Alternative Cancer Treatment Resources

Cancer is a devastating disease that affects millions of people every year. While the traditional approach to cancer treatment is chemotherapy and radiation therapy, many patients are looking for alternative treatments. According to the National Cancer Institute, more than 1.5 million American adults are treated for cancer each year. While conventional treatments are often successful upfront, they can be harsh, damaging to the body and fail to address the genesis of the cancer allowing for the cancer to return.

That is why many cancer patients turn to alternative cancer treatment which is more gentle and involves a holistic approach to healing the body for the long term. So if you’re looking for an alternative to traditional cancer treatments, following is just some of the research on cancer treatments used at Sunridge Medical Clinic.

Autohemotherapy

Hu, B., Zheng, J., Liu, Q., Yang, Y., & Zhang, Y. (2018). The effect and safety of ozone autohemotherapy combined with pharmacological therapy in postherpetic neuralgia. Journal of pain research, 11, 1637–1643. https://doi.org/10.2147/JPR.S154154

Ozone autohemotherapy is reported as being mainly used for cancer therapy. Findings show that; 1) Medical ozone has a strong bactericidal effect, and specific concentration of medical ozone can inhibit the growth and reproduction of herpes virus and promote the phagocytosis of leukocytes for herpes virus; 2) medical ozone can increase the oxygen-carrying ability and erythrocyte rheology of red blood cells, increase the oxygen supply for tissues and cells, improve the microcirculation in damaged nerve and skin tissue, and promote the repair of local nerves and tissue; 3) medical ozone mixed with blood can produce hydrogen peroxide (H₂O₂), which can be as an important messenger, activate the body’s immune system, initiate a series of chemical reactions, induce the production of interleukin and interferon and other cytokines to activate and regulate the immune system function, and, finally, restore the normal functioning of the thalamus for the pain loop; 4) ozone autohemotherapy can bring a pleasant sensation to the person, relieve the patient’s fatigue and depression, and improve physical strength and mental stability. In addition, reactive oxygen species (ROS) and lipid oxidative products (LOPs), believed to be involved in the biological progress of ozone, are produced immediately after ozone is dissolved in biological water (plasma, lymph, urine, interstitial fluid, etc.). ROS and LOPs have been reported to activate nuclear transcriptional factors, such as nuclear factor-erythroid 2–related factor 2, so as to alleviate pain. Finally, one study also speculated that ozone directly or indirectly acted on transmembrane proteins, intracellular cascades, and nuclear transcriptions to alleviate pain. In conclusion, the findings of this study demonstrated that ozone autohemotherapy combined with pharmacological therapy was superior to isolated pharmacological therapy.

Biological Detoxification

Mirna Jovanović, Ana Podolski-Renić, Mikhail Krasavin, Milica Pešić; The Role of the Thioredoxin Detoxification System in Cancer Progression and Resistance; Frontiers in Molecular Biosciences, May 2022; 10.3389/fmolb.2022.883297

It is a well-known fact that antioxidant detoxifying systems are of fundamental significance for cancer cell survival upon exposure to an anti-cancer drug. Therefore, the simultaneous shutdown of these defense systems can provide therapy success, lower systemic toxicity, and influence the patient’s life quality (Benhar et al., 2016; Yan et al., 2019). The thioredoxin (Trx) system is one of the vital threads in the cell’s antioxidant detoxification network, responsible for the preservation of redox homeostasis.

Classical Homeopathy

Milazzo, Stefania, Nancy Russell, and Edzard Ernst. “Efficacy of Homeopathic Therapy in Cancer Treatment.” European Journal of Cancer 42, no. 3 (2006): 282–89. doi:10.1016/J.EJCA.2005.09.025.

Five out of six trials included in this systematic review yielded positive results, which suggest the effectiveness of homeopathic remedies for cancer care. Cancer patients appear to have benefited from homeopathic interventions specifically for chemotherapy-induced stomatitis, radiodermatitis and general adverse events from radiotherapy. Breast cancer survivors, suffering from menopausal symptoms, experienced a general improvement on their quality of life.

Diagnostic Testing / Screening

Mallett S, Deeks J J, Halligan S, Hopewell S, Cornelius V, Altman D G et al Systematic Reviews of diagnostic tests in cancer: review of methods and reporting British Medical Journal BMJ 2006; 333:413 BMJ 2006; 333 :413 doi:10.1136/bmj.38895.467130.55

Diagnostic accuracy is essential for good therapeutic treatment. The case for systematic reviews is now well established, enabling efficient integration of current information and providing a basis for rational decision making.

Transparent reporting of review methods and detailed reporting of the clinical and methodological characteristics of the included studies and their results are important to enable a reader to judge the reliability of both the review and the individual studies and to assess their relevance to clinical practice and the meaning of the results reported in the review.

A lack of awareness of the complexities within diagnostic studies may have led to under-reporting of critical detail of review methods and included study characteristics. Test methods and materials often vary between studies for both reference and index tests, but many reviews do not give details for each study.

Heavy Metal Detoxification

Review Article Front. Pharmacol., 13 April 2021 Sec. Predictive Toxicology; Toxic Mechanisms of Five Heavy Metals: Mercury, Lead, Chromium, Cadmium, and Arsenic. https://doi.org/10.3389/fphar.2021.643972

The industrial activities of the last century have caused massive increases in human exposure to heavy metals. Mercury, lead, chromium, cadmium, and arsenic have been the most common heavy metals that induced human poisonings. Here, we reviewed the mechanistic action of these heavy metals according to the available animal and human studies. Acute or chronic poisonings may occur following exposure through water, air, and food. Bioaccumulation of these heavy metals leads to a diversity of toxic effects on a variety of body tissues and organs.

Heavy metals disrupt cellular events including growth, proliferation, differentiation, damage-repairing processes, and apoptosis. Comparison of the mechanisms of action reveals similar pathways for these metals to induce toxicity including ROS generation, weakening of the antioxidant defense, enzyme inactivation, and oxidative stress. On the other hand, some of them have selective binding to specific macromolecules. The interaction of lead with aminolevulinic acid dehydratase and ferrochelatase is within this context.

Reactions of other heavy metals with certain proteins were discussed as well. Some toxic metals including chromium, cadmium, and arsenic cause genomic instability. Defects in DNA repair following the induction of oxidative stress and DNA damage by the three metals have been considered as the cause of their carcinogenicity. Even with the current knowledge of hazards of heavy metals, the incidence of poisoning remains considerable and requires preventive and effective treatment. The application of chelation therapy for the management of metal poisoning could be another aspect of heavy metals to be reviewed in the future.

High-Dose Vitamin C Therapy and Cancer

Ngo B, Van Riper JM, Cantley LC, Yun J. Targeting cancer vulnerabilities with high-dose vitamin C. Nat Rev Cancer. 2019 May;19(5):271-282. doi: 10.1038/s41568-019-0135-7. PMID: 30967651; PMCID: PMC6526932.

Over the past century, the notion that vitamin C can be used to treat cancer has generated much controversy. However, new knowledge regarding the pharmacokinetic properties of vitamin C and recent high-profile preclinical studies have revived interest in the utilization of high-dose vitamin C for cancer treatment. Studies have shown that pharmacological vitamin C targets many of the mechanisms that cancer cells utilize for their survival and growth. In this Opinion article, we discuss how vitamin C can target three vulnerabilities many cancer cells share: redox imbalance, epigenetic reprogramming and oxygen-sensing regulation. Although the mechanisms and predictive biomarkers that we discuss need to be validated in well-controlled clinical trials, these new discoveries regarding the anticancer properties of vitamin C are promising to help identify patient populations that may benefit the most from high-dose vitamin C therapy, developing effective combination strategies and improving the overall design of future vitamin C clinical trials for various types of cancer.

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Intravenous Therapies

Alpha Lipoic Acid

Werida, R.H., Elshafiey, R.A., Ghoneim, A. et al. Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients. Support Care Cancer 30, 7281–7292 (2022). https://doi.org/10.1007/s00520-022-07124-0

Paclitaxel and doxorubicin are associated with neurotoxicity and cardiotoxicity respectively. This study aimed at investigating the role of alpha-lipoic acid (ALA) in counteracting paclitaxel-induced neuropathy and doxorubicin-associated cardiotoxicity in women with breast cancer.

This randomized double-blind placebo-controlled prospective study included 64 patients with breast cancer who were randomized into control group (n = 32) which received 4 cycles of doxorubicin plus cyclophosphamide (every 21 days) followed by weekly doses of paclitaxel for 12 weeks plus placebo tablets once daily and ALA group (n = 32) which received the same chemotherapeutic regimen plus ALA 600 once daily for 6 months.

Patients were assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE version 4.0) for grading of neuropathy and by 12-item neurotoxicity questionnaire (Ntx-12). The assessment included also echocardiography and evaluation of serum levels of brain natriuretic peptide (BNP), tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and neurotensin (NT). Data were analyzed by paired and unpaired t-test, Mann–Whitney U test, and chi-square test.

As compared to placebo, ALA provoked significant improvement in NCI-CTCAE neuropathy grading and Ntx-12 score after the end of 9^th and 12^th weeks of paclitaxel intake (p = 0.039, p = 0.039, p = 0.03, p = 0.004, respectively). At the end of the chemotherapy cycles, ALA resulted in significant decline in serum levels of BNP, TNF-α, MDA, and neurotensin (p < 0.05) as compared to baseline data and placebo.

Alpha-lipoic acid may represent a promising adjuvant therapy to attenuate paclitaxel-associated neuropathy and doxorubicin-induced cardiotoxicity in women with breast cancer.

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Artemisinin and Cancer

Thomas Efferth, From ancient herb to modern drug: Artemisia annua and artemisinin for cancer therapy, Seminars in Cancer Biology, Volume 46, 2017, Pages 65-83, ISSN 1044-579X, https://doi.org/10.1016/j.semcancer.2017.02.009. https://www.sciencedirect.com/science/article/pii/S1044579X17300299)

Artemisia annua L. is used throughout Asia and Africa as tea and press juice to treat malaria and related symptoms (fever, chills). Its active ingredient, artemisinin (ARS), has been developed as antimalarial drug and is used worldwide. Interestingly, the bioactivity is not restricted to malaria treatment. We and others found that ARS-type drugs also reveal anticancer in vitro and in vivo. In this review, we give a systematic overview of the literature published over the past two decades until the end of 2016. Like other natural products, ARS acts in a multi-specific manner against tumors. The cellular response of ARS and its derivatives (dihydroartemisinin, artesunate, artemether, arteether) towards cancer cells include oxidative stress response by reactive oxygen species and nitric oxide, DNA damage and repair (base excision repair, homologous recombination, non-homologous end-joining), various cell death modes (apoptosis, autophagy, ferroptosis, necrosis, necroptosis, oncosis), inhibition of angiogenesis and tumor-related signal transduction pathways (e.g. Wnt/β-catenin pathway, AMPK pathway, metastatic pathways, and others) and signal transducers (NF-κB, MYC/MAX, AP-1, CREBP, mTOR etc). ARS-type drugs are at the stairways to the clinics. Several published case reports and pilot phase I/II trials indicate clinical anticancer activity of these compounds. Because of unexpected cases of hepatotoxicity, combinations of ARS-type drugs with complementary and alternative medicines are not recommended, until controlled clinical trials will prove the safety of non-approved combination treatments.

Keywords: Artemisia annua; Artemisinin; Cancer; Chemotherapy; Drug repurposing; Qinhaosu; Malaria; Phytotherapy

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Careseng and Cancer

Jia, H. Yan, X. Bu, G. Liu; AntiCancer Pharmacology Of Careseng, A Natural Product Of Ginseng; Proc Am Soc Clin Oncol 22: page 888, 2003 (abstr 3571); University of British Columbia, Vancouver, BC, Canada.

For thousands of years ginseng (Panax Quinquefolium L.) preparations have been used for health remedies. The main ingredients in ginseng with therapeutic activity are Ginseng saponins (ginsenosides) but only few of these ginsenosides, notably Rh1/2 and Rg3, demonstrate cytotoxicity on cancer cells. Since most ginseng preparations contain only trace amounts of these anticancer compounds, effects of direct inhibition on cancer cell growth are limited with regular ginseng extracts.

In the present study, a specially formulated ginseng product, Careseng containing over 80% of Rh2 and Rh2-like ginsenosides, was tested on cultured breast, prostate, lung, pancreatic and brain cancer cell lines and in an intracranial glioma rat model to study anticancer properties.

Our results showed that in vitro, Careseng induced G1 arrest and differentiation at low concentrations (<20ig/ml) and caused apoptosis at higher concentrations (>40ig/ml) in all cancer cell lines tested. Careseng induced apoptosis was independent of P53, but requisite of caspase activation, as DEVD, a caspase blocker completely abolished this activity. In all cancer cell lines, Careseng?apoptotic index was dose dependent.

Furthermore, when Careseng was combined with Taxol, Mitoxantrone and Cisplatin in vitro, a synergistic effect on cytotoxicity was demonstrated. In a 9L glioma rat model, oral administration of Careseng?(25-50mg/kg) reduced mortality by 60%, and elongated the average life span of tumor bearing animals compared to controls (32+3 days versus 18+1 days; p<0.001). Acute (4000mg/kg) and chronic (300mg/kg/day for 8 weeks) toxicity tests in mice showed no significant adverse effects.

The above results demonstrate that Careseng has provocative and novel anticancer properties that render it an important new anticancer drug candidate which should be tested further in clinical studies.

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Cesium Chloride and Cancer

Sartori HE. Cesium therapy in cancer patients. Pharmacol Biochem Behav. 1984;21 Suppl 1:11-3. doi: 10.1016/0091-3057(84)90154-0. PMID: 6522427.

The effect of cesium therapy on various cancers is reported. A total of 50 patients were treated over a 3 year period with CsCl. The majority of the patients have been unresponsive to previous maximal modalities of cancer treatment and were considered terminal cases. The Cs-treatment consisted of CsCl in addition to some vitamins, minerals, chelating agents and salts of selenium, potassium and magnesium. In addition, a special diet was also instituted. There was an impressive 50% recovery of various cancers, i.e., cancer of unknown primary, breast, colon, prostate, pancreas, lung, liver, lymphoma, ewing sarcoma of the pelvis and adeno-cancer of the gallbladder, by the Cs-therapy employed.

There was a 26% and 24% death within the initial 2 weeks and 12 months of treatment, respectively. A consistent finding in these patients was the disappearance of pain within the initial 3 days of Cs-treatment. The small number of autopsies made showed the absence of cancer cells in most cases and the clinical impression indicates a remarkably successful outcome of treatment.

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Curcumin and Cancer

Giordano A, Tommonaro G. Curcumin and Cancer. Nutrients. 2019 Oct 5;11(10):2376. doi: 10.3390/nu11102376. PMID: 31590362; PMCID: PMC6835707. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835707/

Curcumin, a polyphenol extracted from Curcuma longa in 1815, has gained attention from scientists worldwide for its biological activities (e.g., antioxidant, anti-inflammatory, antimicrobial, antiviral), among which its anticancer potential has been the most described and still remains under investigation. The present review focuses on the cell signaling pathways involved in cancer development and proliferation, and which are targeted by curcumin. Curcumin has been reported to modulate growth factors, enzymes, transcription factors, kinase, inflammatory cytokines, and proapoptotic (by upregulation) and antiapoptotic (by downregulation) proteins. This polyphenol compound, alone or combined with other agents, could represent an effective drug for cancer therapy.

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DCA and Cancer

Tataranni T, Piccoli C. Dichloroacetate (DCA) and Cancer: An Overview towards Clinical Applications. Oxid Med Cell Longev. 2019 Nov 14;2019:8201079. doi: 10.1155/2019/8201079. PMID: 31827705; PMCID: PMC6885244. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6885244/

An extensive body of literature describes anticancer property of dichloroacetate (DCA), but its effective clinical administration in cancer therapy is still limited to clinical trials. The occurrence of side effects such as neurotoxicity as well as the suspicion of DCA carcinogenicity still restricts the clinical use of DCA. However, in the last years, the number of reports supporting DCA employment against cancer increased also because of the great interest in targeting metabolism of tumor cells. Dissecting DCA mechanism of action helped to understand the bases of its selective efficacy against cancer cells.

A successful coadministration of DCA with conventional chemotherapy, radiotherapy, other drugs, or natural compounds has been tested in several cancer models. New drug delivery systems and multiaction compounds containing DCA and other drugs seem to ameliorate bioavailability and appear more efficient thanks to a synergistic action of multiple agents. The spread of reports supporting the efficiency of DCA in cancer therapy has prompted additional studies that let to find other potential molecular targets of DCA. Interestingly, DCA could significantly affect cancer stem cell fraction and contribute to cancer eradication. Collectively, these findings provide a strong rationale towards novel clinical translational studies of DCA in cancer therapy.

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Germanium and Cancer

Cho JM, Chae J, Jeong SR, Moon MJ, Shin DY, Lee JH. Immune activation of Bio-Germanium in a randomized, double-blind, placebo-controlled clinical trial with 130 human subjects: Therapeutic opportunities from new insights. PLoS One. 2020 Oct 19;15(10):e0240358. doi: 10.1371/journal.pone.0240358. PMID: 33075061; PMCID: PMC7572073. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572073/

Germanium has long been considered a therapeutic agent with anticancer, antitumor, antiaging, antiviral and anti-inflammatory effects. Numerous clinical studies have explored the promising therapeutic effects of organic germanium on cancer, arthritis and senile osteoporosis. The immune activation property of organic germanium is considered the foundation of its various therapeutic effects. However, previous human clinical studies investigating immune activation with organic germanium compounds have certain limitations, as some studies did not strictly follow a randomized, double-blind, placebo-controlled design.

To build a more clinically substantiated foundation for the mechanism underlying its immunostimulation, we structured by far the most rigorous clinical study to-date with a group of 130 human subjects to examine changes in immune profiles following germanium supplementation. We used Bio-Germanium, an organic germanium compound naturally synthesized via a yeast fermentation process. An 8-week randomized, double-blind, placebo-controlled study was conducted with 130 subjects with leukocyte counts of 4–8 (×10³/μL) divided into the Bio-Germanium group and the placebo group. Anthropometric measurements; blood collection; biochemical analysis; urinalysis; and natural killer cell activity, cytokine and immunoglobulin assays were conducted.

Results showed the Bio-Germanium group exhibited NK cell activity increases at effector cell: target cell (E:T) ratios of 50:1, 10:1, 5:1 and 2.5:1 (12.60±32.91%, 10.19±23.88%, 9.28±16.49% and 7.27±15.28%, respectively), but the placebo group showed decreases (P<0.01). The difference in the IgG1 change from baseline to follow-up between the Bio-Germanium and placebo groups was significant (P = 0.044). Our results and earlier clinical study of Bio-Germanium confirm that Bio-Germanium acts as an effective immunostimulant by increasing the cytotoxicity of NK cells and activating immunoglobulin, B cells and tumor necrosis factor (TNF)-α (P<0.05). As we have added newly discovered clinical findings for germanium’s immunostimulation mechanism, we believe Bio-Germanium is a highly promising therapeutic agent and should certainly be further explored for potential development opportunities in immunotherapy.

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Glandular Therapy and Cancer

Li F, Fountzilas C, Puzanov I, Attwood KM, Morrison C, Ling X. Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy. Am J Cancer Res. 2021 Oct 15;11(10):5190-5213. PMID: 34765320; PMCID: PMC8569338. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8569338/

DDX5 (p68) is a well-known multifunctional DEAD-box RNA helicase and a transcription cofactor. Since its initial discovery more than three decades ago, DDX5 is gradually recognized as a potential biomarker and target for the treatment of various cancer types. Studies over the years significantly expanded our understanding of the functional diversity of DDX5 in various cancer types and extended our knowledge of its Mechanism of Action (MOA). This provides a rationale for the development of novel cancer therapeutics by using DDX5 as a biomarker and a therapeutic target. However, while most of the published studies have found DDX5 to be an oncogenic target and a cancer treatment-resistant biomarker, a few studies have reported that in certain scenarios, DDX5 may act as a tumor suppressor. After careful review of all the available relevant studies in the literature, we found that the multiple functions of DDX5 make it both a superior independent oncogenic biomarker and target for targeted cancer therapy. In this article, we will summarize the relevant studies on DDX5 in literature with a careful analysis and discussion of any inconsistencies encountered, and then provide our conclusions with respect to understanding the MOA of FL118, a novel small molecule. We hope that such a review will stimulate further discussion on this topic and assist in developing better strategies to treat cancer by using DDX5 as both an oncogenic biomarker and therapeutic target.

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Glutathione and Cancer

Kennedy L, Sandhu JK, Harper ME, Cuperlovic-Culf M. Role of Glutathione in Cancer: From Mechanisms to Therapies. Biomolecules. 2020 Oct 9;10(10):1429. doi: 10.3390/biom10101429. PMID: 33050144; PMCID: PMC7600400. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600400/

Glutathione (GSH) is the most abundant non-protein thiol present at millimolar concentrations in mammalian tissues. As an important intracellular antioxidant, it acts as a regulator of cellular redox state protecting cells from damage caused by lipid peroxides, reactive oxygen and nitrogen species, and xenobiotics. Recent studies have highlighted the importance of GSH in key signal transduction reactions as a controller of cell differentiation, proliferation, apoptosis, ferroptosis and immune function. Molecular changes in the GSH antioxidant system and disturbances in GSH homeostasis have been implicated in tumor initiation, progression, and treatment response.

Hence, GSH has both protective and pathogenic roles. Although in healthy cells it is crucial for the removal and detoxification of carcinogens, elevated GSH levels in tumor cells are associated with tumor progression and increased resistance to chemotherapeutic drugs.

Recently, several novel therapies have been developed to target the GSH antioxidant system in tumors as a means for increased response and decreased drug resistance. In this comprehensive review we explore mechanisms of GSH functionalities and different therapeutic approaches that either target GSH directly, indirectly or use GSH-based prodrugs. Consideration is also given to the computational methods used to describe GSH related processes for in silico testing of treatment effects.

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Immunotherapy and Cancer

Wang Y, Wang M, Wu HX, Xu RH. Advancing to the era of cancer immunotherapy. Cancer Commun (Lond). 2021 Sep;41(9):803-829. doi: 10.1002/cac2.12178. Epub 2021 Jun 24. PMID: 34165252; PMCID: PMC8441060. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600400/

Molecular changes in the GSH antioxidant system and disturbances in GSH homeostasis have been implicated in tumor initiation, progression, and treatment response. Hence, GSH has both protective and pathogenic roles. Although in healthy cells it is crucial for the removal and detoxification of carcinogens, elevated GSH levels in tumor cells are associated with tumor progression and increased resistance to chemotherapeutic drugs.

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IPT-Insulin Potentiation Therapy and Cancer

Vishwamitra D, George SK, Shi P, Kaseb AO, Amin HM. Type I insulin-like growth factor receptor signaling in hematological malignancies. Oncotarget. 2017 Jan 3;8(1):1814-1844. doi: 10.18632/oncotarget.12123. PMID: 27661006; PMCID: PMC5352101. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5352101/

The insulin-like growth factor (IGF) signaling system plays key roles in the establishment and progression of different types of cancer. In agreement with this idea, substantial evidence has shown that the type I IGF receptor (IGF-IR) and its primary ligand IGF-I are important for maintaining the survival of malignant cells of hematopoietic origin. In this review, we discuss current understanding of the role of IGF-IR signaling in cancer with a focus on the hematological neoplasms. We also address the emergence of IGF-IR as a potential therapeutic target for the treatment of different types of cancer including plasma cell myeloma, leukemia, and lymphoma.

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Mistletoe Extract and Cancer

Szurpnicka A, Kowalczuk A, Szterk A. Biological activity of mistletoe: in vitro and in vivo studies and mechanisms of action. Arch Pharm Res. 2020 Jun;43(6):593-629. doi: 10.1007/s12272-020-01247-w. Epub 2020 Jul 3. PMID: 32621089; PMCID: PMC7340679. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7340679/?report=classic

Mistletoe has been used as treatment of many diseases in traditional and folk medicine. To date, anticancer, immunomodulatory, cardiac, antidiabetic, hepatoprotective, neuropharmacological, antibacterial and antifungal properties of mistletoe extracts have been studied the most. In this review, we summarized in vitro and in vivo studies on the pharmacological activity of Viscum species. Furthermore, we proposed the possible mechanisms of action of this herb, which might include many signalling pathways.

Mistletoe could regulate either similar or different targets in various pathways that act on membrane receptors, enzymes, ion channels, transporter proteins and transcriptional targets. Still, pharmacological activities of mistletoe have been investigated mainly for crude extracts. It is a new field for scientists to determined which chemical compounds are responsible for the individual biological activities of mistletoe and how these activities are achieved. As a result, mistletoe might become a source of new complementary therapies supporting the treatment of many diseases.

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Oxidative Medicine Therapies and Cancer

Oxygen-free radicals, reactive oxygen species (ROS) or reactive nitrogen species (RNS), are known by their “double-sided” nature in biological systems. The beneficial effects of ROS involve physiological roles as weapons in the arsenal of the immune system (destroying bacteria within phagocytic cells) and role in programmed cell death (apoptosis). On the other hand, the redox imbalance in favor of the prooxidants results in an overproduction of the ROS/RNS leading to oxidative stress.

This imbalance can, therefore, be related to oncogenic stimulation. High levels of ROS disrupt cellular processes by nonspecifically attacking proteins, lipids, and DNA. It appears that DNA damage is the key player in cancer initiation and the formation of 8-OH-G, a potential biomarker for carcinogenesis. The harmful effect of ROS is neutralized by an antioxidant protection treatment as they convert ROS into less reactive species.

However, contradictory epidemiological results show that supplementation above physiological doses recommended for antioxidants and taken over a long period can lead to harmful effects and even increase the risk of cancer. Thus, we are describing here some of the latest updates on the involvement of oxidative stress in cancer pathology and a double view on the role of the antioxidants in this context and how this could be relevant in the management and pathology of cancer.

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Poly MVA and Cancer

Veena RK, Ajith TA, Janardhanan KK, Antonawich F. Antitumor Effects of Palladium-α-Lipoic Acid Complex Formulation as an Adjunct in Radiotherapy. J Environ Pathol Toxicol Oncol. 2016;35(4):333-342. doi: 10.1615/JEnvironPatholToxicolOncol.2016016640. PMID: 27992313. https://pubmed.ncbi.nlm.nih.gov/27992313/

Several investigations have been initiated to enhance the antitumor effect of radiation and ameliorate its adverse effects such as reducing blood cell counts and causing DNA damage in normal cells. Compounds that enhance the antitumor activity of radiation without reducing blood cell counts or damaging DNA in normal cells can be of immense use as an adjunct in radiotherapy. We evaluated the antitumor effect of a specific set of minerals, vitamins, and amino acids (Poly-MVA) (2 mL/kg, per os), with and without radiation, against Dalton’s lymphoma ascites (DLA) and Ehrlich’s ascites carcinoma (EAC) cell lines that were transplanted in a solid-tumor model. Whole-body γ-radiation exposure (2 Gy) was performed using 60Co.

Poly-MVA enhanced the antitumor effect of radiation when administered beforehand. Furthermore, Poly-MVA administered once daily for 2 wk, immediately after 4 Gy irradiation, protected DNA damage in peripheral blood. It also rendered protection against the radiation-induced reduction of platelet count.

The unique electronic and redox properties of palladium-α-lipoic acid complex in Poly-MVA appear to be responsible for the exhibited effect. The results conclude that the antitumor-enhancing and normal cell-protective effect of Poly-MVA warrants additional studies for its potential clinical application.

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Resveratrol and Cancer

Almatroodi SA, A Alsahli M, S M Aljohani A, Alhumaydhi FA, Babiker AY, Khan AA, Rahmani AH. Potential Therapeutic Targets of Resveratrol, a Plant Polyphenol, and Its Role in the Therapy of Various Types of Cancer. Molecules. 2022 Apr 21;27(9):2665. doi: 10.3390/molecules27092665. PMID: 35566016; PMCID: PMC9101422. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9101422/

Cancer is among the most prominent causes of mortality worldwide. Different cancer therapy modes employed, including chemotherapy and radiotherapy, have been reported to be significant in cancer management, but the side effects associated with these treatment strategies are still a health problem. Therefore, alternative anticancer drugs based on medicinal plants or their active compounds have been generating attention because of their less serious side effects. Medicinal plants are an excellent source of phytochemicals that have been recognized to have health-prompting effects through modulating cell signaling pathways. Resveratrol is a well-known polyphenolic molecule with antioxidant, anti-inflammatory, and health-prompting effects among which its anticancer role has been best defined.

Additionally, this polyphenol has confirmed its role in cancer management because it activates tumor suppressor genes, suppresses cell proliferation, induces apoptosis, inhibits angiogenesis, and modulates several other cell signaling molecules.

The anticancer potential of resveratrol is recognized in numerous in vivo and in vitro studies. Previous experimental data suggested that resveratrol may be valuable in cancer management or improve the efficacy of drugs when given with anticancer drugs. This review emphasizes the potential role of resveratrol as an anticancer drug by modulating numerous cells signaling pathways in different types of cancer.

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Vitamin C and Cancer

Magrì A, Germano G, Lorenzato A, Lamba S, Chilà R, Montone M, Amodio V, Ceruti T, Sassi F, Arena S, Abrignani S, D’Incalci M, Zucchetti M, Di Nicolantonio F, Bardelli A. High-dose vitamin C enhances cancer immunotherapy. Sci Transl Med. 2020 Feb 26;12(532):eaay8707. doi: 10.1126/scitranslmed.aay8707. PMID: 32102933. https://pubmed.ncbi.nlm.nih.gov/32102933/

Vitamin C (VitC) is known to directly impair cancer cell growth in preclinical models, but there is little clinical evidence on its antitumoral efficacy. In addition, whether and how VitC modulates anticancer immune responses is mostly unknown. Here, we show that a fully competent immune system is required to maximize the antiproliferative effect of VitC in breast, colorectal, melanoma, and pancreatic murine tumors. High-dose VitC modulates infiltration of the tumor microenvironment by cells of the immune system and delays cancer growth in a T cell-dependent manner. VitC not only enhances the cytotoxic activity of adoptively transferred CD8 T cells but also cooperates with immune checkpoint therapy (ICT) in several cancer types. Combination of VitC and ICT can be curative in models of mismatch repair-deficient tumors with high mutational burden. This work provides a rationale for clinical trials combining ICT with high doses of VitC.

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Nutritional Supplementation & Cancer

Nutritional supplements are widely used among patients with cancer who perceive them to be anticancer and antitoxicity agents. Large-scale, randomized cancer prevention trials have mainly been negative, with some notable adverse and beneficial effects. For example, these trials showed that beta-carotene increases the risk of lung and stomach cancer, vitamin E increases prostate cancer and colorectal adenoma, and selenium reduces gastric and lung cancer in populations with low selenium levels but increase rates in those with higher levels.

Both beta-carotene and vitamin E supplementation increase overall mortality. This article reviews phase II and III trials that examine the effects of multivitamins, antioxidants, vitamin D, and n-3 supplements on outcome and toxicity from cancer treatments. Although vitamin E and beta-carotene reduce toxicity from radiotherapy among patients with head and neck cancer, it has been found to increase recurrence, especially among smokers.

Antioxidants have mixed effects on chemotherapy toxicity, but there are no data on outcome. Vitamin D deficiency is relatively common among patients with cancer, and ongoing phase III trials are studying the effect of vitamin D on outcome as well as optimum vitamin D and calcium intakes for bone health. Docosahexanoic and eicosopentanoic acid supplements have mixed effects on cachexia and are currently being tested as potential adjuncts to maximize response to chemotherapy.

Harvie M. Nutritional supplements and cancer: potential benefits and proven harms. Am Soc Clin Oncol Educ Book. 2014:e478-86. doi: 10.14694/EdBook_AM.2014.34.e478. PMID: 24857143. https://pubmed.ncbi.nlm.nih.gov/24857143/

Nutritional supplementation tailored to an individual’s background diet, genetics, tumor histology, and treatments may yield benefits in subsets of patients. Clinicians should have an open dialogue with patients about nutritional supplements. Supplement advice needs to be individualized and come from a credible source, and it is best communicated by the physician.

Personalized Wellness Programs

Stoutenberg M, Sogor A, Arheart K, Cutrono SE, Kornfeld J. A Wellness Program for Cancer Survivors and Caregivers: Developing an Integrative Pilot Program with Exercise, Nutrition, and Complementary Medicine. J Cancer Educ. 2016 Mar;31(1):47-54. doi: 10.1007/s13187-014-0785-9. PMID: 25663357. https://pubmed.ncbi.nlm.nih.gov/25663357/

The Integrative Wellness Program (IWP) at the University of Miami Sylvester Comprehensive Cancer Center (SCCC) sought to provide integrative wellness education to cancer patients, survivors, and caregivers by offering instruction in exercise, nutrition, and complementary and alternative medicine. The objective of this study was to assess the impact of the IWP on the overall wellness of the individuals participating in the program. Three different 10-week versions of the IWP were conducted over a 1-year period. Each session focused on a different wellness topic presented through interactive lectures and applied activities.

A series of self-report questionnaires were administered at baseline and again at the completion of the program to assess improvements in physical activity levels, dietary habits, sleep hygiene, and quality of life. Participants were generally older, Caucasian, female, had higher levels of education, and still currently receiving treatment. Significant changes were observed in two measures: Starting the Conversation (-2.0 ± 2.40, p = .037) and the Sticking To It subscale of the Self-Efficacy and Eating Habits Survey (1.7 ± 1.22, p = .0013).

A trend for improvement in the Reducing Fat subscale of the Self-Efficacy Eating Habits (0.44 ± 0.60, p = .056) was also observed. Participant satisfaction surveys indicated high levels of satisfaction and applicability of the material presented. The significant improvements detected related to dietary habits, combined with the responses from the participant satisfaction surveys, suggest that the IWP was well received and can positively impact the overall wellness of cancer patients, survivors, and their caregivers.

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