CovidRxExchange – A year into the Journey

As I take this moment to recap our one year journey with CovidRxExchange, with all humility I wish to honor and pay our gratitude to our Patrons, Mentors and SPOCs, Executive and our various teams who helped evolve CovidRxExchange as an initiative to reckon with –

Patrons –

Dr. Vikas Mahatme, Ophthalmologist, Padmashree, and Rajya Sabha Member
Dr. Sunil Deshmukh, Radiologist and Former, Minister, Govt. of Maharashtra.
Wing Commander Babu, Formerly IAF
Mr. I. S. Chahal, Commissioner, Mumbai
Dr. Zodpey, VP, PHFI, Delhi,


We are deeply humbled and honored to have mentors like –
Prof. Emeritus Dr. Manbar Rawat, a Prof. of great respect and repute across multiple generations.
Prof. Emeritus Dr. Vilas Jahagirdhar, Formerly, Prof Microbiology and Dean
Prof. Uday Bodhankar, Formerly, IAP President, VP COMHAD, UK
Prof. Vrinda Sahasrabhojaney, Retd. Prof. Medicine.
Dr. Naveen Thacker, Director, IAP

Intent and Objective:

CovidRxExchange, a global nonprofit initiative, started in March 2020 to disseminate expertise, insight, and experience in managing Covid for the doctors, Health Care policymakers, and policy planners, and administrators. The intent is to enable doctors across borders to leverage the expertise they have honed in Covid patients’ care.

In March 2020 (exactly a year back), our initial foray was to disseminate knowledge and expertise from the US to the experts at Mumbai. We arranged our first call between Dr. Toraskar, Chief of Critical Care at Wockhardt and HOD of Cardiology at Nair Hospital, and two experts from the US, who had by then gained significant experience managing critical cases of Covid. From that experience, we realized, it is best to institutionalize the knowledge transfer and make it global. After that, we started panel discussions on the practical care of Covid in HDU and ICU.

Over a period of time, as Covid kept raging across countries, economies, globally, nationally, and regionally, we realized the needs got more specific, and we differentiated our nonprofit services to include more services under our gamut of CovidRxExchange.

Scope and Out of Scope: We are aggregators and disseminators of expertise, insight, and experience. We occasionally conduct our own research. We are a global organization.

Our Ethical Values

CovidRxExchange adheres to strict ethical guidelines. Nondiscrimination and noncommercial form the backbone of our services. We are an inclusive organization devoid of leaning towards any political ideology or any faith-based ideology. We are committed to translating academic evidence-based medicine to enable doctors, policymakers, and administrators. We are noncommercial and agnostic of vendor bais in providing our nonprofit services.

Activities and Accomplishments:

A. Our Initial Engagement – Panel Discussions and Second Consultations

After conducting several panel discussions, we were approached for several second consultations. Our next group was the second consult, and our global group of experts offered a second consult in several cases. Dr. Ajay Chaurasia (Cardiology, HOD, Nair Hospital), Dr. Nandita Divekar (UK), Dr. Rahul Sarkar (UK), Dr. Hettiarchi (UK) and Dr. Sandip Banerjee (UK),

B. Web-based Knowledge Repository (Lifecycle and Extended Lifecycle Approach)

Eventually, we created a web-based repository, a library with a Lifecycle approach to deal with Covid. Our lifecycle approach provides end-to-end case expertise of different aspects of covid from remote consult, first visit, admission (floor) to HDU, ICU, discharge, and bereavement.

As Long Haul disease became prevalent, we extended our Lifecycle Model to Extended Lifecycle Model, including Stress Management for Doctors and HCW and rehabilitation.

C. Risk Management: Extending Individual Care to Institutions, Cities, and Corporations.

Realizing that Covid was no more a patient condition, we created a 3×3 model. The 3×3 model extended the services to institutions, cities, and corporations. Thus the policy planners too came under the aegis of Covid Care. We helped the City of Coimbatore, An City (Anonymous) with significant Covid to identify and restructure their Covid, and did a post facto analysis for a metropolitan area for What best could have been done. Indore team (comprising of Dr. Nishant Khare, Dr. Sanjay Dhanuka, Dr. Anand Sanghi, and Dr. Gaurav Gupta), the UK Team (comprising of Dr. Divekar, Dr. Banerjee, Dr. Sarkar), the US Team (comprising of Dr. Lakshimi Sambathkumar, Dr. Arvind Virmani and I), and the Mumbai Team (comprising of Dr. Chaurasia, Dr. Ashok Anand, Dr. Hemant Bhandari, and Dr. Pankaj Maheshwari), worked along with the Coimbatore Commissioner, Deans, and Professors to provide a blueprint for Covid mitigation in the Corporation of Coimbatore. Dr. Rajamani and Ms. Kruthka Govindarajalu, Director, Smart City, Coimbatore, played a pivotal role.

D. Tribals and Areas of Deprived Resources: Eventually, as Covid made inroads into the tribal areas/interiors and understanding that 10% of India’s population lives in Tribal Areas, we developed our Tribal Covid Model. Dr. Ashish Satav, Dr. Sahasrabhojaney, Amod, and I, spearheaded this Tribal Covid Model. Realizing that the economically deprived areas and tribals areas have shared problems, we consolidated this capability under Tribal and Areas of Deprived Resources.

E. Holistic Health: Mindfulness, Sleep, Exercise, Nutrition, and Yoga, are crucial to achieving normal health. Ms. Gomathy Periatheruvadi, an Entrepreneur and Executive from the US, is leading this capability.

F. Rehabilitation and Long Haul: This is one area where we are still striving to expand our footprint. We are exploring to develop this capability, and Dr. Mariya Jiandani has shown interest and bandwidth to expand these services.

G. Vaccines – Developing a requisite immunity is based on critical success with Vaccine deployment. Vaccines emerged as a significant area that our doctors needed an incredible amount of support. Realizing this, we organized a series of panel discussions and one on one calls to address patient concerns.

H. Variants – Mutations and their aggregation into variants created a different challenge, both in transmission, infectivity, and the second/third/fourth surge across nations. We have set up a dedicated capability and integrated this under the vaccine capability. We are exploring the implications of the variants such as B1.1.7, B1.351, P.1, B1.521, and the recent variants found in India and other countries on the transmission, infectivity, morbidity, and mortality. Dr. Mukul Acharya (UK), Dr. Anand Kawade (India), Dr. Nitin Wairagkar (US), Dr. Kedar Toraskar (Mumbai), Dr. Naveen Thacker (India), Dr. Suhasini Balasubramiam (Chennai), Dr. Anita Mathew (Mumbai), Dr. Mala Kaneria (Mumbai), and Dr. Neetu Jain (Delhi) are working under the mentorship of Prof. Dr. Rawat and Prof. Jahagirdhar.

I. Dispelling Rumors: As rumors are flying rife; we are identifying SPOC’s to evaluate, analyze, and provide a scientific evidence-based rationale to dispel rumors

J. Socialization of scientific understanding into commonly understood language is important as we consider that if our nonmedical community is aware, they can be the necessary pivot to transgressing towards success. Thus dispelling ‘Rumors and Socialization’ are emerging as recent capabilities.

K. Liaison: Covid needs an adequate translation to policy and execution. We are currently working on establishing a capability to connect with the policymakers at different Govt. Machinery levels.

L. Awareness: Specifically for the nonmedical folks based in the US, we have created an Awareness Group to share information on awareness.

M. Strategy, Risk and Program: With my background in Strategy, Governance, and Risk Management made me realize that these should include these as independent capabilities. Thus, Strategy (Wing Commander Babu and I), Governance (Founders) and Risk (Amod and I) are maturing this capability. We reinvented the industry approach on Risk Management and tweaked it to align with Covid and Medical care. Concurrently, as capabilities were sprawling, we realized a common framework should encapsulate the entire initiative. Thus, we initiated program management (with a CMMI/ISO) capability to standardize for all the capabilities. Manish Singhal has taken the onus to develop this nascent capability.

N. Legal, Compliance, Finance: While some of these capabilities are a doctor (customer) facing, many capabilities are operational and happening on the backend: operations, Legal, Compliance, and Finance capabilities. Mr. Yogesh Vyas, Mr. Amod Manjrekar, and

O. Technology: Manish Singhal, Amod Manjrekar, Pankaj Bhakta, and Shriram Devata provide that support. This is still an incipient and nascent capability where we are expecting significant development.

P. CME: These capabilities are in embryonic stages. We are exploring global sponsors and accreditation for this capability.

Q. Editorial: We are upgrading our capability to provide updates (weekly, daily, and flash). Currently, we are scaling capability to include over 2000 of our users.

R. Emerging Technology: We are building an industry consortium to address medical problems leveraging technological advances. An example can be using Artificial Intelligence and Machine Learning to address predicting the utilization of beds, or developing a model to understand the emergence of a specific variant in a specific geography and the impact of these newer (hypothetical) variants on transmission, infectivity, and overall community-based impact.

S. Ombudsman:

We strongly encourage professional interaction and courtesies. We heavily lean on Evidence-based rationale, and we respect creativity. Our ethical values are foremost essential for us, and we cherish those with the highest order. We have identified Prof. Emeritus Dr. Manbar Rawat to resolve any residual issues if not resolved by the Founder.

All along, we have ensured that only hands-on experts are providing the knowledge transfer. We are not book-based academicians. Our experts have significant hands-on experience and expertise from their specialized domain. These experts’ work contributions are pro-bono, i.e., they do not charge us, and we do not reimburse them.

Funding: As of this writing, we the Founders, have funded all the initiatives. We have not received any funding from donations, advertisements, any pharmaceuticals, or any other industry. We have avoided all and any conflict of interest.

Scaling and Continuity: We will explore submission to foundations for support. If we secure funds for CovidRxExchange, we will announce that and develop Policies, Governance, Visibility, Transparency, and Audit/Accountability.

Slack: Slack is our global portal of Collaboration and Communication. However, WhatsUp is a transitory and stop-gap arrangement to support ease of communication.

Movers and Shakers: We will post the list of Several Movers and Shakers who make this initiative a throbbing success. Women, Budding Leaders, Technology Team and Operations team are few who make several things happen.

Our Founders (in alphabetical order of their first name):

Dr. Ajay Chaurasia, HOD Cardiology, Nair Hospital, Saifee Hospital, Mumbai Hospital, etc.
Dr. Anand Kawade, Pediatrician and Vaccine Authority, KEM Hospital, Pune and Vadu
Dr. Arvind Virmani, Molecular Scientist, Washinton DC.
Dr. Ashok Anand, Professor and Head, Gynecology and Obstetrics, GMC and JJ, Mumbai
Dr. Hemant Bhandari, Orthopedician, Mumbai Hospital, Mumbai
Dr. Pankaj Maheshwari, Chief of Urology, Fortis Hospital, Thane, Mumbai
Dr. Shashank Heda, Molecular Pathology and Technology Executive, North America

Humble Note: If inadvertently, we have missed a name, kindly bring it to our notice and we will credit them for their contribution. We request you to pardon for any of our omissions.

Absolute Isolation Works Absolutely

As of this writing the total deaths in the US have mounted to 10,335. Never before mankind had seen such a fast moving, swiping infection. We knew Ebola, we knew Marburg viruses, and a few Prion diseases but collectively, we had never faced such a dreaded disease with high mortality. We were caught almost unprepared or at least we ignored with complacency. I have shared my thought on why isolation is important to contain this disease and how countries like Singapore, South Korea and japan are dealing planning isolation and intelligence in dealing with this crisis.

Absolute Isolation Works Absolutely

As noted in my earlier blog, viruses are obligate parasites that need (MUST) a host cell to survive. They go through their phases of replication and eventually, after not getting proper host cells to infect, die a natural death.

Strict Isolation Social Distancing

I have had many folks across the geographies asking me a few questions?

  1. Why is the incidence of Coronovirus so high in the US?
  2. Are certain ethnicities (such as Indians) immune to the Coronavirus?

I will emphasize the control of Coronavirus based on the viruses’ obligate dependence on live cells for survival. We all know that if we practice Isolation absolutely, we should be assured of not having the disease.

Two situations preclude our ability for Isolation –

  1. Our needs for Essentials
  2. Fundamental Sense of Liberty

I owe you all a clear and concise write up on the best practices and pragmatic guidelines on “How to Manage Essentials” giving an end to end perspective, that provides the best way to avoid getting the virus inside your home. Give me until later this late evening to fulfill that commitment.

Let us talk about the “Sense of Liberty”. The US, the EU, and most developed nations have an enshrined fundamental Right of liberty to move.  Isolation or ‘Shelter in Place’ equals to ‘House Arrest’ for them. The later nullifies isolation and thus provides a continuation of the propagation of the virus by allowing it to jump from people to people (aerosol, airborne, contact and fomites).

Special intervention in community level

So after the rise of an emerging disease, goverments have a special responsibility to balance between civil liberties and special measures for protecting susceptible populations. However, three components of “scientific“, “voluntary” and civil liberty should be considered as guiding principles for decision-making and operating each special protective measure at the community level (cited).

Aerosols Airborne Fomites

I see a dichotomy based on the above two practical limitations that are increasing the spread of Coronavirus in the US. Select countries like India and Japan are strongly considering the imposition of emergency. Whereas, many have implemented strict isolation even if the idea of isolation has emerged from behind the Iron Curtain of China.

The Bhilwara Model

The Bhilwara Model for containment of COVID-19 refers to imposing a curfew in the district including suspension of essential services, extensive screening, and house-to-house surveys to check for possible cases, and detailed contact tracing of each positive case so as to create a dossier on everybody they met ever since they got infected. A similar model was followed in Singapore, South Korea, and Taiwan. Singapore had gone a step ahead and deployed its intelligence sleuths to extract the contact tracing, whereas, the draconian Chinese Govt deployed Bluetooth tracing abandoning the privacy laws (they do not exist in China, except while the couple is conjugating, I believe!).

The success of the Bhilwara model is attributed to controlling an outbreak within the first four days of the initial incidence (remember the Rho factor.

Absolute isolation works absolutely. Yes, it does but can we forego our sense of liberty? Can we minimize our needs and limit our consumption? Please visit my next blog on “Managing the Essentials”.


Also read – Support your service folks (maids, handyman, lawnmowers etc.)

Why is Coronavirus highly infective?

Additional Reading:

How do I know if I have a Coronavirus infection? Before reading further, I strongly advise and recommend that this should not be construed as advice. Your best recourse is your doctor or health care professional.

Doctors in China used a triage system for fast screening. This was published in the Lancet. Below flowchart from the Lancet.

COVID Symptoms Flowchart Lancet JPEG



. 2020; 8(1): e41.
Published online 2020 Apr 1.
PMCID: PMC7117787

Epidemiological and Clinical Aspects of COVID-19; a Narrative Review


The Spikes which you saw on the surface of the virus have a high affinity with a receptor on the human cells (ACE2). The direct implications are a definite attachment and infection of the cell. Once it has latched on to the cell, it infests and starts replication (reproduction).

Keeping my promise of sharing ACTIONABLE  INFORMATION, let me start with why COVID is so infectious.

Airborne Dispersal

MOSTLY, if not ALWAYS INFECTION:  After exposure to COVID-19 (Highly Infective). The Spikes which you saw on the surface of the virus have a high affinity with a receptor on the human cells (ACE2). The direct implications are a definite attachment and infection of the cell. Once it has latched on to the cell, it infests and starts replication (reproduction). Visit this Youtube for learning the virus replication.

What do I do as a common man?

Isolation (lockdown), using masks and following all CDC, WHO, NIH, State, and Local guidelines. Build a staging area outside the home, do not get the virus inside the home. All essentials should be cleaned appropriately before those get ingress into your home. Presume everything from outside is contaminated until cleaned.

2) Lysogenic phase: Breaking the cells after making thousands of copies (lysogenic phase). Please visit 

What do I do as a common man?

Clean after contamination. I follow the below steps – outer clothes removed in the Garage and set for laundry immediately, shower with soap/shampoo, nose blow, and peroxide gargles. The last two steps remove any adhered viruses from inside the nose and throat.

3) Early Symptoms: Step 1 follows in thousands of new normal respiratory cells. Fever, Nasal Congestion, loss of smell (because the olfactory cells are affected). Cells start producing exudate (copious secretions).

What do I do as a common man?

Get tested and isolate from other caregivers from the family and friends. Stay isolated (if mild symptoms and or test positive) until results are available or at the least 15 days after the lasts symptoms. If required, seek immediate help. DO NOT SELF MANAGE (explanation later).

4) Initial Phase of Lung Congestion: The virus travels inside to the Lungs and infects the respiratory lining cells. Visit the below video to learn more Also, see

5) Cytokine Storm: Huge secretion of fluids (doctors call this as Cytokine Storm) blocking oxygen exchange. Ventilators are required to support oxygenation. However, I have had first-hand reports that it is painful to watch patients struggling to breathe even on ventilators.

What do I do as a common man?

Seek early help, Please do not self-treat? Why – You may have a sudden catastrophic fluid collection in the lungs. What else do I do? Of course isolation and other guidelines to be used as required)

6) Acute Respiratory Distress Syndrome and Mortality/Morbidity: This is the most dreaded step.

What do I do as a common man? Be careful at the initial steps (1-3) (Shashank Heda, MD).

COVID19 Local Statistics

Rule of Thumb

Folks, my neighbor taught me one simple rule of thumb – What is essential? Can I survive without this? If I can, then it is not essential.


  • SPREADING AWARENESS (ask questions if required)


Stay Safe!

—    —    —    —    —    —


Based on the latest research from Nature and Cell BioSciences and analyzing the data (first hand) from Texas, I see it important to be all the stricter with isolation. Let me take a few issues individually.

Why SARS-CoV2 (COVID-19) is so dangerous?

Primarily because of the

1) Ridge on the S protein that allows it for tighter binding to the ACE2 receptor on the human cell
2) Suppression of antiviral immune response and
3) Concurrent activation of the pro-inflammatory response
Simply speaking – SARS-CoV2’s S protein (Spike protein) after binding with the ACE2 receptor on the human cell, changes its conformation to and goes into a tight affinity, primarily because of the ridge present on the S protein. That makes the SARS-CoV2 very infectious. Now, add to that, the florid inflammatory exudate (cytokine storm) and you get a double whammy. SARS-CoV is known to be exceedingly potent in the suppression of antiviral immunity and the activation of proinflammatory response.

Researchers are working to block the affinity of S protein or reduce the affinity. Another direction for research is controlling the cytokine storm. Our Milind is working on the Stellate Ganglion Block. You should bring him back here to ask more about them later.

Excerpt from Nature below (citations removed, reference link included) – A key to tackling this epidemic is to understand the virus’s receptor recognition mechanism, which regulates its infectivity, pathogenesis and host range. SARS-CoV-2 and SARS-CoV recognize the same receptor – human ACE2 (hACE2). SARS-CoV-2 receptor-binding domain (RBD) (engineered to facilitate crystallization) in complex with hACE2. Compared with the SARS-CoV RBD, a hACE2-binding ridge in SARS-CoV-2 RBD takes a more compact conformation; moreover, several residue changes in SARS-CoV-2 RBD stabilize two virus-binding hotspots at the RBD/hACE2 interface. These structural features of SARS-CoV-2 RBD enhance its hACE2-binding affinity. Additionally, we show that RaTG13, a bat coronavirus closely related to SARS-CoV-2, also uses hACE2 as its receptor. The differences among SARS-CoV-2, SARS-CoV, and RaTG13 in hACE2 recognition shed light on the potential animal-to-human transmission of SARS-CoV-2. This study provides guidance for intervention strategies targeting receptor recognition by SARS-CoV-2.

(Simplified – @ Shashank )

—    —    —    —

The origins of SARS-CoV-2 and COVID-19. To make a long story short, two parental viruses of SARS-CoV-2 have now been identified. The first one is bat coronavirus RaTG13 found in Rhinolophus affinis from Yunnan Province and it shares 96.2% overall genome sequence identity with SARS-CoV-2 [3]. However, RaTG13 might not be the immediate ancestor of SARS-CoV-2 because it is not predicted to use the same ACE2 receptor used by SARS-CoV-2 due to sequence divergence in the receptor-binding domain sharing 89% identity in amino acid sequence with that of SARS-CoV-2. The second one is a group of betacoronaviruses found in the endangered species of small mammals known as pangolins [4], which are often consumed as a source of meat in southern China. They share about 90% overall nucleotide sequence identity with SARS-CoV-2 but carries a receptor-binding domain predicted to interact with ACE2 and sharing 97.4% identity in amino acid sequence with that of SARS-CoV-2. They are closely related to both SARS-CoV-2 and RaTG13, but apparently they are unlikely the immediate ancestor of SARS-CoV-2 in view of the sequence divergence over the whole genome. Many hypotheses involving recombination, convergence and adaptation have been put forward to suggest a probable evolutionary pathway for SARS-CoV-2, but none is supported by direct evidence. The jury is still out as to what animals might serve as reservoir and intermediate hosts of SARS-CoV-2. Although Huanan seafood wholesale market was suggested as the original source of SARS-CoV-2 and COVID-19, there is evidence for the involvement of other wild animal markets in Wuhan. In addition, the possibility for a human superspreader in the Huanan market has not been excluded. Further investigations are required to shed light on the origins of SARS-CoV-2 and COVID-19



Demystifying Fasting and Cancer

All faiths across the globe different faith from Zoroastrians, Buddhism, Christianity, Islam, Judaism, Taoism, Jainism, and Hinduism advocate fasting. Fasting is definitely helpful for health and longevity. Social media is abuzz with Fasting and how it treats cancer. There is a sudden surge of colloquial and rudimentary messages on health. Often, these are relied with credence when it comes especially from revered spiritual leaders. One such message is from Sadhguru, a highly respected spiritual leader. In this video, Sadhguru is talking about the ubiquitously presence of cancer cells in our body. To deter the spread of these cancerous cells, he is recommending fasting.

First and foremost, we need to visit the definition of cancer cells. A key characteristic of cancer cell is uncontrolled growth of cells that have accumulated genetic changes (mutations) due to a carcinogen (a cancer causing agent). Second, cancer cells are not goondas that collect in one place as they advance. In fact, as the cancer stage advances these cells spread across their site of origin. Third, fasting is helpful only in select cases, not every cancer. Also, fasting is helpful beyond cancer, however it depends upon the state of metabolism, activities, age, at the least.

While we need people like Sadhguru to bring the social transformation, we definitely want these messengers to provide a solid rationale that is resting on scientific pedestals, devoid of which we will create confusion and loss of credibility. In this article, I have provided a scientific rationale for understanding the causes of cancer and if fasting can help stop the development or progression of cancer.

Words 2492, reading time 9 – 12 minutes. Background in Medicine helpful.

This 2.34-minute video from Sadhguru is truly insightful.  In the below article, I provided the rationale for reconciling scientific understanding of Cancer and Diet with those Vedic practices that are proposed by Sadhguru. More importantly, scientific literature provides a mixed body of the rationale for dietary practice for cancer prevention and or treatment. To rephrase, dietary restrictions can be a feasible option for select cancers, NOT ALL the types of cancer.

I got this video from Singapore, from a good colleague with whom I worked several years ago. With deep respect and reverence to Sadhguru. I listened to this video wherein Sadhguru talked about cancer as –

1) Always present within the body and get stimulated because of stimulants and intoxication.

2) They get organized into one place and later become overwhelming for the body to counter.

3) That these cancer cells consume 27-28 times the normal calories.

His solution according to Yogic culture is –

1) Spacing meals 8 – 12 hours a day

2) Fasting once or twice a month

It immediately drew my attention to the landmark paper by Hanahan and Weinberg, in which the authors talked about ‘The Hallmark of Cancer”. As an Oncology fellow, I remember having read it at least 2-3 times as it was foundational and disruptive in 2000.

As undergraduates, we were tutored on the existence of Oncogenes (1970) and Tumor Suppressor Genes (1986) and Knudson’s two-hit hypothesis (1971). Then, it might have not had such a reminiscent influence on my mind, until I started my post-graduation in pathology. However, Hanahan and Wienberg’s paper was a step ahead in explaining the different pathways for cancer. It served me when I lead the exploratory search for the epigenetics (methylation of TSG) and downregulation of several caspases (genes) in the apoptotic pathway.

I was definitely perplexed when I read the version of Sadhguru on the existence and or progression of cancer for several reasons –


  1. I mentioned the key developments in cancer as a stepwise accumulation of mutations in the genes of the cancer cell. These mutations occur due to several factors called carcinogens – viruses, chemicals, hormones, persistent inflammation, UV radiations, etc. We also know that cancer can occur de novo due to improper repair mechanism or existence of germline mutation (mutation inherited from parents). However, stimulants and intoxicants (especially the former), are definitely not carcinogenic and intoxicants like alcohol are considered co-carcinogens, not directly implicated in the development of cancer causation. I especially exclude the 300 plus carcinogens found in cigarettes as a stimulant and include nicotine as the stimulant, which is not a carcinogen, as proven by ‘comet assay’.

I realized, like thousands of other researchers across the globe, that tumorigenesis is a multi-step process and follows a multistep pathway. Germline mutations (those acquired from parents) like BRCA1, BRCA2 or RB genes occur in hereditary cancers. We can call these as existing in all cells in folks who inherit them from parents. However, the percentage of germline mutations are minuscule, possibly representing less one percent of the population. For these hereditary acquired cancers, one single hit drives a normal cell towards cancer progression. Where, in a normal population, any mutation has to hit two times to drive the cells to cancer progression. This Two hit hypothesis was proposed by Knudson in 1971 and is the underlying mechanism for most genetic aberrations occurring in a normal population. Of note, cancer cells do not exist universally in our bodies unless those are inherited from our parents (a less than 1% probability).

TSG and Cancer


  1. Though we know that cancer cells consume most of the host nutrition, it is hard to believe that these (cancer) cells organize (like gangs of Goondas) and rob the body of the nutrition. In fact, it is the other way around. Cancer cachexia, a state common in terminal cancer, is primarily due to diversion of nutrition towards metastasized (spread out) cancer cells, not when they come together.


  1. The solution offered by Sadhguru, that we should fast at least once or twice to avoid cancer is so much inadequate if not wrong,  as we all know that those who fast frequently have cancer and those obese who are voracious eaters don’t necessarily have cancer (but other metabolic diseases).


I specifically mentioned ‘The Hallmark of Cancer” that was published in 2000. This paper made a major stride in advancing our understanding of cancer (the paper was revised by Hanahan and Weinberg in 2011). It is worth revisiting the 6 facets of the hallmark in the above illustration.



Warburg Effect

Recently, a debate is intensifying on the existence of the mechanism of cancer causation other than carcinogen-induced genetic abnormalities. Immune modification and metabolic abnormalities have also been implicated. The later is called the Warburg effect. Warburg effect proposes that the cancer cells metabolize via the glycolytic pathway even in the presence of aerobic state instead of the much more efficient oxidative phosphorylation pathway.

Let us understand two aspects –

1) Does fasting help the initiation of cancer and

2) Once established and or advanced, will fasting help cancer to regress and or get into control?

Does fasting help cancer?

Recent Geroscience literature reveals that cancer and aging are characterized by dysregulated metabolism consisting of upregulation of glycolysis and down-modulation of oxidative phosphorylation. Based on the research on Geriatric patients, metabolic interventions have been explored as promising strategies to promote longevity and to prevent or delay age-related disorders including cancer.

Will fasting help regression and or control of Cancer?

Select metabolic intervention approaches include chronic calorie restriction, periodic fasting/ fasting-mimicking diets, and pharmacological interventions mimicking calorie restriction.  These are considered as adjuvant anticancer strategies, not the mainstay of cancer therapeutics. By adjuvant, I mean they are supplemented along with standard cancer therapy (chemotherapy, radiation, and targeted therapy). However, to summarize, calorie restriction is subjective and second, where it is effective, it has an adjuvant effect.

Animal studies (in rodents) have shown that chronic caloric restriction reduces and delays cancer incidence, and inhibits tumor progression and metastasis. Also, there is mounting evidence that cancer incidence and mortality are strongly reduced in chronic calorie-restricted non-human primates. Studies of long-term calorie-restricted human subjects have shown a reduction of metabolic and hormonal factors associated with cancer risk. However, chronic caloric restriction is not a feasible clinical intervention. Evident difficulties, such as the long period required to be effective, and unacceptable weight loss, hamper clinical application in cancer patients.

Autophagy: definition and mechanisms

In the 1990’s Yoshinori Ohsumi first proposed autophagy. He received a Nobel Prize in 2016 for Physiology or Medicine for his seminal work in establishing a morphological and molecular mechanism of autophagy.

Autophagy is an evolutionarily conserved lysosomal catabolic process by which cells degrade and recycle intracellular endogenous (damaged organelles, misfolded or mutant proteins, and macromolecules) and exogenous (viruses and bacteria) components to maintain cellular homeostasis. The specificity of the cargo and the delivery route to lysosomes distinguishes the three major types of autophagy –

  • Mircroautophagy involves the direct engulfment of cargo in endosomal/lysosomal membrane invaginations.
  • Chaperone-mediated autophagy (CMA) recycles soluble proteins with an exposed amino acid motif (KFERQ) that is recognized by the heat shock protein hsc70; these proteins are internalized by binding to lysosomal receptors (LAMP-2A) 6.
  • Macroautophagy (herein referred to as autophagy) is the best-characterized process; in this process, cytoplasmic constituents are engulfed within double-membrane vesicles called autophagosomes, which subsequently fuse with lysosomes to form autolysosomes, where the cargo are degraded or recycled. The degradation products include sugars, nucleosides/nucleotides, amino acids and fatty acids that can be redirected to new metabolic routes for cellular maintenance.

Autophagy occurs at basal levels under physiological conditions and can also be upregulated in response to stressful stimuli such as hypoxia, nutritional deprivation, DNA damage, and cytotoxic agents. Autophagy has attracted considerable attention as a potential target of pharmacological agents or dietary interventions that inhibit or activate this process for several human disorders, including infections and inflammatory diseases, neurodegeneration, metabolic and cardiovascular diseases, obesity and cancer.

Autophagy and cancer
The role of autophagy in cancer is complex, and its function may vary according to several biological factors, including tumor type, progression stage, and genetic landscape, along with oncogene activation and tumor suppressor inactivation. Thus, autophagy can be related either to the prevention of tumorigenesis or due to the enabling of cancer cell adaptation, proliferation, survival, and metastasis. The initial indication that autophagy could have an important role in tumor suppression came from several studies exploring the essential autophagy gene BECN1, which encodes the Beclin-1 protein that is frequently deleted in ovarian, breast and testicular cancer.

BECN1 is located adjacent to the well-known tumor suppressor gene BRCA1, which is commonly deleted in hereditary breast cancer. These deletions are generally extensive and affect BRCA1 along with several other genes, including BECN1, suggesting that the deletion of BRCA1, not the deletion of BECN1, is the driver mutation in breast cancer. Furthermore, the activation of oncogenes (e.g., PI3KCA) and inactivation of tumor suppressors (e.g., PTEN and LKB1) are associated with autophagy inhibition and tumorigenesis. Animal models note that the tumor suppressor function of autophagy is associated with cell protection from oxidative stress, DNA damage, inflammation and the accumulation of dysfunctional organelles. Collectively, these phenomena are important factors that could trigger genomic instabilities leading to tumor development.

However, the loss of function of autophagy genes has not yet been identified and demonstrated in humans, raising doubts about the relevance of autophagy to tumor initiation in different types of cancer. In addition, the autophagic machinery is not a common target of somatic mutations, indicating that autophagy may have a fundamental role in the survival and progression of tumor cells.

Once the tumor is established, the main function of autophagy is to provide a means to cope with cellular stressors, including hypoxia, nutritional and growth factor deprivation, and damaging stimuli, thus allowing tumor adaptation, proliferation, survival, and dissemination. Autophagy, by degrading macromolecules and defective organelles, supplies metabolites and upregulates mitochondrial function, supporting tumor cell viability even in constantly stressful environments. Studies have demonstrated that autophagy increases in hypoxic regions of solid tumors, favoring cell survival (a factor that does not favor fasting to help cancer regression and or cure).

The inhibition of autophagy leads to an intense induction of cell death in these regions. Moreover, tumors frequently have mutations or deletions in the tumor suppressor protein p53, which also favors autophagy induction to recycle intracellular components for tumor growth. Although the basal autophagy rate is generally low in normal cells under physiological conditions, some tumors show a high level of basal autophagy, reinforcing the prosurvival role of autophagy in cancer. RAS-transformed cancer cells undergo autophagy upregulation to supply metabolic needs and maintain functional mitochondria, which in turn favors tumor establishment. Autophagy also has a supportive role in metastasis by interfering with epithelial-mesenchymal transition constituents to favor tumor cell dissemination. Finally, studies have demonstrated that autophagy is commonly induced as a survival mechanism against antitumor treatments, such as chemotherapy, radiotherapy and targeted therapy, contributing to treatment resistance.

How does dietary restriction modulate autophagy and cancer therapy?

Autophagy and cancer therapeutics have a mixed relationship. Because autophagy can inhibit tumor development or favor tumor growth, progression, invasion and treatment resistance, researchers proposed that autophagy modulation could be a new therapeutic strategy in the treatment of some malignancies. In preclinical studies, dietary restriction (DR) has been shown to extend the lifespan and reduce the development of age-related diseases such as diabetes, cancer, and neurodegenerative and cardiovascular diseases. DR promotes metabolic and cellular changes in organisms from prokaryotes to humans that allow adaptation to periods of limited nutrient availability. The main changes include decreased blood glucose levels and growth factor signaling and the activation of stress resistance pathways affecting cell growth, energy metabolism, and protection against oxidative stress, inflammation, and cell death. Nutrient starvation also activates autophagy in most cultured cells and organs, such as the liver and muscle, as an adaptive mechanism to stressful conditions.

Studies demonstrate that dietary interventions can reduce tumor incidence and potentiate the effectiveness of chemo- and radiotherapy in different tumor models, highlighting dietary manipulation as a possible adjunct to standard cancer therapies. Among the many diet regimens that have been assessed, caloric restriction (CR) and fasting are the methods under intense investigation in oncology. CR is defined as a chronic reduction in the daily caloric intake by 20-40% without the incurrence of malnutrition and with the maintenance of meal frequency. In contrast, fasting is characterized by the complete deprivation of food but not water, with intervening periods of normal food intake. Based on the duration, fasting can be classified as –

(i) intermittent fasting (IF—e.g., alternate day fasting (≥16 hours) or 48 hours of fasting/week) or
(ii) periodic fasting (PF—e.g., a minimum of 3 days of fasting every 2 or more weeks).


Every stride in translational medicine helps in advancing our understanding of cancer and subsequently, the management of this malady. However, when a person of Sadhguru’s respected stature talks about fiction based on Yogic culture, we tend to degrade our Yogic culture and deprive the credibility of our repute.

However, as stated earlier, there is a mixed bag of information on dietary restriction and cancer prevention or treatment. 

There is a perfect need for interpreting a way of life (Sanatan Dharma and its various plural forms of ideologies for a living). I accept and understand that ancient Vedic science stood on significantly advanced scientific thinking, however, our times are different and we should rely on the current body of knowledge and refine our thinking of ancient yogic culture.

Note: I believe in providing direct feedback. I made an attempt to reach Sadhguru’s office at Coimbatore. No one answered. Possibly, I will make a few more attempts.


Effect of short term fasting on cancer treatment

Autophagy and intermittent fasting: the connection for cancer therapy?

Nicotine: Carcinogenicity and Effects on Response to Cancer Treatment – A Review (2015)


Surgical and Chemotherapy Options for Treating Advanced CRC

Basic understanding on Colorectal Cancer

If you want to learn basic anatomy and gather understanding on CRC and the different options, below sites have helpful information –

Introduction and review of anatomy of colon cancer

You may also visit

Selected Animations of Colorectal Cancer (CRC)

Above site has great animations and offers succinctly information on current Treatment Strategies –

  • Surgery
  • Radiation
  • Chemotherapy
  • Targeted Therapy

For Understanding the different molecular laboratory test required for colorectal cancer, you may click here.

Chemotherapy and Targeted Therapy Options (please click hyperlink)

Different options are given and you may want to discuss these with your Oncologists


Site helps us understand that it is a worthwhile effort to manage this, never a futile effort.

  1. Your metastatic tumors are limited enough to be removed surgically (resectable) and might be curable
  2. Your tumors are not resectable now, but with adjuvant treatment might become resectable and converted to a curable situation
  3. Your cancer is widespread and unlikely to become resectable and should be treated palliatively with the goal of extending your quality of life for as long as possible

I also saw other interesting content worth reading on this same site –


Chemo drugs for treating CRC

Current Options for Third-Line Treatment of Metastatic Colorectal Cancer

Surgical Options – Colorectal Cancer: Treatment Options

Approved by the Cancer.Net Editorial Board, 06/2016

You may want to consider chemo options per your case. Another Interesting Site that indicates Chemo Options per Stage

  • Stage I – No adjuvant treatment is recommended for stage I colon cancer.
  • Stage II & III – Adjuvant therapy is recommended for stage III and high-risk stage II colon cancer patients.
  • Stage IV – Treatment for stage IV colon cancer is generally palliative. There are many new cytotoxic chemotherapy and targeted agents available for treating metastatic colon cancer, such as 5-FU, oxaliplatin, irinotecan, cetuximab, and bevacizumab.

What is the cancer cells have seeded to peritoneum (abdominal cavity)?

Options for treating CRC that has spread to peritoneum are –

  • Old Traditional method such as
  • Newer Option such as

However, before we chose the options, we have to measure the baseline with scores. Socres are counted using two scales, Peritoneal Cancer Index (PCI ) and Peritoneal Surface Disease Severity Score (PSDSS). The scales compute information from three distinct parameters –

  1. Patient’s symptoms
  2. Location and
  3. CRC tumor burden (Size)
  • Older Methods – removal of the omentum, systemic and/or palliative chemotherapy, and palliative surgery.
  • Newer Regimen – cytoreductive surgery (CRS), hyperthermic intraperitoneal chemotherapy (HIPEC), and intraperitoneal chemotherapy.

Survival benefit –

Note: Older systemic chemotherapy regimens such as 5-flurouracil (5FU) and leucovorin offer a limited survival benefit of approximately 7 months, whereas, if Oxiplatin or irinotecan are added, survival can be extended to approximately 2 years.

Newer Regimens such as CRS and HIPEC have survival benefit of approximately 63 months with a 5-year survival near 50%. To say it simply, 50% patients will survive beyond 5 years.

The scales help in understanding the 5 years survival more objectively –

  • PCI 10 or less – 50% 5-year survival
  • PCI of 11 to 20 – 20% 5-year survival
  • PCI more than 20 – 0% 5-year survival

For Information on Gene Expression Profiling, you may visit following site –


The information available is for information purpose only. These are not recommendations. You are advised to consult your oncologist to get the recommendations for managing CRC patients.  The above site has all relevant references hyperlinked to the subtopics. The author holds no responsibility for any information mentioned herein.


CRC – Gene Expression Profiling

Molecular profiling changes the management of Colorectal Cancer significantly. This blog lists all relevant molecular markers associated with prognostic, response to chemotherapy, survival and recurrence of Colon Cancer.

Molecular profiling changes the management of Colorectal Cancer significantly.  This blog lists all relevant molecular markers associated with prognostic, response to chemotherapy, survival and recurrence of Colon Cancer.

The markers are chosen based on the basis of gene expression profile on colon cancer. As the cancer advances, it accumulates several genetic aberrations. Spread of cancer, response to treatment, survival to treatment and recurrence are all associated with different molecular markers.

These markers have been shortlisted from existing literature, experience with patients and the outcome. However, this is based upon my understanding and experience with patients and any decision based upon this blog need to be approved by your treating physician. I take no responsibility for decisions and or outcome based on these markers.

Many Molecular markers have been used for prediction and prognosis. Key amongst those are –

  1. MSI – Microsatellite Instability with the mismatch repair MMR system, MSI-H, MSI , MLH1, MsH2, MsH3, MsH6 and PMs2
  2. EGFR –
  3. VEGF
  4. KRAS mutation in Codon 12, 13, 61
  5. PTEN mutation
  6. PIK3CA Mutation
  7. BRAF V600E (Exon 15)
  8. p53


CEA – Carcinoembryonic antigen – CEA is separated from other molecular markers since CEA helps in understanding tumor burden and is also required for regular follow up.


Tissue Sampling:

The tissues should be immediately placed into liquid nitrogen upon excision and meticulously selected  pathologist for molecular profiling. Samples both from primary and secondaries (Lymph nodes) are required. Remember, to submit normal tissue along with the disease sample.

Dry Ice can be used as a media only for selected tests.

This page is under construction. I will update the markers as well as the references.

For Understanding the different surgical and chemotherapy options, you may visit –

Surgical and Chemotherapy options for Treating Advanced CRC, click here