In 2017, Jasmin David was 48 years old and living in Manchester, UK, when she was told she had just a few months to live. She was diagnosed with an aggressive triple negative form of breast cancer. The following year, she underwent six months of agonising chemotherapy and a mastectomy, followed by 15 cycles of radiotherapy.
In 2019, her cancer had returned to spread to other organs. The prognosis was poor. But in July, David was declared ‘cancer-free’ by doctors after a two-year clinical trial at the Christie Hospital, Manchester. Her saviour was an experimental medicine combined with immunotherapy drug Atezolizumab.
Closer home, in a landmark move last week, India announced its first indigenously developed vaccine, Cervavac, for the second-most common cancer of women in India, cervical cancer. Developed by Serum Institute of India, it will be launched later in the year and is reported to be priced between Rs 200 and Rs 400. Calling it a breakthrough, Dr Aju Mathew, cancer researcher and medical oncologist with Ernakulam Medical Centre, Kerala, says, “It will help make the vaccine affordable, so we can prevent large numbers of highly preventable cancer.”
Whenever a new cancer miracle story hits the headlines, Dehradun resident Kunal Kumar Das becomes nostalgic. In 1996, he was a scientist with the Indian Space Research Organisation. When he was diagnosed with stage-I cancer, he had never heard about immunotherapy. “I was lucky 26 years ago to recover just by the removal of my left kidney. But, today, immunotherapy has evolved significantly. Life doesn’t end with diagnosis,” Das observes. He should know. In June, Das scaled a 11,830-ft mountain peak in Uttarakhand, and actively participates in initiatives for cancer survivors.
It is 2022 and cases such as David’s or Das’s are becoming more common than ever before. In June, oncologists from Memorial Sloan Kettering Cancer Center in New York released the results of a landmark trial, in which the drug, Dostarlimab, administered intravenously every three weeks for six months left all 18 patients cancer-free. “This is one of the best trial outcomes one can get. This means all rectal cancer can be cured using this therapy,” says Dr Anguraj Sadanandam, director, the Centre for Global Oncology, and head of the precision medicine team at the Institute of Cancer Research (ICR), London. In spite of the small targeted group, the results provide cheer.
Cancer continues to be the leading cause of death worldwide and, according to WHO, accounted for nearly 10 million deaths—one in six—in 2020 alone. The Cancer Statistics Report states that cases in India increased at an average annual rate of 1.1 to 2 per cent between 2010 and 2019. According to the latest Indian Council of Medical Research (ICMR) report, 29.8 million Indians are projected to be cancer-hit in 2025, up from 26.7 million in 2021. But winning the fight against cancer stands a good chance today.
WEAPONS OF HOPE
Somewhere between detection and cure, sparks of optimism keep appearing in research and clinical trials. The urge to play god is a frequent compulsion in the scientific community. Cancer gladiators are no exception. One of the biggest breakthroughs in cancer treatment this year is a ‘one-size-fits-all’ pill that was once considered a fantasy. Enter ERX-41, a lab-created protein with the power to destroy hard-to-treat cancers such as the breast, pancreas, ovaries and brain. ERX-41 protects healthy tissue even as it exploits the weaknesses in breast cancer cells to kill the tumours. A new experimental Swiss technology, SHREAD, activates the body to produce therapeutic agents at the precise location of infection.
It was developed by genetically modifying the common respiratory virus adenovirus, to get tumours to commit suicide—SHREAD tricks the nasty growth to create self-destructive agents.
Oncologists are witnessing light at the end of the tunnel: a team of engineers, physicists, neurosurgeons, biologists and immunologists have discovered a new form of photoimmunotherapy that makes cancer cells glow during an operation, for surgeons to identify and remove easily—often, some of these are missed that leads to a return. Experts believe that photoimmunotherapy will be the world’s fifth major cancer treatment after surgery, chemotherapy, radiotherapy and immunotherapy. The principles of warfare are being deployed by cancer fighters. Seek and destroy, mask and kill, identify locations to be bombed, infiltrate and exterminate, and spying are tactics used by the Sun Tzus of cancer wars.
The ‘mask it, kill it’ strategy has its fans—cytokines are drug proteins that train the immune system to kill tumours, but also have serious hepatic side effects. Biochemists ‘masked’ the drugs with caps, which can be removed only by tumour-sensitive enzymes that in turn reactivate cytokines, which stimulate nearby T cells to attack the tumour. Researchers have successfully implanted drug-producing beads around the size of a pinhead next to tumours to release T-cell activating agents.
Cancer cells are extremely wily and capable of executing fatal heists by hijacking macrophages—the cells that destroy any intruders. A team of researchers at the Advanced Organ Bioengineering and Therapeutics in the Netherlands led by Dr Jai Prakash has designed nanoparticles that can zone in on immune cells and provoke a revolt against cancer. Though most of these new therapies, drugs and devices are currently in the experimental stage, the promise has revealed itself; yes, cancer can be beaten once and for all.
THE IMMUNITY PARADIGM
Sanjay Dawar is an ambassador of hope for his doctor. Whenever there are cancer patients who are scared to be treated, doctors at Fortis Hospital, Gurugram, reach out to him. Dawar, a Delhi-based businessman who recovered from stage-1 lymphoma cancer in 2017, had undergone 16 sessions of chemotherapy between 2017 and 2018 followed by 22 radiations to his face.
“I went into depression for a long time. But Dr Ankur Aggarwal, who treated me, shared cases of cancer-affected children and stories of their resilience. These helped me bounce back. Now I counsel patients when they lose their will to fight,” he says. Early detection in Dawar’s case helped, but not everyone has luck on their side or even gets disease-specific treatment.
One of Dr Sadanandam’s soon-to-be-published studies is around developing a bio-bank to understand the difference between the immune system of tumours of Indian patients and those abroad. “Since immunotherapy is expensive, we need to know if it will work or not for patients who can’t afford it. Sometimes a clinician faces the dilemma of having to pick the appropriate patient for just one available drug. My study will help them choose. Luckily, there is no major difference between the cancers. Treatments available in the West can be used in India too,” he adds.
Even in the toughest prognosis, positive developments are possible now more than ever. Take, for instance, the recent breakthrough in pancreatic cancer research. It’s one of the deadliest cancers, with a 7 per cent survival rate for five years and a bit more. ICR scientists have successfully controlled and reversed its effects using gremlin therapy.
In April, ICR London revealed early results of a Phase I trial, where the immune system’s ‘natural killer cells’ were found to be effective in treating a third of patients with advanced cancers such as the bowel and lungs. Even though the treatment is highly experimental, researchers are excited by its potential. As clinical researcher Dr Juanita Lopez highlights in her study: “It does not have to be personalised for each patient like CAR T-cell therapy, so it could potentially be cheaper and faster to use, and might work against a wider range of cancers.” CAR T-cell therapy is a type of treatment in which a patient’s T-cells (a type of immune cell) are changed in the laboratory, so they will bind to cancer cells and kill them.
UNLEASHING BESPOKE BLOWS
Growing research around Precision and Personalised Medicine (PPM) indicates that novel cancer treatments could overcome reservations about the specificity of chemotherapy. “Even though chemotherapy has its uses, it is not precise. Instead, we want a precision-guided approach. One of those is immunotherapy, which uses the body’s own immune system to fight disease. In future, cancer cure will become a personalised paradigm,” affirms Dr Roy Herbst, deputy director for clinical affairs at Yale Cancer Center. PPM has made it easier to find specific gene mutations leading to tailor-made therapies.
“This has minimised side-effects while maximising efficacy. For instance, lung cancer had a dismal prognosis just a decade ago. Finding new protein targets in cancer cells has allowed us to hit them with specific medicines,” says Dr Srinivas Chakravarthy Gummaraju, medical oncologist and haematologist, Apollo Health City, Hyderabad. Another example is breast cancer which has specific medicines for protein targets. “Due to this, patients with advanced cancers are now able to live longer,” he adds. A recent study published in the European Urology Journal found that patients with advanced prostate cancer have a better chance of survival if treated with a targeted drug in addition to chemotherapy.
“With advancements in treatment, the severity of side-effects has decreased. Latest immunotherapy treatments have minimal side effects compared to chemotherapy or radiation,” says Samara Mahindra, founder and CEO of CARER, an oncology care company that provides customised nutrition and integrative therapies to cancer patients. Mahindra started the centre after her mother was diagnosed with cancer and she found little alternative support outside of traditional medicines. Centres such as CARER have come as a boon for patients who concur that the battle is often lonely and tiresome. “CARER helped me get my haemoglobin levels on track through guided nutrition. I knew my battle against cancer can’t be just won through medicines; I needed holistic support,” says Sindhuja Swamy, a 49-year-old Bengaluru resident, who was diagnosed with triple-negative breast cancer and underwent
chemotherapy followed by surgery and radiation.
HELPING WOMEN IN PERIL
The primary focus of treating cancer in India revolves around early detection. It has been successful, too. Earlier this year, Cancer Institute, Adyar, published the results of early diagnosis of breast cancer using a blood test. “Once larger studies confirm the findings, this blood test would play a key part in breast cancer diagnosis. Routine mammograms are low in cities while there is little access to such facilities in rural areas.
A blood test will solve this screening problem in both big and small hospitals,” says Dr T Rajkumar, head of molecular oncology at the institute. It is currently in talks with an industrial partner to formalise the procedure. “We’ve applied for a patent in India,” he says. The institute in partnership with IIT Madras is also developing a kit for the early detection of ovarian cancer.
Breast cancer is the most common type of cancer in women; bad news from Cytecare says one Indian woman is diagnosed with breast cancer every four minutes. WHO has better news—66 per cent of such patients survive for at least five years after diagnosis. Enhertu, an experimental drug developed by researchers from AstraZeneca and Japanese pharma giant Daiichi Sankyo, provokes antibodies to zero in on breast cancer tumour cells before dumping a cargo of chemotherapy on the spot.
Now, triple-negative breast cancer accounts for 10-15 per cent of all breast cancers, affecting 225,000 women worldwide and only one of 10 patients survive. The Acetic Acid Test developed in India is a low-cost, easily accessible way of screening for cervical cancer. “We take pride in manufacturing low-cost generic molecules and ‘bio-similar’ medicines. Several of them are as effective as the expensive original molecules manufactured by Western pharma giants,” says Dr Gummaraju.
The development of Cervavac also underlines the role of the Department of Biotechnology in facilitating trials and investments in the vaccine candidate, says Dr Rama Joshi, principal director and head, gynae oncology and robotic surgery, Fortis Cancer Institute, Gurugram. “Easy availability of the vaccine will provide larger database for researchers to focus their studies on various aspects of cervical cancer prevention. Since it will be an indigenous vaccine, the production can be tailored as per our requirements, ensuring easy availability and reach to the rural areas,” she adds.
SEEK AND DESTROY
Cancer research has evolved into offering cures with fewer side effects. “Immunotherapy seldom troubles other parts of the body. We’re in an era of targeted therapy while surgical procedures improve. There is robotic surgery and proton therapy. Radiation has become much better with magnetic resonance imaging, says Dr Nitesh Rohatgi, senior director, medical oncology, Fortis Memorial Research Institute, Gurugram. John Hopkins Medicine defines proton therapy, also known as proton beam therapy, as “a radiation treatment that precisely delivers a beam of protons to destroy tumour cells.
Compared with traditional radiation, protons allow doctors to better target radiation to the size and shape of the tumour, sparing the surrounding healthy tissue”. Nalla Srinivas swears by it. The therapy helped his 14-year-old daughter who had brain cancer to get back on her feet. “In 2019, our world turned upside down when we were informed of our daughter’s brain tumour. She was diagnosed in the third stage and had two surgeries. Instead of radiation, we chose proton therapy. Though expensive, the benefit of not having side effects outweighs the cost,” says Srinivas, a Hyderabad-based entrepreneur, whose daughter was treated at the Apollo Proton Cancer Centre in Chennai.
According to experts, proton therapy works best in brain tumours, pediatric cancers, neck cancers and prostate cancer. “For most early cancers, surgery and radiation therapy are definitive treatments, with chemotherapy as an adjunct. In advanced cancers, chemotherapy is the systemic therapy, and surgery and radiation are adjuncts. Radiation therapy is used in 60-65 per cent of cancer patients at some point, but there is always the worry of side effects. But proton therapy is so precise that it destroys tumour DNA more efficiently,” explains Dr Srinivas Chilukri, radiation oncologist at Apollo Proton Cancer Centre.
HIGH COST AND POOR CREDIT
The developing world, including India, cannot afford the cost of new expensive treatments. Hence, pharma giants do not invest heavily in research in third-world countries since they would have to price their products high to make a profit. “Not to mention the red tape and bureaucratic regulatory process, which are also huge hurdles for them,”
Dr Gummaraju points out. The palliative care model in Kerala has received widespread international attention. “India’s major achievement has been producing scientists and doctors who have left its shores to do stellar work abroad,” says Dr Mathew, adding that the trend speaks of the research environment abroad and the lack of meritocracy at home.
According to the WHO, one in every 10 Indians will develop cancer in their lifetime and one in 15 will die of it. While Western breakthroughs make the headlines, is the research element in India missing in cancer conversations? “We are not doing much to stretch the frontiers of cancer research. Most of our work centres around reverse engineering. While it’s important in bringing down treatment and care costs, it isn’t newsworthy,” says Dr Mathew. According to him, most of India’s achievements have come out from the Tata Memorial Centre. “This is primarily because of the heavy research funding it gets via the Department of Atomic Energy, enthusiastic researchers, and a large panel of willing patients,” he says.
The logistics of trials never match the funding because large-format trials run for decades. Dr Rajendra Badwe, director, Tata Memorial Centre, suggests that the government should allot more money to lengthen research funding beyond the present three years. “We should get support for five years, to be extended for another five, because cancer-related research takes at least that many years to give early results and 10 years for long-term outcomes—which are important if we have to make any difference globally,” he offers. There are the apologists and contrarians.
“What you’re seeing in the West is not exceptional. In the last decade and a half, whatever new drug has been approved by FDA has come in partnerships with pharma. The benefit to patients is just a few more months of survival. The cost in India would be around a few crore rupees for similar treatment,” says Dr Rajkumar. He points out that barring a few diseases (lung cancer survival rate went up to two years), there is no major long-term gain—“such drugs are not going to benefit countries such as ours because Indians are unlikely to spend their life savings for just a few more months of life.”
Dr Rajkumar seems to be missing some points. Regulators in the UK have approved a ‘search and destroy’ treatment for advanced prostate cancer. Pluvicto, an intravenous drug, acts like a missile that tracks down cancer cells and delivers a radioactive payload to bomb them to death. All 12 patients in clinical trials, who underwent six months of experimental rectal cancer treatment, went into remission without chemotherapy—a first in oncological history. Because cancer is not static, it is an incredibly difficult disease to treat. “It changes its characteristics from time to time. Majority of the time we don’t know how it will look in a patient. So genomic research needs to be pushed more,” says Dr Sadanandam.
In India, expensive drugs are not an option for many. “For most patients, these advances mean nothing,” says Dr Mathew, whose analysis of the financial toxicity of cancer was published in the Lancet Medical Journal last year. But, he is quick to point out that for a rare minority of patients, they offer immediate hope. He laments, “Unfortunately, they are people who can afford the treatments, or are lucky enough to get early access to some groundbreaking therapies.”
DEVELOP OR PERISH
The scenario seems to be changing. FDA-honoured Bengaluru-based scientist Rajah Vijay Kumar’s Cytotron is a breakthrough device in cancer care. Developed at the Centre for Advanced Research and Development in Bhopal, Cytotron destroys uncontrolled tissue growth by blasting the cancerous area with fast, high-energy short radio bursts. It is in use in the UAE, Mexico, Malaysia and Hong Kong.
ImmunoACT, developed in IIT-Bombay and now backed by Hyderabad-based Laurus Labs, claims to cure cancer at one-tenth of the cost of Rs 20-30 lakh per patient compared to Rs 4 crore in the US. Oncologists in India want the focus to be on lifestyle modifications, early detection and ease to palliative care. “Two-thirds of cancers in India are preventable. We will be better off if we tackle preventable cancer. For instance, early low-cost screening for breast, cervical and mouth cancers will reduce them by 30 percent,” says Dr Badwe.
A point stressed upon by Dr Rajkumar too. “Let’s not forget the socio-economic shift that reduced cervical cancer in people has increased incidences of breast cancer.” There’s light at the end of the tunnel, but it’s a long tunnel, says Dr Roy, adding, “the fact that these drugs work is good, but that they work in only a few patients is also good because we can find more about areas we must focus on”.
As for David, she is ready to celebrate her 25th wedding anniversary this month. Then there are plans to visit her hometown in Kerala. A place she visited three years ago to bid her final goodbye after doctors gave her 10 months to live. Today, it travels as an anecdote wherever she goes.
Stories of Strength
“I went into depression for a long time. But Dr Ankur Aggarwal, who treated me, shared cases of cancer-affected children and stories of their resilience. These helped me bounce back. Now I counsel patients when they lose their will to fight.”
Sanjay Dawar, a Delhi-based businessman who recovered from stage 1 lymphoma cancer in 2017
“I was lucky 26 years ago to recover just by the removal of my left kidney. But, today, immunotherapy has evolved significantly. Life doesn’t end with diagnosis.”
Kunal Kumar Das, who was diagnosed with stage-I kidney cancer in 1996. In June, he scaled a 11,830-feet mountain peak in Uttarakhand, and actively participates in initiatives for cancer survivors.
“We want a more precision-guided cancer approach. It will cost less to do therapy right and more
effectively than to do it poorly with complications.”
Dr Roy Herbst, deputy director for clinical affairs at Yale Cancer Center
“We should disseminate low-cost treatments that have come up in the last 15 years. Let’s do repurpose reverse engineering so that we can produce drugs at low cost.” Dr Rajendra Badwe, director, Tata Memorial Centre
“Easy availability of the vaccine, Cervavac, will provide a larger database for the researchers
to focus their studies on various aspects of cervical cancer prevention.” Dr Rama Joshi, principal director and head, gynae oncology and robotic surgery, Fortis Cancer Institute, Gurugram
“Personalised medicine can be involved in any type of therapy—it could be used in chemotherapy, targeted therapy and then immunotherapy.” Dr Anguraj Sadanandam, director, Centre for Global Oncology, and head, precision medicine, Institute of Cancer Research, London
“Immunotherapy seldom troubles other parts of the body. We’re in an era of targeted therapy while surgical procedures improve.” Dr Nitesh Rohatgi, senior director, medical oncology, Fortis Memorial Research Institute, Gurugram
Big Breakthroughs
CAR T-cell therapy (reengineering a patient’s own immune cells to attack cancer) has received FDA approval to treat blood cancers
Trials are on for photoimmunotherapy and it is believed to become the world’s fifth major cancer treatment after surgery, chemotherapy, radiotherapy and immunotherapy
A researcher from University of Texas has synthesised a new compound to kill a broad spectrum of hard-to-treat cancers, leaving healthy cells unscathed
At a trial in University of Michigan, oral drug Zanubrutinib was found to help most patients with marginal zone lymphoma
A study by Cancer Research, UK, and AstraZeneca UK has found that patients with advanced prostate cancer have a greater chance of survival if treated with a targeted cancer drug in addition to chemotherapy
Cancer Card
In 2020, one in six deaths globally was attributed to cancer
Breast cancer tops the list followed by lung cancer
In India, cancer cases increased at an average annual rate of 1.1-2% between 2010 and 2019
Developing countries consume only 5 percent of cytotoxic drugs; 90 percent is sold in richer nations, where 39 percent of global cancer occurs
Developing countries consume only 5 percent of cytotoxic drugs; 90 percent is sold in richer nations, where 39 percent of global cancer occurs
In 2010, cancer imposed $1.16 trillion financial burden on economies worldwide
New treatments, drugs and outlier procedures are taking the fight to the most treacherous disease in the world, even as India rolls out its first homemade cervical cancer vaccine. How close are we to a cure?