World Cancer Day 2023 | Precision oncology is not a cancer test or drug, it's an orientation: Dr Sewanti Limaye

Dr Sewanti Limaye, Director, Precision Oncology, HN Reliance Hospital and Research Centre.

Cancer is among the most researched diseases in the world. For most cancers, early detection is rare, and there isn’t enough consensus among oncologists, researchers and practitioners of non-Western medicine on its exact causes. Overall, a few broad causes have been conclusively established: Cancer may arise as a consequence of genomic abnormalities such as mutations, or when the body’s immune system weakens or collapses, or due to external assaults to the body such as tobacco use, exposure to chemicals and radiation and certain infections.

But much like the human body, much of this disease is a mystery. There is no one cause and there is no one cure. As Pulitzer Prize-winning author and oncologist Siddhartha Mukherjee has written in his cancer magnum opus The Emperor of All Maladies, “That this seemingly simple mechanism—cell growth without barriers—can lie at the heart of this grotesque and multifaceted illness is a testament to the unfathomable power of cell growth. Cell division allows us as organisms to grow, to adapt, to recover, to repair—to live. And distorted and unleashed, it allows cancer cells to grow, to flourish, to adapt, to recover, and to repair—to live at the cost of our living. Cancer cells can grow faster, adapt better. They are more perfect versions of ourselves.” About researchers and oncologists, he says, “In Lewis Carroll’s Through the Looking-Glass, the Red Queen tells Alice that the world keeps shifting so quickly under her feet that she has to keep running just to keep her position. This is our predicament with cancer: we are forced to keep running merely to keep still.”

Globally, there’s been a fall in mortality rates of cancer, but the disease continues to thrive in all races and nations. The data from India is more alarming than ever before: The National Cancer Registry Programme Report 2020 estimated the number of incident cases of cancer in India for the year 2022 to be 14,61,427 (crude rate:100.4 per 100,000). In India, one in nine people are likely to develop cancer in their lifetime. Lungs and breasts were the leading sites of cancer in males and females, respectively. Among the childhood (0-14 years) cancers, lymphoid leukaemia (boys: 29.2 percent and girls: 24.2 percent) was the most prevalent. The incidence of cancer cases is estimated to increase by 12.8 percent in 2025 as compared to 2020. This report also concluded that in India during the Covid years, mortality rates due to cancer increased, reversing a downward trend before Covid.

Also read: Mediterranean diet can help fight and prevent cancer. Here's how

But the past decade has also witnessed some of the most hopeful breakthroughs in cancer treatment. Approach to treatment has changed prognoses and outlook. The buzz term in this ever-changing treatment landscape is precision oncology.

Precision oncology approaches treating cancer believing that all cancers are alike, but they are alike in a unique way. Two people with the exact same diagnosis can have different prognoses and different outcomes from treatment.

One of the most passionate, research-driven and articulate practitioners of precision oncology in India is Dr Sewanti Limaye. After completing her education and training at New York University, Harvard Medical School and the Sloan Kettering Institute, Dr Limaye returned to India and started as a medical oncologist at Kokilaben Dhirubhai Ambani Hospital, Mumbai. Later, she took over as director of Precision Oncology at the HN Reliance Hospital and Research Centre where she spearheads a revolution of sorts.

Also read: Cancer vaccine hunt makes progress, finally: Lisa Jarvis

In this interview to mark World Cancer Day, Dr Limaye talks about new frontiers and what could change treatment paradigms and the demand for new treatment paradigms in India in the near future. Edited excerpts:

Can you tell us what is precision oncology, how is it different from cancer treatment as we know it, including radiation, chemotherapy and surgery?

Precision oncology is not a drug or a test, it is an orientation, it is specialised way of looking at oncology diagnosis and management from specific lenses. It is a new way of looking at cancer diagnosis and treatment. Essentially, it’s trying to understand the cancer biology of a particular person's cancer and designing the treatment around it and came to be known as precision oncology.

So it's an approach, not a medicine.

Not a medicine, it's an orientation to that case. I call it personalised precision oncology. So personalizing therapies based on the precise knowledge of the tumor, of the stage, of what all treatment the patient has had, and what treatment would be getting the best outcome for that patient at that time. It's actually a cliche because that's how we should all be doing it, right?

Did this term come about at a particular point of research, is a group of doctors responsible for making this approach a practice?

I would say, from early 2000s in the US. Essentially, this happened with a malignancy called Chronic Myeloid Leukemia (CML), where there there is a genetic fusion named Philadelphia Chromosome which was a novel discovery in the 1960s, and then a discovery of a drug called Gleevec or Imatinib that could reverse the presentation and change the eventuality of that disease. The survival of CML cases increased to 90 percent and we now have survivors of that seminal clinical trial of over 30 years!

Then this whole scientific revolution in Precision Oncology played out, wherein we started looking at what was the genomic signature of a malignancy, whether it ran in the family, what is a particular cancer’s biologic signature. A big initiative called The Cancer Genome Atlas TCGA was formed. A huge number of researchers collaborated to give research samples of different tumor types. Genomic profiling made us understand the biology of that particular cancer since cancer is a genetic disease. Around that time, novel drug discovery was happening. And we realised that pathways could be targeted by these wonder pills.

Lung cancer became a poster child of Precision Oncology because there was a realization that a lot of the people don't develop lung cancer from smoking. Many lung cancer patients who had advanced disease, who had failed multiple lines of chemotherapy, if they were found to have that pathway were found to benefit from pathway directed therapy! It was like hitting a jackpot!

And you were in the US at that time. What made you want to come back to India and leave that exciting sort of world new dicoveries?

I wanted to come back to my family. But also, you always look for purpose in life. And I feel my purpose in life has actually become better defined now. There was only one passion that was integral to the way I practised oncology. And that was precision and that has truly become my calling. It is very critical for two reasons. One of course is for better cancer care delivery. If you figure out someone’s pathway or you figure out someone's biomarker, that is driving their cancer, you save time, energy, money, emotions, physical bashing, everything. But for the second reason also that it prevents you from a lot of waste. You can focus on things differently instead of putting down resources where they are not going to work.

What does the cancer treatment landscape in India look like at this point? What are some of the challenges you face?

First of all, when I started in my previous institution around 2016, there weren't enough labs doing these tests. And insurance in India won't cover your drugs. So every day is a challenge. But of late, very good Indian labs are coming up, they're doing excellent work and I am very encouraged by that. But drugs are still not available, insurance is still not covering. So sometimes you get frustrated and you think, why am I struggling in an environment that is so negative? But actually if you see the impact of what you do and realise it can touch many more lives in an exponential way, this amazing opportunity to really move the needle in India, serving your own people, and that desire doesn't die. We are at a juncture where the orientation needs to be reestablished in India. One of my key jobs is to bring awareness about Precision Oncology in India.

Are many more Indian oncologists embracing Precision Oncology, compared to say, five years ago?

Absolutely, there is no other way to go. I have figured out that awareness is what needs to be created. You have to increase the awareness to the to the limit that it becomes a need. That when the patient goes to see a doctor for cancer they themselves ask for the tests. I look at the young 25-year-old woman who walks into my clinic with breast cancer and in my mind I'm thinking BRCA, BRCA (the BRCA gene). So orientation is very critical. Why do I think that way? Because I have the orientation. So there has to be a splurge of awareness in all ways.

Is genomic testing also helping in more sort of what is the dangerous cancers like pancreatic cancer?

Yes, genetic pathways show up across the spectrum. Some cancers have more understood pathways, like lung cancer. For ovarian cancer, the Homologous Recombination Deficiency (HRD) panel testing has become a norm. Technologies are improving leaps and bounds every single day. We have newer drugs now which weren't available earlier. I say this all the time, I'm living in an imperfect time where the tests are evolving. The tests are not 100% and the application to that test result is also not 100%. But we have to do our best in these very imperfect times! We have to look for the silver lining! If I can save someone's life with these imperfect tests, I must give my best try!

The case of Sanjay Dutt, who you treated, and who has spokenextensively about his cancer journey is unique. What would you say was the reason for his successful treatment?

Mr Sanjay Dutt is a true inspiration. He is poster perfect example for Precision in lung cancer. He was told he had limited time but this is before we studied that he had bio markers for response with immunotherapy. The stage of a cancer is also relevant but to explore what kind of biomarker someone's cancer has, especially lung cancer, is most critical. Once we had figured out that he had a high expression of a biomarker called PDL1, we knew he may benefit from immunotherapy and he did. He is also very inspiring for his resilience, his tenacity and his courage. He continued to fight his disease throughout. He continued to exercise and work throughout his treatment. He was also very transparent about his disease and he did everything along with his family - his sisters especially Mrs Priya Dutt, his wife who has been a rock of support, his friends including Mr Paresh Ghelani have been with him every step of the way.

What about costs, you know, because a majority of Indians won’t be able to afford tests or the medicines. Some oncologists choose not to even mention this option to patients because they don’t want them to know this option exists but they can't afford it.

Yes, that’s the elephant in the room: Cost. The oncologist has the orientation, the patient has the orientation, but they can't do anything about it because they have limitation of cost. And that's where I think a unanimous voice to precision, a unanimous voice to individualizing therapy needs to come in. It has to be a movement that we need to then bring forward to the government. And we need to then also look at the demand supply equation. What is the demand-supply equation? I know pharma company-driven trials that are billion dollar trials running internationally, multinationally across the globe, but they don’t have enough subjects participating in these trials. Month after month, trials are going on unfilled. If such trials are brought to India, our patients could get access to novel cancer drugs for free!

Are there enough trials in India?

We ran 22 trials together and we are moving ahead with clinical trials establishment here as well, but that's just one center. I think there has to be a mass movement and I'm a big proponent of that. We run a compassionate drug access program. Say we find a rare pathway and the specific drug is not available in India, our team writes to wherever this drug is available. We have helped with thousands of dollars of medications.

You are also part of a group called Iylon. Tell me about what it is doing.

Iylon is a company that I co-founded with Dr Sendurai Mani who was formerly at the MD Anderson Cancer Centre and now he is at Brown University, USA. Very simply put, it is a way of communicating to the thought leaders in that specific disease condition to get the best opinion for a case. It is for oncologists as well as patients. Through Iylon, we have established a genomic analysis and a biomarker analysis channel also wherein patients can submit their records for review by global experts of his or her cancer type.

Realistically speaking, do you think cancer not as insurmountable now? What is the real difference you're seeing in terms of outcomes?

I definitely see the silver lining. The real challenges are mostly economical.

What are some of the breakthroughs we can expect in the near future?

I will speak broadly. Three things, essentially.

New pathway discovery, for which technologies are getting better each day. Earlier we were only looking at DNA, now we are looking at muti-omics.

The second is the continued novel drug development. So what we thought was there is a pathway discovery, and we went ahead and targeted those pathways. Then over the last decade, we realized that these drugs were only able to control the disease for so long. The cancer is smarter, it finds new pathways. So there are drugs that are meant for new resistant pathways that a particular cancer can take.

The third thing is the revolution with immunotherapy of all kinds. If you can't work through the tumor, you work through the body's own immune system. Or you work through both, you suppress the tumour and you enhance the body's immunity to eat up the cancer. We already have a class of drugs called immune checkpoint inhibitors, cancer vaccines are on the horizon and we are seeing CAR- T cell initiatives coming in a big way!