Challenging cancer dogma in Mumbai

As an oncologist with a busy practice in the Indian city of Bangalore, I find myself frequently confronted by disappointed patients and their relatives, who ask me when we will finally find a cure for cancer. I evade and dodge some questions, and I answer others, hiding behind platitudes and power points to show that we are making progress in kicking this scourge on its heels.

But I cringe, because I know that envisioning a time when we’ll be able to cure almost all cancers, with an ever-improving stream of engineered pharmaceuticals and yet-to-be-discovered cutting-edge treatments, seems so naïve, so utopian…

Just like the seductive headlines I read on a daily basis, which reek of scientific bravado, bordering on hubris, as they inform us that a cure for cancer is just around the corner. I read them with a resigned shrug, staggering from the vastness of the problem – a game whose rules we don’t even understand, so we play checkers while cancer is playing chess – and I wonder aloud whether everyone is inhaling these half truths.

So I was thrilled when I chanced upon an editorial in Lancet Oncology co-authored by Rakesh Jalali, a neuro-oncologist I know rather well, who works at the venerable Tata Memorial Centre in Mumbai – easily South Asia’s leading cancer centre (Lancet Oncol 17:140–141).

The editorial captured my frustration with paltry victories against cancer and the preoccupation with the hype generated from so-called molecular and genetic ‘breakthroughs’ that are translating into neither a meaningful understanding of the malignant process nor a clinically relevant relief for our patients.

It also brought home to me how far cancer has become draped in ribbons of every hue, while we stand awestruck by the glitz and blinding promises of targeted ’omic therapies, seemingly forgetting that cancer remains a formidable challenge as ever.

On a brighter note, it flagged up a conference that promised to take a critical look behind the glitz. Titled ‘A Conference of New Ideas in Cancer – Challenging Dogmas’, it had been called by the Tata Memorial Centre to celebrate its 75th anniversary, and would be held later that month in the iconic setting of the National Centre of Performing Arts, on Mumbai’s famous Marine Drive.

The three-day meeting, supported by Lancet Oncology, the American Association of Cancer Research (AACR) and the US National Cancer Institute, promised an eclectic mix of several bold keynote addresses, symposia and lively debates.

So it was that I found myself among an interesting and diverse body of 1000 delegates, who converged on Mumbai from 23 countries.

The brief the organisers had given to the speakers was simple: we are unhappy with the little that has been achieved against the scourge of cancer; we find it difficult to sit complacently with this ‘rah–rah’ scientific culture, amplified in public media by headlines of war-cry-like rhetoric enshrined by the ever so sexy ‘moonshot’.

The meeting lived up to its title for sure – it stirred the pot, adding much-needed zing to the stale ale, and the science kept us glued to our comfortable seats from morning till early evening.

In essence it was about bridging the cancer divide – between the entrenched zeitgeist and starkly contrarian points of view; between seductive statistics and meaningful benefit to patients; between activity and achievement; between those who may naïvely believe that cancer can be conquered with their understanding of a piece of the molecular jigsaw and those who struggle at the fringes of traditional, often ridiculed, conventional cancer care.

Unlike most scientific meetings of this scale that are awash with industry money, this meeting by design steered clear of support from industry and special interest groups. The result – a nonpartisan  gathering that had the moral courage to address hard-hitting questions that are often forgotten in clouds of commerce.

Crisis in mainstream biology

A leitmotif that ran through this meeting was that there is a crisis in mainstream biology. The linear, deterministic computer models that grew out of our cultural fascination with the genetic code, beginning with the discovery of the DNA structure in early 1950s, no longer serve us well as explainers and predictors of modern biology and cancer. Yet no better alternative has yet emerged to make sense of things.

The first keynote speech, titled Cancer Research in Need of a Scientific Revolution, challenged the basis of our current understanding of the nature of cancer. Carlos Sonnenschein, from Tuft’s University, Boston, argued that cancer is a defect of tissue architecture, and that the predominant theories that see it as a cell-based disease could therefore be leading us up the wrong path. He argued the case for the ‘tissue organisation field theory’, which he has been developing over many years, alongside Ana Soto, his longtime colleague who holds the prestigious position of Blaise Pascal Chair at the École Normale Supérieure in Paris.

Dominant theories about mechanisms of DNA damage came in for critical scrutiny by Indraneel Mitra, director of the translational research programme at the Tata Memorial Centre. Another iconoclast venerated for his original thinking, Mitra proposed a new model which focuses on the patho-physiological role played by circulating fragments of DNA and chromatin, which act as DNA damaging agents when they are freely uptaken by healthy cells. These circulating fragments are released into the blood from dying cells during the programmed cell death process, apoptosis. The causal link proposed between these bits of biological detritus and DNA damage could throw new light on what causes cancer, and open up potential new avenues for prevention and treatment.

For those of us who live by the edict “In God we trust, rest please bring data,” the unassuming Ian Tannock from the University of Toronto, Canada, gave an engaging keynote on the relevance of randomised controlled trials in clinical practice. He exhorted the audience not to be over-impressed by a successful single trial, and to interpret practice-changing randomised placebo-controlled clinical trials with particular caution. “Repetition of important results is essential before changing practice,” and “clinicians should expect less benefit and more toxicity when applying the results of clinical trials in routine practice,” were his two central messages.

The profound, urbane Ronald DePinho, President of the MD Anderson Cancer Institute, Houston, gave a rousing keynote speech on The Cancer Moonshot – Making Cancer History. He detailed the monumental efforts of the US Government, and MD Anderson in particular, to conquer the scourge of cancer in our time. He surveyed the current landscape of available services at the MD Anderson, and talked about how investments in technology, personnel and time are pushing the scientific community  closer to an all-out cure.

His was a bold, exhortation – a tad political – that stood somewhat alone against the more sceptical, insistent view that we need to reassess our outmoded view of this disease. These sorts of claims about the death of cancer, aka moonshot, aka making cancer history, which seem to stand exposed by the triumphant march of this disease, are what prompted the organisers to call this conference questioning the grounds for such certainty. But DePinho’s sincere yearning for cure and commitment to getting the science right struck a chord with the audience.

The meeting closed with a lineup of the distinguished faculty taking the stage to deliver a circumspect but sobering narrative on the three-day marathon.

To me, the Mumbai conference on New Ideas in Cancer was a provocative, eye-opening preview of the glaring, and obvious cracks in the foundation of the war against cancer; a laudable effort by a handful of creative, intrepid, and bold academic clinicians, who are urging us to look where nobody else is looking.