrogen Peroxide, Ozone therapy, etc. will increase the effectiveness of natural killer (NK) cell.
Clomipramine is an FDA-approved antidepressant drug.
A receptor on the surface of immune cells–the A2A adenosine receptor–is responsible for preventing T cells from invading tumors and for “putting to sleep” those killer cells that do manage to enter into the tumors. Now scientists shown that inhaling 40 to 60 percent oxygen (air offers 21 percent oxygen) weakened tumor-protecting signaling through the A2A adenosine receptor and awakened T cells that had gained the ability to invade lung tumors. And this can be further improved by the natural antagonist of the A2A adenosine receptor, which happens to be the caffeine in your coffee.
Scientists from the University of Sheffield found that when a therapy is effective in killing cancer, human body can trigger a process where white blood cells start clustering around blood vessels. These cells — called M2 macrophages — repair tissue damage and build new blood vessels, a process that sometimes helps the tumour to grow again after treatment. Using a drug available at pharmacies called Plerixafor (other names: Mozobil, AMD 3100, JM 3100, SDZ SID 791) can inhibit the repair tissue damage and build new blood vessels.
In my opinion, this is a great tool to add next to any effective anti-cancer treatment such as Salinomycin. The only challenge here seems to be the price which is about 7000 euro for a 24mg injection of Plerixafor. On the other hand, the same quantity of Plerixafor from pharma chem suppliers such as Sigma Aldrich costs a few hundred euros and it can be easily prepared as injection since it is water soluble.