Home » OutSmart Cancer

Tag: OutSmart Cancer

Cancer-SARS

Inflammation, Cancer and SARS-CoV2

Managing Inflammation and Inflammasome in both the Cancer Terrain and SARS-Cov2

There is a subset of cancer patients who suffer significantly more inflammation as well as the sequela of increased inflammation including ongoing cancer related fatigue, increased pain, cognitive deficits.   Similarly there is a subset of COVID-19 patients who suffer a cytokine storm and the wildfire of inflammation that leads to respiratory distress syndrome and mortality. Identifying patients with a higher risk of increased inflammation can be assessed by taking a thorough history in search of historical tendencies and patterns and an analysis of single nucleotide polymorphisms (SNPs).  Patients with IL1B, IL6 and NFkB  SNPs are more prone to developing greater inflammation in both syndromes.

inflammationThe inflammatory drivers and cytokines are similar in both cases: NFkB, TNFa, IL1, IL6, IL8, Inflammasone NLRP3, TGFb1, STAT3, JAK2, p38MAPK, Nrf2, AMPK

Activation of Inflammasome NLRP3 is correlated with the development of the SARS CoV2 cytokine storm.  Inflammasome activation is an important component of innate immunity which enhances inflammation.  Inflammasome activity is correlated with destructive inflammation particularly in viral diseases.  Inflammsome NLRP3  increases IL-1B is also  upregulated in the cancer terrain, particularly in metastatic lung cancer, breast cancer, fibrosarcoma and gastric carcinoma.

curcuminCurcumin exhibits anti-inflammatory and anti-inflammasome properties and can be used in both syndromes.  Curcumin impacts all of the above named inflammatory drivers along with inhibition of COX2 transcription.    Furthermore curcumin acts as an antioxidant increasing control of reactive oxygen species present with increased inflammation.

I recommend Designs for Health Curcumevail, Thorne Research Meriva and Euromedica Curapro.  In managing both the cancer terrain and the SARS CoV2 terrain the dose range is 2g-6g curcuminoids per day.

Another actor, Nrf2, is a nuclear transcription factor that increases the presence of antioxidant proteins when cells are stressed.   Management of the cancer terrain also includes support for normal function of Nrf2.  Nrf2 is highly expressed in the lungs and is responsible for inhibiting the activity of Inflammasome NLRP3.  Sulforaphanes include Di-indole methane, Indole-3-Carbinol and  Sulforaphane glucosinolate.  Broccoli, broccoli sprouts and kale are dietary sources of sulforaphanes.  

antioxidant

I recommend Designs for Health Broccoprotect and Thorne Research Crucera for a high quality source of sulforaphane glucosinolate 50mg twice daily.

Ultimately we may find that the core foundation and targeted supplements used in the OutSmart Cancer System for managing the cancer terrain ALSO protect our patients in the midst of a viral pandemic.

Selected References 

Rajendra Karki et al Inflammasomes and Cancer                                                                                                             PMID: 28093447 DOI: 10.1158/2326-6066.CIR-16-0269

Saeedi‐Boroujeni  et al COVID‐19: A Case for Inhibiting NLRP3 Inflammasome, Suppression of Inflammation with Curcumin?  Ali  https://doi.org/10.1111/bcpt.13503 Volume128, Issue1 January 2021 Pages 37-45

Howrylak JA, Nakahira K. 

Inflammasomes: Key Mediators of Lung Immunity. 

Annu Rev Physiol. 2017;79:471‐494. doi:10.1146/annurev-physiol-021115-105229

James W.Pinkertona1Richard Y.Kima1Avril A.B.RobertsonbJeremy A.HirotacLisa G.WoodaDarryl A.KnightaMatthew A.CooperbLuke A.J.O’NeilldJay C.Horvata1Philip M.Hansbroa  Inflammasomes in the Lung

Molecular Immunology Volume 86, June 2017, Pages 44-55         

Shih-Yi Chuang,1,2 Chih-Hung Lin,3,4 and Jia-You Fang

Natural Compounds and Aging: Between Autophagy and Inflammasome

Biomed Research Int. Volume 2014 |Article ID 297293 | 10 pages | https://doi.org/10.1155/2014/297293                                                    

József Tőzsér1 and Szilvia Benkő

Natural Compounds as Regulators of NLRP3 Inflammasome-Mediated IL-1β Production

Mediators of Inflammation Volume 2016 |Article ID 5460302 | 16 pages                                               https://doi.org/10.1155/2016/5460302

Rhodiola

Rhodiola, Mitochondria and Cancer Chemoprevention

Rhodiola (rosea and crenulata spp.) is a botanical adaptogen with broad application in cancer chemoprevention and mitochondrial support for cancer patients undergoing and recovering from cancer therapies.

Rhodiola is considered an adaptogen. It supports multiple functions that enhance resilience, responsiveness and recovery in the face of stress.

mitochondriaRhodiola came to widespread prominence when it was used by Olympic athletes, high altitude mountain climbers and long distance runners to enhance endurance and sustained energy over 50 years ago.

Rhodiola rosea and its primary active phytochemicals, salidroside and rosavins, have been widely studied for effects on cellular metabolism, energy production, inflammation control, oxidative stress, autophagy and cell death.

Salidroside is known to bind to the cell membrane and enter the cytosol via a membrane transporter where it influences AMPK and improves endothelial function and nitric oxide production, enhances glucose uptake and fatty acid oxidation and inhibit and gluconeogenesis and glycogen synthesis.

AMPK activity is required for cells to respond to stress and changes in energy balance.  It is primarily through this pathway that Rhodiola appears to enhance normal mitochondrial function and energy metabolism.  

Salidroside is water soluble and highly bioavailable via oral administration and its metabolites are excreted in the urine.

Rhodiola has also been shown to inhibit tumor promoting mTOR pathway and reduce angiogenesis and metastasis by down-regulating expression of HIF1a/HIF2a signaling. Reducint mTOR expression is a goal in chemoprevention and in optimizing the tumor microenvironment.

Rhodiola has demonstrated positive synergistic effects when combined with the chemotherapy agent cyclophosphamide.  

Rhodiola metabolites are excreted through the urine and one human study showed that patients with superficial bladder carcinoma who consumed Rhodiola orally reduced the average frequency of recurrence by 50%. 

Murine studies have shown that Rhodiola has Immuno-stimulating properties and increases, CD3 and CD4 T cells, Interferon-g and IL-2 cytokines.

Rhodiola demonstrates anti-inflammatory activity by inhibition of COX2, PLA2, NfkB, TNFa, IL-1B and IL-6 which are all upregulated in the tumor microenvironment. Additionally Rhodiola has inhibits expression of the NLRP3 inflammasome which is activated in the lung epithelia both during viral infections as well as malignancy.  (As a side note, this property of Rhodiola may also enhance vaccine adjuvant effect and maturation of dendritic cells and promote immune response to vaccine innoculation)

rhoRhodiola rosea and Rhodiola crenulata  are available as liquid botanical extract and in capsule form. Rhodiola extracts typically contain 3% salidrosides and 1% rosavins.  A therapeutic dose of Rhodiola is 3000mg/day.

A maintenance dose for cell protection and healthy aging ranges from 200-1000mg per day. Always use professional grade supplements and suppliers.

Rhodiola has a wide range of applications in chronic syndromes, healthy aging, and chemo-prevention and recovery by positively influencing multiple pathways in the cancer terrain and tumor microenvironment.

Selected References

Rhodiola and salidroside in the treatment

of metabolic disorders                                               
Xiang-Li Bai, et al, DOI : 10.2174/1389557519666190903115424

Rhodiola rosea L.: an herb with anti-stress, anti-aging, and immunostimulating properties for cancer chemoprevention

Yonghong Li , et al DOI: 10.1007/s40495-017-0106-1

mTOR, AMPK, and Sirt1: Key Players in Metabolic Stress Management                            
Silvia Cetrullo
, et al DOI: 10.1615/critreveukaryotgeneexpr.2015012975 

environmental-toxins

All Cancers Linked to Environmental Toxins

Making Environmental Health A Part of Health Care

Each month of the year is devoted to awareness of one or more cancers. September is devoted to multiple cancers.  

What do all of these cancers have in common?

There is an increasing volume of compelling evidence linking all types of cancer to environmental exposures.

Our knowledge of mechanisms linking exposures of toxicants to specific cancers is also increasing.  

environmental-pollution

There are two reasons that we as clinicians and care providers must be aware of the many contributing offenders and how to identify, assess, mitigate risk and safely remove body burden or toxicants in our patients.

Additionally, it is my practice to engage in patient education and patient teaching on the first or second visit to increase patient and family awareness about the importance of taking control of and reducing their toxic exposures as many toxicants are ubiquitous our homes, workplaces and communities.  Many toxicants include the use of common everyday products.    I also refer patients to these very reliable and up to date websites:  Environmental Working Group where foods, cleaning supplies, garden supplies are rated and their secondary site  Skin Deep Cosmetics Database for self-care and baby care products, including safe sunscreens.  They also have many downloadable publications for patients including 12 Hormone-Altering Chemicals and How to Avoid Them

Taking a good “ toxic exposures history” is important in all patients.  Of course, the very diagnostic methods and treatment modalities used in oncology are sources of toxic exposure as well!!  Many clinicians feel taking such a history from their patients will open us a Pandora’s box.

sewer-pollution

However, in the context of oncology, it is essential to do so, if only to bring awareness and to address the risk and health status not only of the patient, but also their family members.

My go to experts in this area include Dr. Walter Crinnion ND and Joseph Pizzorno, ND, both seasoned researchers and clinicians. They have recently published a well researched book  Clinical Environmental Medicine, which I consider required reading for all clinicians, especially those working with cancer patients.  There is a version for patients as well The Toxin Solution: How Hidden Poisons in the Air, Water, Food, and Products We Use Are Destroying Our Health--AND WHAT WE CAN DO TO FIX IT Dr. Crinnion’s has an excellent downloadable Toxic Exposure Questionnaire.  

The  American Academy of Environmental Medicine is an excellent resource for education and training and conferences where world-class experts convene.

Most in the patients control is their home environment and their food and water.

Fran Drescher’s Cancer Schmancer website has instructions for how to host a Detox Your Home Party.   

The first step is avoidance, avoidance, avoidance to reduce body burden, followed by appropriate supplements to help the body deal with what is there and finally safe and appropriate cleansing and detoxification interventions. Patients must also understand how to avoid re-exposure.

Resources:

Recommended Laboratories for Assessing Body Burden of Toxins 

(This is not a complete list and I have no financial relationship with any of these labs)

  • Great Plains Laboratory (heavy metals, environmental exposures, mycotoxins, glyphosate)
  • Genova Diagnostics (heavy metals, environmental chemicals)
  • RealTime Labs (Mold and Mycotoxins)
  • IMS Laboratory (Mold and Mycotoxins)
  • Quicksilver Scientific (Mercury)

*from a headline published in the New York Times

green-tea-extract

Green Tea Extract Reduces Severity of Radiation Dermatitis

The use of a solution containing a green tea extract has been shown to reduce both the incidence and severity of radiation-induced dermatitis in women undergoing adjunctive radiotherapy for breast cancer. This was the conclusion of a phase 2 randomized, placebo-controlled trial by a team of Chinese researchers.

Data from the World Health Organization indicates that in 2020, there were 2.3 million women diagnosed with breast cancer. In the treatment of women with breast cancer, radiation therapy is widely used conjunction with other therapies such as surgery, chemotherapy and hormonal therapies.  A common and frequent adverse effect of radiotherapy is radiation-induced dermatitis (RID) suffered by millions of women.

green-tea

The purpose of the current  study was to investigate the safety, tolerability and preliminary effectiveness of topical epigallocatechin-3-gallate (EGCG) for radiation dermatitis in patients with breast cancer receiving adjuvant radiotherapy.

A  solution of green tea extract  sprayed on the radiated areas of the skin reduced severity of radiation-induced dermatitis.

The Chinese team recruited women with breast cancer undergoing postoperative radiotherapy and randomized them (2:1) to receive either the green tea extract or placebo (normal saline solution).  These solutions were sprayed to the whole of the radiation field from the first day of therapy until two weeks after completion of treatment. 

A total of 165 women with a median age of 46 years were enrolled and randomized to EGCG, the primary catechin found in green tea or placebo.

The onset of radio-dermatitis was delayed by 2-3 weeks and the intensity and severity of the symptoms were significantly decreased in the treated group.  No skin toxicity was observed.

The authors concluded that prophylactic use of a green tea extract significantly reduced both the incidence and severity of RID and that it has the potential to become a new choice for skin care in women receiving radiotherapy.

Topical green tea extract supports restoration of skin integrity and control of inflammatory cytokines and oxidative stress in the skin. Green tea extract also reduces the acute skin-induced reactions including pain and sensations of burning, itching, pulling and tenderness.

Dr. Chilkov: Practical Application:

green-tea-leavesTopical Green Tea Extract Spray

To make a medicinal water extract: Place 8 organic green tea bags into a 16 oz glass jar or glass container.  Pour boiling water over the tea bags, cover immediately and steep for one hour.   After it has cooled to room temperature store covered in the refrigerator.  When ready to use transfer water extract to a a glass spray bottle.  Apply liberally to the radiation field before and after each radiotherapy session and three times daily for 3 weeks after the last radiotherapy session.  

Fresh Aloe Vera Gel poultice

Areas where skin is most impacted can be covered with. mashed fresh aloe vera gel and covered with a large gauze bandage.   This can easily be held in place underneath a sports bra or leotard or similar.  Apply fresh aloe gel twice daily. Allow to be in contact with the skin for several hours or overnight.  If you do not have access to a live aloe vera plant or fresh aloe gel you can use alcohol free aloe vera juice or aloe vera gel commonly found in natural foods stores.    Aloe Vera is the botanical of choice for repair of radiation damaged skin.

Topical Calendula Oil (not extract) is also a soothing topical anti-inflammatory agent for radiation induced dermatitis.  If the skin is very damaged, saturate a 4x4” gauze square and place over the affected area.

References:

Zhao H et al. 

Efficacy of Epigallocatechin-3-Gallate (EGCG)in Preventing Dermatitis in Patients With Breast Cancer Receiving Postoperative Radiotherapy: A Double-Blind, Placebo-Controlled, Phase 2 Randomized Clinical Trial JAMA Dermatol 2022

Zhao H, et al. 

Phase I study of topical epigallocatechin-3-gallate (EGCG) in patients with breast cancer

receiving adjuvant radiotherapy. Br J Radiol 2016; 89: 20150665.

Kyle T. Amber, BS et al

The Use of Antioxidants in Radiotherapy-Induced Skin Toxicity 

Integrative Cancer Therapies 2014, Vol. 13(1) 38–45

immunotherapy

Preventing Abdominal Radiation Enteritis and Promoting Quality of Life in Gynecological Cancer Patients

 

Insulin and fructo-oligosaccharide prevent acute radiation enteritis in patients with gynecological cancer and improve quality-of-life

Insulin

Background/objectives: The pathogenesis of enteritis after abdominal radiotherapy (RT) is unknown, although changes in fecal microbiota may be involved. Prebiotics stimulate the proliferation of Lactobacillus spp and Bifidobacterium spp, and this may have positive effects on the intestinal mucosa during abdominal RT.

Subjects/methods: We performed a randomized, double-blind, placebo-controlled trial involving patients with gynecological cancer who received abdominal RT after surgery. Patients were randomized to receive prebiotics or placebo. The prebiotic group received a mixture of fiber (50 inulin and 50% fructo-oligosaccharide), and the placebo group received 6 g of maltodextrin twice daily from 1 week before to 3 weeks after RT. The number of bowel movements and stool consistency was recorded daily. Diarrhea was evaluated according to the Common Toxicity Criteria of the National Cancer Institute. Stool consistency was assessed using the 7-point Bristol scale. Patients' quality-of-life was evaluated at baseline and at completion of RT using the EORTC-QLQ-C30 (European Organization for Research and Treatment of Cancer quality-of-life Questionnaire C30) test.

Results: Thirty-eight women with a mean age of 60.3±11.8 years participated in the study. Both groups (prebiotic (n=20) and placebo (n=18)) were comparable in their baseline characteristics. The number of bowel movements per month increased in both groups during RT. The number of bowel movements per day increased in both groups. The number of days with watery stool (Bristol score 7) was lower in the prebiotic group (3.3±4.4 to 2.2±1.6) than in the placebo group (P=0.08). With respect to quality-of-life, the symptoms with the highest score in the placebo group were insomnia at baseline and diarrhea toward the end of the treatment.

bowel movements

In the prebiotic group, insomnia was the symptom with the highest score at both assessments, although the differences were not statistically significant.

Conclusions: Prebiotics can improve the consistency of stools in gynecologic cancer patients on RT. This finding could have important implications in the quality-of-life of these patients during treatment.

stress-cancer

Does Stress Cause Cancer?

 

Lifestyle Factors That Impact Breast Cancer Risk

cancer-and-stress

  • Alcohol:  Drinking Alcohol Increases Risk of Breast Cancer
  • Weight and Body Composition: Excess body fat increases risk for post-menopausal breast cancer. Lean muscle, low body fat decreases risk of pre-menopausal breast cancers
  • Physical Activity: Sedentary behavior is linked to increased risk of breast cancer, while being active decreases the risk of breast cancer 

Vigorous activity decreases the risk for pre-menopausal breast cancer.

Moderate activity decreases risk for post-menopausal breast cancer.

Some evidence indicates that people who are physically active (both before and after diagnosis) have a greater chance of surviving breast cancer.

  • Breastfeeding: Reduces risk of both pre- and post-menopausal breast cancer
  • Sleep: Women who report sleeping less than 5 hours per night  before diagnosis have an increased risk of dying from breast cancer compared to women whose  pre-diagnosis sleep pattern was 7-8 hours per night.  Women who have disrupted circadian rhythms due to night shift work have an increased risk of breast cancer.

cancer-cells

Does Stress Cause Cancer?

Maladaptive and ongoing responses to stress mediated by the Autonomic Nervous System and Hypothalamic Pituitary Axis promote a tumor microenvironment that favors inflammation, oxidative stress, poor glycemic control, carcinogenesis, proliferation, angiogenesis and metastasis

Physiological Pathways, Bio-behavioural Processes and Oncogenesis:

  • Environmental and social processes activate interpretive processes in the central nervous system (CNS) that can subsequently trigger fight-or-flight stress responses in the autonomic nervous system (ANS) or defeat/withdrawal responses through the activation of the hypothalamic–pituitary–adrenal axis (HPA)
  • Individual differences in perception and evaluation of external events (coping) creates variability in individual ANS and HPA activity levels.
  • Over long periods of time, these neuroendocrine dynamics can alter various physiological processes involved in tumorigenesis, including oxidative metabolism, DNA repair, oncogene expression by viruses and somatic cells, and production of growth factors and other regulators of cell growth.
  • Once a tumour is initiated, neuroendocrine factors can also regulate the activity of proteases, angiogenic factors, chemokines and adhesion molecules involved in invasion, metastasis and other aspects of tumour progression.
  • CNS processes can also shape behavioural processes that govern cancer risk (for example, smoking, transmission of oncogenic viruses or exposure to genotoxic compounds).


Integrated Model of Bio-behavioral Influences on Cancer Pathogenesis Through Neuro-Endocrine Pathways

chart

In this model, bio-behavioural factors such as life stress, psychological processes and health behaviours (blue panel) influence tumour-related processes (green panel) through the neuroendocrine regulation of hormones, including adrenaline, noradrenaline and glucocorticoids (red panel). 

Central control of peripheral endocrine function also allows social, environmental and behavioural processes to interact with biological risk factors such as genetic background, carcinogens and viral infections to systemically modulate malignant potential (red panel). 

Direct pathways of influence include effects of catecholamines and glucocorticoids on tumour-cell expression of genes that control cell proliferation, invasion, angiogenesis, metastasis and immune evasion (green panel). 

Stress-responsive neuroendocrine mediators can also influence malignant potential indirectly through their effects on oncogenic viruses and the cellular immune system (red panel). 

These pleiotropic hormonal influences induce a mutually reinforcing system of cellular signals that collectively support the initiation and progression of malignant cell growth (green panel). 

Furthermore, neuroendocrine deregulation can influence the response to conventional therapies such as surgery, chemotherapy and immunotherapy (green panel). 

In addition to explaining bio-behavioural risk factors for cancer, this model suggests novel targets for pharmacological or behavioural intervention. 

(CTL, cytotoxic T lymphocytes; IL, interleukin; MRD, minimal residual disease; NKC, natural killer cell; TGFβ, transforming growth factor-β; TNFα, tumour-necrosis factor-α; TSH, thyroid-stimulating hormone.)

Dr. Nalini’s Adrenal Stress-Immune Support Protocol 

DAYTIME

Designs for Health Adrenotone   2/3x/day. With meals

All-in-one synergistic adrenal support formula. 

Metagenics Immucore 1/3x/day. With meals

Multidimensional Support for Healthy Immune Function

BEDTIME

Integrative Therapeutics  Cortisol Manager 2 caps one hour  before bedtime

  • Safe for use every night
  • Stress reducing sleep aid
  • Reduces cortisol levels for stress reduction and restful sleep.

https://us.fullscript.com/protocols/chilkov-dr-nalin-s-adrenal-stress-immune-support-kit

Treatment Plan should include 

Patient Teaching, Lifestyle and Dietary Guidelines and ongoing behavior change support

  • Dietary Guidelines -Nutrient Repletion-Glycemic Control
  • How to nurture parasympathetic tone
  • Sleep Hygeine
  • Self Regulation-Resilience- Stress and Mood Management guidelines
  • Monitoring Heart Rate Variability
  • Encourage Meditation-Tai Chi-Yoga-Deep Relaxation, Time in Nature
  • Acupuncture
  • Massage
  • Importance of Social Support
Using Phytochemicals

Using Phytochemicals Synergistically with Chemotherapy to Improve Efficacy and Outcomes

 

The role of polyphenols in overcoming drug resistance. 

In a paper published in January 2022, Maleki Dana et al, engage in a thorough review of multiple polyphenols which, when used concurrently with chemotherapy, can inhibit the development of chemo-resistance, rendering treatment more effective and for a longer duration of time.    

Most oncologists are wary of negative drug-herb, drug nutrient interactions. 

 

polyphenols-fruits

This review shows that we can use polyphenol phytochemicals synergistically with chemotherapy treatments to support efficacy and outcomes.

 

The Outsmart Cancer® System is an Integrative Cancer Care model seeking to develop highly individualized care plans that include the best therapeutic approaches and tools from multiple disciplines, combining a disease focused targeted pathology model with a whole biosystem health model to support the best outcomes for patients.

 

Acquired drug resistance has become a challenge that may result in treatment failure.  Multiple factors contribute to chemo-resistance in cancer cells. Acquired drug resistance occurs when cancer cells fail to respond to a previously effective treatment.  Intrinsic  chemo-resistance occurs when a pre-existing factor causes a drug to be inefficient or ineffective.

 

Due to the inherent heterogeneity of tumors, subpopulations of cells may develop resistance while other subpopulations remain sensitive to treatment.  

This is the rationale for using multiple agents which impact multiple signally pathways and receptors to target a wide array of heterogeneous cells.  This is also the rationale for using multiple nutriceuticals, botanicals and phytochemicals concurrently to address multiple signaling pathways and functions.

In this excellent review paper the author focuses on the multiple synergistic functions of polyphenols citing multiple studies.

 

Polyphenols from medicinal plants and food plants form a large part of our Materia Medica. Polyphenols include several subclasses such as catechins, flavonoids, flavones, flavonols, anthocyanins, isoflavones, curcuminoids, chalcones and phenolic acids. These natural compounds are widely found found in deeply pigmented fruits, vegetables, cocoa, seeds and green and black teas,

 

Not only do polyphenols inhibit multiple pathways and mechanisms of drug resistance, but also act to  confront many of the Hallmarks of Cancer, thus inhibiting and controlling the activity and viability of malignant cells.

 

The multiple functional roles of

  • Resveratrol
  • EGCG Epigallocatechin gallate
  • Curcumin 

are discussed and examined in depth examining multiple pathways, mechanisms of action and dosing.

Also discussed are additional well researched polyphenols, many of which are sourced from food plants as well as medicinal plants including

  • Quercetin 
  • Baicalin
  • Baicalien
  • Apigenin
  • Chrysin
  • Luteolin
  • Kaempferol

Mechanisms which lead to drug resistance in tumor cells

Malignant cells are highly adaptive and respond to toxic stressors such as chemotherapeutic drugs in the tumor micro-environment in service to their own survival.  Essential malignant cells are “smart” and they can not only co-opt normal physiologic and metabolic functions within cells to respond to the presence of toxic drug therapies.

  • Decreased Drug Uptake by tumor cells
  • Drug Efflux from tumor cells (membrane pumps)
  • Alterations in drug metabolism
  • Epigenetic Modification and Signaling
  • Inhibition of Programmed Cell death via apoptosis, autophagy and necrosis in tumor cells
  • Alterations in DNA repair 
  • Activity of Cancer Stem Cells
  • Redox Capacity of cells in response to oxidative stress
  • Alterations in Epithelial to Mesenchymal Transition, Invasion and Metastatic Progression

Not only are polyphenols capable of addressing the common Hallmarks of Cancer, but they can also inhibit the multiple ways that malignant cells seek to survive in the face of drug therapies.  

 

Therefore, we should strategically combine chemo-therapeutic  agents with selected polyphenols to both enhance therapeutic effect as well as inhibit the development of drug resistance. 

 

This leads to greater therapeutic benefit, increased duration of action as well as skillful management of adverse effects.

I encourage you to read this paper in detail for a deep and detailed review of the mechanisms of these pleomorphic multitaskers polyphenols.  The polyphenols mentioned in this paper have a history of wide use and safety.

 

Our role is to both eradicate and inhibit neoplastic cells as well as nurture and support the health of the patient.  This is at the heart of the OutSmart Cancer® System.

 

References

 

The Role of Polyphenols in Overcoming Cancer Drug Resistance: A Comprehensive Review 

Maleki Dana et al

Cellular and Molecular Biology Letters (2022) 27:1

https://doi.org/10.1186/s11658-021-00301-9

 

Hallmarks of Cancer: The Next Generation

Douglas Hanahan, Robert A. Weinberg, 2011

https://doi.org/10.1016/j.cell.2011.02.013

 

Revisiting the hallmarks of cancer

Fouad YA, Aanei C.. Am J Cancer Res. 2017 May 1;7(5):1016-1036. PMID: 28560055; PMCID: PMC5446472.

 

Probiotics

Oral Probiotics Reduce Complications of Surgery

 

Using probiotics before surgery prepares the patient for post operative stressors and complications. Using probiotics after surgery continues the support for the microbiome post operatively.

It is my practice to administer oral probiotics both before and after surgery with all of my patients.

Overall, using probiotics as part of pre-op and post-op care offers the following benefits

  • Reduction in Pro-Inflammatory Cytokines
  • Prevention of Surgical Infection and Sepsis 
  • Promotion of gastrointestinal microbial balance
  • Amelioration of adverse effects of oral antibiotics 
  • Decrease in adverse effects of opioids on gastrointestinal function
  • Promotion of Wound Healing at the surgical site

Use of oral probiotics is well tolerated and safe for use not only in cancer related surgeries but in a wide range of surgical procedures. 

Researchers conducting a randomized double blind placebo controlled study on the post operative effects of oral probiotics in patients undergoing resection for colorectal cancer concluded that probiotics not only decrease rates of infection at the incision site, respiratory and urinary systems but also inhibit proinflammatory factors such as TNFa, IL-17A , IL-17C, IL-22, IL-10 and IL-12.   Subjects in the treatment arm were given a 30 billion CFU mixture of six viable strains of Lactobacillus acidophilus, L. lactis, L. casei, Bifidobacterium longum, B. bifidum, and B. infantis twice daily for 6 months beginning 4 weeks postoperatively. [NB: I recommend starting pre-operatively].   Subjects in this arm did not experience infection, diarrhea or require antibiotics.

Zaharuddin L, Mokhtar NM, Muhammad Nawawi KN, Raja Ali RA. A randomized double-blind placebo-controlled trial of probiotics in post-surgical colorectal cancer. BMC Gastroenterol. 2019 Jul 24;19(1):131. doi: 10.1186/s12876-019-1047-4. PMID: 31340751; PMCID: PMC6657028.

In another study of patients receiving abdominal surgeries  oral probiotics were administered for 8 weeks.  The strains included were  L. plantarum, L. lactis, and L. delbrueckii. The study found statistically significant postoperative treatment reductions in abdominal pain and bloating, and significant improvements in stool formation. No clinically relevant adverse events were reported, and the treatment was well-tolerated by all patients. 

Bonavina L, Arini A, Ficano L, Iannuzziello D, Pasquale L, Aragona SE, Ciprandi G, On Digestive Disorders ISG. Post-surgical intestinal dysbiosis: use of an innovative mixture (Lactobacillus plantarum LP01, Lactobacillus lactis subspecies cremoris LLC02, Lactobacillus delbrueckii LDD01). Acta Biomed. 2019 Jul 10;90(7-S):18-23. doi: 10.23750/abm.v90i7-S.8651. PMID: 31292422; PMCID: PMC6776165.

In a recent 2021 Review of 14 studies of patients receiving gastrointestinal surgeries, a disruption of intestinal microbiome is identified and the prevalence of specific bacteria had significantly changed after surgery.

Ferrie S, Webster A, Wu B, Tan C, Carey S. Gastrointestinal surgery and the gut microbiome: a systematic literature review. Eur J Clin Nutr. 2021 Jan;75(1):12-25. doi: 10.1038/s41430-020-0681-9. Epub 2020 Jul 13. PMID: 32661352.

Another Review of 10 studies also identified post operative changes in the composition of the intestinal microbiome in patients receiving gastrointestinal surgeries  and posits that complications after gastrointestinal surgeries are linked to changes in the composition of the gut flora.

Lederer, A. K., Pisarski, P., Kousoulas, L., Fichtner-Feigl, S., Hess, C., & Huber, R. (2017). Postoperative changes of the microbiome: are surgical complications related to the gut flora? A systematic review. BMC surgery, 17(1), 125. https://doi.org/10.1186/s12893-017-0325-8

A study on the use of specific probiotics in patients undergoing resection for  colorectal cancer concluded that inflammatory cytokines and serum zonulin levels significantly decreased with probiotics. Probiotic ingestion resulted in compositional changes in gut microbiota; greater increases and decreases in healthy vs pathogenic bacteria, respectively, occurred with probiotics. Compositional increase in healthy bacteria was associated with reduced white blood cells, neutrophils, neutrophil-lymphocyte ratio, and zonulin. Bifidobacterium composition was negatively correlated with zonulin levels in the probiotic group, indicating repair of intestinal epithelium as an effective barrier. Probiotics improved postoperative flatus control and modified postoperative changes in microbiota and inflammatory markers.   In this study oral probiotics were administered both pre-op and post-op.  Probiotic supplementation included a mixture of three probiotic strains (Bifidobacterium animalis subsp. lactis HY8002 (1 × 108 cfu), Lactobacillus casei HY2782 (5 × 107 cfu), and Lactobacillus plantarum HY7712 (5 × 107 cfu)

Park, I. J., Lee, J. H., Kye, B. H., Oh, H. K., Cho, Y. B., Kim, Y. T., Kim, J. Y., Sung, N. Y., Kang, S. B., Seo, J. M., Sim, J. H., Lee, J. L., & Lee, I. K. (2020). Effects of PrObiotics on the Symptoms and Surgical ouTComes after Anterior REsection of Colon Cancer (POSTCARE): A Randomized, Double-Blind, Placebo-Controlled Trial. Journal of clinical medicine, 9(7), 2181. https://doi.org/10.3390/jcm9072181

Breast-Cancer

Changing the Management of Cancer with Personalized Testing

 

Personalized cDNA surveillance for patients with high-risk breast cancer

Is there a more sensitive technology that can detect preclinical breast cancer progression?

It is now possible to monitor fragments of cell free tumor DNA (ctDNA) circulating in the blood. This falls under the umbrella of “liquid biopsies” which monitor tumor burden, tumor response to treatment and early signs of recurrence or progression without a scan or need for a new surgical or biopsy tissue sample.

  • “Up to 30% of patients with breast cancer relapse after primary treatment.
  • There are no sensitive and reliable tests to monitor these patients and detect distant metastases before overt recurrence.
  • Breast cancer cell free tumor DNA blood test (liquid biopsy) can detect recurrence up to 2 years earlier than currently available conventional serum tumor markers and radiologic studies.
  • Cell free tumor DNA assays predict breast cancer recurrence earlier and with greater accuracy than traditional tools by using a highly-personalized molecular residual disease assay.

A cell free tumor DNA (ctDNA) assay is a personalized, tumor-informed assay with the power to give you earlier, clearer insight into your patient's disease. By detecting and quantifying ctDNA, you can optimize your ability to assess risk, predict recurrence, and monitor treatment response in those most at risk for progression.

This technology can be used to monitor a wide range of cancers. While this type of monitoring has not yet been widely adopted as “standard of care” I encourage you to educate all of your patients and their care providers to adopt the use of this highly reliable screening tool now.

Here, we demonstrate the use of personalized circulating tumor DNA (ctDNA) profiling for detection of recurrence in breast cancer.”

Cell free tumor DNA assays use a sample of the patient’s tumor tissue to develop a unique DNA fingerprint. After that, follow-up blood draws capture changes in the level of ctDNA, giving clinicians a better picture of a patient’s risk of recurrence without the need for another tissue sample and may decrease the need for frequent scans and repeated frequency of exposure to radiation and contrast material.

neodjuvant

A recent study “demonstrates that patient specific ctDNA analysis can be a sensitive and specific approach for disease surveillance for patients with breast cancer. More importantly, earlier detection of up to 2 years provides a possible window for therapeutic intervention. “(1)

Currently, there are no sensitive and specific clinical tests available to follow patients with breast cancer after primary treatment. Signatera developed a patient-specific method to analyze circulating tumor DNA (ctDNA) that allows for monitoring of these patients regardless of molecular genotype. In this study, we analyzed 208 blood samples from 49 patients monitored longitudinally for up to 4 years after completion of adjuvant chemotherapy to determine whether personalized ctDNA assays can allow for more effective monitoring than current clinical tests such as CA 15-3. Remarkably, for the patients that recurred, our test detected molecular relapse up to 2 years ahead of clinical relapse (median, 8.9 months) with 89% sensitivity and 100% specificity. This may provide a critical window of opportunity for additional therapeutic intervention.” (1)

 

hope

Data from a retrospective cohort analysis of EBLIS, a study designed to determine the lead interval between ctDNA detection and clinical metastatic disease, and to determine whether ctDNA in plasma can detect recurrent disease earlier than traditional methods, demonstrated that Signatera can accurately predicts metastatic relapse with a significant lead time over imaging and CA 15-3 (200 days on average)

Neoadjuvant

“…our study shows promise that early response prediction by highly sensitive ctDNA analysis in high-risk early breast cancer patients may facilitate a timely and judicious change in treatment to improve patients’ chances of achieving favorable long-term outcomes.(2)

Surveillance

Patients undergoing treatment as well as those who have completed their course of treatment can be assessed both for response to treatment during a course of therapy as well as for early signs of reurrence after treatment has been completed. In a study of patients undergoing treatment with Pembrolizumab, a checkpoint inhibitor.

“Baseline ctDNA concentration correlated with progression-free survival, overall survival, clinical response and clinical benefit. This association became stronger when considering ctDNA kinetics during treatment. All 12 patients with ctDNA clearance during treatment were alive with median 25 months follow up. This study demonstrates the potential for broad clinical utility of ctDNA-based surveillance in patients treated with ICB.” (3)

Recommended labs offering this technology include Natera, INVITAE, Foundation One, Caris Life Sciences. All of these labs are highly regarded in the oncology community. (Disclosure: I have no financial relationships with any of the labs recommended in this article.)

How often should these assays be performed?
I recommend monitoring monthly during active treatment to determine if the current treatment is effective and continuing to be effective. This is a way to identify treatment resistance early.

top10-badgeI recommend monitoring every three months during the first two years after completing treatment or for patients with advanced receiving ongoing treatments. (For example advanced breast cancer patients receiving hormonal treatments, immunotherapy treatments, checkpoint inhibitor treatments or chemotherapy treatments over long periods of time.)

For long term survivors I recommend monitoring every 6 months until the 10 year No Evidence of Disease anniversary.

This is the same schedule of monitoring that we use in the OUTSMART CANCER® System to follow measurable biomarkers in the tumor microenvironment.

Discover how you can join
Foundations of Integrative Oncology Professional Online Training
Master the OUTSMART CANCER® System
Receive Monthly Live Mentoring and Case Supervision
from Dr. Nalini Chilkov
CLICK HERE

Clinical Pearl-cancer

Clinical Pearl: Chemotherapy Reduces Magnesium to Dangerously Low Levels

 

Hypomagnesia occurs in 29-100% of cancer patients receiving chemotherapy.

Magnesium deficiency is common in cancer patients, especially those receiving chemotherapy.  Magnesium is the second most abundant intracellular cation after potassium. It is involved in >600 enzymatic reactions in the body.

Hypomagnesia induces  fatigue , mitochondropathy (compromised mitochondrial function )and risk for neuropathy, nephropathy as well as abnormal cardiovascular function (arrhythmia, hypertension) immune dysfunction, headache and altered bone and Vitamin D metabolism.  Hypomagnesia is associated with nausea, vomiting, headache, myalgia, constipation, anxiety, insomnia and depression, all common complaints of cancer patients.

Long term and extreme hypomagnesia promotes cancer treatment related fatigue, cortical blindness, insulin resistance, prolonged QT interval, hypertension, seizures, tremor, psychiatric disturbances, migraine headaches and is associated with chronic inflammation and oxidative stress.

Magnesium status declines with age.

As cancer patients are typically over 50 years old, hypomagnesia may be present long before diagnosis. Pre-menopausal women and athletes also have higher needs of magnesium and may be deficient. 

This may influence the tumor microenvironment towards carcinogenesis, tumorogenesis, proliferation and progression.

Both oral and intravenous repletion relieve many of the hypomagnesia related adverse effects.

Adverse effects can be prevented by supplementing with magnesium in advance of as well as after chemotherapy. In a health model, keep patients replete with Magnesium at times to optimize function, prevent deficiency syndromes and adverse symptoms of chemotherapy.

Monitoring and Management of Magnesium Status

All patient care plans include oral Magnesium Glycinate Chelate

Daily Dose: 600-900mg daily in capsule, liquid or powder form

(Glycinate and Bis-Glycinate chelates are more well absorbed and less likely to have a laxative effect than other forms of magnesium chelate). Excess oral magnesium can lead to diarrhea. Spread out oral dosing over 3-4 doses per day to achieve repletion without loose stool.

Extreme Hypomagnesia can be quickly repleted by intravenous infusion.

All patients are monitored for Serum RBC Magnesium to assess magnesium status every 3-6 months long-term and monthly during active chemotherapy.

Serum Magnesium is not a reliable indicator of Magnesium deficiency.

 

Dietary Sources of Magnesium include:

Almonds, cashews, brazil nuts, pumpkin seeds, flaxseeds, cocoa, avocados, dark leafy greens, seaweed

 

Chemotherapeutic agents that induce hypomagnesia:

Platinum Chemotherapy Agents : Oxaliplatin, Cisplatin, Carboplatin and

Taxanes:  paclitaxel (Taxol) nab-paclitaxel (Abraxane), docetaxel (Taxotere),Cabazitaxel (Jevtana).

Vinca alkaloids vinblastine, vincristine, vindesine, and vinorelbine.