Paradox of Life
I met Dr Dilip Pawar by chance. But what a good chance it turned out to be. He is an oncologist turned clinical pharmacologist and a leading figure in the discovery of cancer drugs. A sagacious person of calm temperament, Dr Pawar worked with cancer patients throughout his career, especially the poor, and has seen suffering from very close quarters. I was surprised when he said that one out of every three cancer deaths in India is caused by poor diet, lack of awareness and failure to use cancer screening tests for early detection. All these factors are linked to poverty, which is also a barrier to accessing effective cancer therapies.
Dr Pawar comes from the poorest of the poor strata of society and grew up in Mumbai slums. His mother ensured that despite all odds he received a good education and he lived up to the challenge. A medical graduate from Grant Government Medical College and Sir JJ Group of Hospitals, Mumbai, Dr Pawar did his post-graduation from Lokmanya Tilak Municipal Medical College, Sion, Mumbai, in Oncology. He later pursued a PhD, Fellowship in Clinical Pharmacology from the University of California, and Global Clinical Research training from the prestigious Harvard Medical School, and it was the plight of the poor not getting good cancer medicines that drove him into Cancer research.
After working for some time in the industry, basically, to understand the dynamics of the global pharmaceutical industry where a few corporations hold the most patents, he did an MBA in Pharmaceutical Marketing at Southern New Hampshire University, Manchester, USA, and later worked at Nicholas Piramal India Limited, Dr Reddy’s, and Unichem. He is considered the final word in Clinical Research and Pharmacovigilance, dealing with the understanding and prevention of adverse effects of any medicine.
Our discussions, held over tea in my house, meandered from the treatment of cancer to the end stage of life. Cancer is inherently a chronic disease with well-understood risk factors. If it is diagnosed early, surviving it is not much of an issue anymore. Early-stage cancer that hasn’t spread and isn’t too big is more likely to respond well to treatment. The problem is early detection, and it is not a small problem. Tests used by doctors to identify and treat cancer are different from those used for cancer screening. When it comes to your body, you know it best. If you notice anything that isn’t normal for you, or if something doesn’t feel quite right, speak up. If colon cancer is detected at an early stage, more than 90% of patients survive the disease for 5 years or longer.
Our hospitals are overcrowded, doctors are overworked, and the poor have no means to go to a private medical practitioner. So, early diagnosis of cancer remains a buzz word and unless people are approached at the community level, it is impossible to have any early cancer diagnosis. Increasing the reach of life-saving healthcare initiatives is crucial, and mobile screening vans that offer cancer screening to individuals where they live and work is one important method to do this.
Working with Dr Chinnababu Sunkavalli and his Grace Cancer Foundation, Dr Pawar mobilized support for organizations donating buses and other equipment and what was once considered impossible happened. The fact that there is no end to medical research and there is always more to learn is one of its great advantages. Their work has shown that if you find cancer early, the treatment went from something complicated, expensive, and terrible to something that was relatively simple—simple meaning we were already in the minimally invasive world of surgery.
But what moved Dr Pawar most was the plight of the end-stage cancer treatment, which is basically no treatment but pain management and nutritional support. It is common for cancer hospitals to discharge such patients saying let them be at home, but the idea of a home is indeed grossly misunderstood. Dr Pawar remembers living his early childhood in Goregaon in Mumbai where 16 people were living in a 100 sq.ft. room. We must roll out a system of affordable palliative care. This would need social awareness, voluntary work, and above all, committed nursing professionals.
According to Dr Pawar, it is becoming more and more obvious that there will not be a single “cure” for cancer in the future. Instead, each patient will receive care that is tailored to meet their individual needs. But for personalized medicine to become a reality, we must have a wide enough selection of medicines to address every type of cancer. Personalized vaccinations, cell therapy, gene editing, and microbiome treatments are four technologies that will transform how cancer is treated, according to Dr. Pawar.
By comparing the DNA sequences of the tumor and of healthy cells, it is possible to identify multiple cancer mutations and select the ones that are more likely to provoke a strong reaction from the immune system. The vaccines are administered as messenger RNA, a molecule that tells cells how to make a specific protein, in this case, a cancer antigen that strengthens the immune system’s defence against the tumor. Unlike with gene editing, vaccines do not directly edit human DNA, but just provide the message. Another advantage is that the production of messenger RNA is cheaper than that of other cancer treatments. In can be done. It can be done in India. And it will be done, according to Dr Pawar.
In 2018, US FDA approved cell therapy for cancer. Immune T-cells from the patient are taken and genetically modified to target a particular tumor antigen in a procedure known as CAR-T cell therapy. By engineering T-cells to carry a molecule, borrowed from another type of immune cells called natural killer cells, with the capacity to target 80 per cent of cancer cells, each patient will be treated by his/her own cellular material. Though CAR-T cell therapy is promising, these are still in the early stages of clinical trials and will need a few years before they can reach the market. Dr Pawar points to the PI hospital system, which is taking a global approach in the concurrent development and dissemination of CAR-T cell therapy.
CRISPR/Cas9 has already changed the field of gene editing by making it much simpler and faster to modify DNA sequences with high precision. It is very much doable to use CRISPR gene editing to remove a gene from immune T cells that encodes a protein called PD-1 that tumor cells can use to evade an immune attack. Dr Pawar even envisions off-the-shelf CAR-T cell therapy that is sourced from donors. By making two edits to the donor T-cells- to attack only cancer cells versus indiscriminately attacking the patient’s cells, and to cloak the T-cells so they don’t appear foreign to the body and deliver a more robust reaction, cancer can be effectively treated.
But perhaps the most exciting is going to be oncologists teaming up with microbes. In inflammatory disorders like cancer, the microbiome can help to stimulate an immune system that has been repressed and to regulate an overactive immune system. As our knowledge of the interaction between the immune system and the gut microbiome grows, we know that within the microbiome there are peptides that mimic antigens on the surface of tumors. These can be used to make the tumor visible to the immune system again.
The paradox of life is that it carries death with it as a body moves around with its shadow. Both are inseparable. But by having more light, shadows can be less frightening. Dr Pawar’s son has already become a medical doctor and he is doing his integrated master’s in Spain. His daughter is in architecture school and one of her dreams is to design an end-stage living module. May Dr Pawar’s tribe increase!
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