Indian Cancer Atlas: Urgent unmet need for integrated approach in medicine

Disclaimer: My mentor wrote this post in ET Prime. I will only touch on the key specific issues which I felt that needed to be addressed in further detail. The article is behind the paywall. I can gift it if you need the access to read it completely. Please email me your requests on contact (at) myfastmail dot com.

Vikas Dandekar writes:

Using granular data, cancer is now being viewed from a new angle. Researchers in India are looking at the root causes of how cancers develop through mutations or over-activation of certain genes, which then stealthily evade the body’s defence mechanism. Premier Indian government research institutions, scientists, cancer specialists, and private-sector players have teamed up to set up the Indian Cancer Genome Atlas (ICGA). Experts say the not-for-profit initiative can go a long way in early identification of the causes of cancers, marking a seismic shift from the current treatment paradigm.

The press release for IGCA states that the consortium aims to achieve the goals under TCGA program.

Delivering the keynote lecture on Team Science in India,DG, CSIR Prof Shekhar Mande underlined the importance of scientific team building from diverse backgrounds in strategizing a coordinated response. He noted that establishment of Indian Cancer Genomics Atlas (ICGA) is a much needed initiative and will add value to India and to the world of science in terms of cancer treatment. Dr. Jean Claude Zenklusen (Director, TCGA, US-NCI) delivered Keynote lecture on the Cancer Genome Atlas- A Model for Team Science. Oncologists, Researchers, Scientists, and Academicians from India, USA, UK and Bangladesh are participatingin international conference inaugurated today.

These two write-ups need to be understood in the context of “genomic-optimism” and how it has sucked up millions of dollars in research budgets while refusing to address a simple premise- cancer is fast assuming a life-style disease.

Here’s a realistic check point from The Cell.

Cancer forms a small part of the spectrum and in the era of disease competing attention, I think there is an “over-reliance” on the promises for cancer treatment. Much of it is our ongoing fascination for “targeted therapies” with terms like “precision medicine” conveying the opposite of what actually happens. Cancer treatment (especially chemotherapy)- partially represents a scattershot approach (especially in the case of locally advanced or advanced metastatic presentations in Stage IV disease). In layperson’s terms, you block one pathway and cancer eventually progresses from another. Therefore, the emphasis throughout the article on early diagnosis and prevention.

This “variety” of genome pool in the Indian subcontinent has to do with an increasing interest from research consortiums as VD puts it succinctly:

Although opinions are divergent on pooling of Indian genes, scientists believe the diversity of Indian population is often in variation to that in the western countries, which makes it important to have a dedicated base of Indian cancer genomes.

It brings in further hackles to safeguard the intellectual properties related to genomic sequences because this data is extremely valuable.

Going back to the linked article from The Cell, here’s what the authors have to write:

This sounds like success — why are we so unhappy? It is worth taking a step back and asking: for what reasons do we want to investigate the genetic basis for common human diseases in the first place? One motivation is risk prediction — that is, using genetic factors to better stratify which individuals are at higher risk for specific common diseases, which may facilitate preventative measures and/or the better allocation of resources across a heterogeneously susceptible population. A second motivation is target identification, grounded in the view that our historical approach to understanding the pathogenesis of common diseases has been largely ad hoc and therefore prone to false positives and negatives. In contrast, GWAS provide a systematic, genome-wide approach for identifying genes that play a role in each disease. As this should result in a longer, higher-quality list of potential drug targets, GWAS were/are expected by some to accelerate our ability to develop effective therapies.

Can we really “prevent cancers” at the population level?

So what has gone wrong?

 The genetic component of common human disease risk consists of an extremely large number of variants of small effects, the vast majority of which would require astronomically large study sizes to definitively implicate. A subset of these weakly associated variants achieve genome-wide significance, but the effect sizes are usually modest even for these, and they have limited predictive power whether taken individually or considered together.

There is an additional case of discussion for cancer genomics and targeted therapies- ones that only prolong survival by a few months. My personal experience with a few of the labs bears testimony to their marketing efforts around “genome combination” which is based on a few reports published in western journals. A comprehensive review with measurable clinical outcomes is sorely lacking. This nonprofit would aim to correct the systemic deficiencies related to missing colossal data but then to what effect? This should also address a pressing concern in the “genomic reports” which comes with an array of disclaimers. As combinatorial therapies are often lacking for the specific genomic subsets- how do we as clinicians become wiser? It also opens up an additional source of anxiety for the hapless family who then fall in the spiral of endless opinions and certain cases leading to a delay in the start of definitive therapies.

The way forward is an integrated approach- focus on prevention and improve delivery through the palliative approaches (ironically through an improvement in access to opioids). Cancer treatment requires a comprehensive approach for quality of life paradigms, a holistic nutritional approach, improvement in weight loss strategies and socio-cultural measures to provide an integrated approach. I also hold a firm belief that healthcare should be delinked from the state governments and have a quasi-federal structure for Indian dominion to address the systemic shortfalls. A direct subsidy through “Ayushman Bharat” has little meaning when the government seeks to impose higher taxations on tobacco and alcohol, instead of banning the use of smoked and smokeless tobacco.

I don’t want to end the blog post on a pessimistic note. Here’s the quote from my teacher and I concur:

While such initiatives take time to gather critical mass and may not yield blockbuster drugs, Sarin emphasises that they lay the foundations for future therapies. According to his estimates, gene mapping has made a clear difference in the clinical management of about 5% to 10% of cancers like lung cancers. Genes that were not previously known to be associated with cancers are now deeply studied for their cancer-causing attributes, he says. “The human genome project provided the earliest road map. Now, ICGC and TCGA are getting into the finer aspects.” 

We need to take a long-term view, but an aggressive posturing and over-selling of the potential of gene therapies will lead to improper short-term objectives. The promised la la land of “personalised medicine” will mature with the foundational aspect of integrated medicine and a system to quantify the effects of treatment. It should go in parallel with the integrative approach (vide supra) and provide an impetus for systematic clinical trials.

Last but not the least. Dr Badwe (an eminent surgical oncologist) clearly mentions the high cost of access:

“New technology or data should help find drugs that can be made available at a reasonable cost and are not allowed to be patented. The social responsibility of valuations is lost, and the economic side is in crisis when it comes to drugs,” Badwe says.

The question of medical ethics has been raised too:

Another tricky issue in getting data in a country like India is compliance with medical ethics and patients being informed and taken into confidence about the process of tests. As R Ravi Kannan, an oncologist from Assam says, the ICGA project needs to establish synergies between scientists, clinicians, lawyers, and health economists. 

The Indian Genome Project raises some fundamental questions, and I hope we can address them in their entirety.