Medical science has one goal it holds above everything else: cure disease with as little effort as possible.
This goal has been the driving force in the discovery of anti-biotics that cure infections, it has been behind the development of pain killers, beta blockers, vaccine shots for TB, small pox, polio and the like. Scientists and medical professionals broke through the disease barrier and, with a small pill, ensured a longer, happier life for all of us.
Until a few years ago, cancer - one of the deadliest diseases in the world - had no single cure. Most medical procedures for cancer involved chemotherapy and radiation, which not only killed cancer cells, but also killed healthy, vital cells in the human body. Chemotherapy and radiation together have a heavier impact on the patient, creating long-term side effects which could sometimes be fatal. More importantly, the quality of life of the patient is drastically reduced.
But today, Dr. Sankar Srinivasan, a senior Medical Oncologist at Apollo Hospitals, is able to offer his patients a better choice. Next Generation Targeted Therapies.
“Basically, targeted therapy comes from an idea: can we attack the cancer directly, with minimal collateral damage? When we look at cancer cells, they are abnormal, they are different to normal healthy cells. That has been a problem however, when we try to kill the cancer cells, some normal cells are also destroyed in the process. The side effects are huge, and our ability to increase dosage is affected. The stronger the dose, the more the side effects. That’s why, targeted therapy,” says Dr. Sankar.
The development of medical science, especially in cancer research, has brought rich dividends, and Dr. Sankar and other medical oncologists around the world, are at a stage where they can treat cancer with just a pill.
Next Generation Targeted Therapy involves understanding the cancer, it’s drivers, the underlying protein structure and cell structure of each cancer, and manipulating it to reduce the cancer’s growth and thus cure the disease.
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Evolution of Targeted Therapy
Targeted therapy has been around for a while as a discipline under cancer care, but it is now increasingly used for multiple cancers and for a better overall patient experience. Dr. Sankar Srinivasan says that the first cancers to be treated using targeted therapy was breast. “We treated it with hormones, blocking the estrogen,” says Dr. Sankar.
The effect of hormones - especially estrogen and progesterone - on breast cancer, was in fact identified much earlier. In 1874, Thomas Beatson of Edinburgh discovered that removal of the ovaries in rabbits impacted their ability to secrete milk, and later used this knowledge to treat breast cancer patients. Although estrogen and other hormones were not yet discovered, Thomas Beaston correctly identified the ovaries as having an effect on breast cancer. Later, urologist Charles Huggins discovered that removal of the testicles of male patients with prostate cancer dramatically regressed, and controlled that cancer.
While early methods of “targeted therapies” involved surgery, development in medical science today, especially the understanding of cancer genetics and proteomics (the study of proteins formed inside the cell) has helped improve the ability of Dr. Sankar to diagnose exactly the right type of cancer and the right type of drug to control and treat it.
“Off late, since the 90s and 2000s, we are getting more and more specific. Take Chronic Myeloid Leukemia (CML) - which has the characteristic ‘Philadelphia Chromosome’ - it’s a characteristic genetic abnormality. So in the late 90s, a medicine called Imatinib was identified, which essentially takes care of the Philadelhphia chromosome, and we are able to treat this chronic leukemia with a tablet, with minimal side effect.”
In the 90s, when Dr. Sankar Srinivasan was training to specialise in cancer care, the standard treatment protocol for CML was bone marrow transplant - which had high morbidity and mortality rates. Patients with CML, who received bone marrow transplants, had a very poor survival rate. Some studies showed that only about 34% of patients survived beyond the 20 year mark. Now the standard treatment is targeted therapy using Imatinib - a simple tablet.
“80-90% of the patients do very well, have a normal life,” says Dr. Sankar.
Scientists and doctors, along with big pharmaceutical organisations, have been researching cancer for well over 100 years now. In the last few decades, research has gone into identifying and describing the cancer better - this involves identifying the organ where the cancer forms, the physical features exhibited by the cancer, and the major “driver” of the cancer - for instance, receptors for hormones such as estrogen in breast cancer.
Once doctors know what the cancer is and how it multiplies and what factors contribute to its growth, they can quickly identify a suitable drug to limit the “drivers” and prevent the cancer from metastasising - spreading to other healthy parts of the body, and eventually control and treat it with very little side effects.
“Our diagnostics and therapeutics have improved so much, that we are now able to use these kind of medications, say in lung cancer. We have small molecular targeted therapy like Erlotinib, which works in about one-third of these lung cancers, where before chemotherapy was used. Erlotinib is only an oral tablet.”
Erlotinib acts on the epidermal receptor type 1 or the epidermal growth factor receptor, that is present in many non-small cell lung cancer patients.
Similar developments in targeted therapy attack specific receptors and chromosomes that drive the cancer’s growth, and treat it.
The Burden of disease, and the need for greater research
This is particularly important because the cancer burden in India is high. A 2012 Report on Cancer by the WHO reports that there is an estimated 1.01 million new cancer cases in India - or about 94 per 100000 persons, and 980,000 cancer-related deaths. While risk factors vary from region to region in the country, some are largely common - especially in big cities. Pollution, high salt and spices in food, very little physical activity.
Other factors, including long-term smoking, exposure to certain drugs and hereditary causes, also increase the risk of developing cancer. The risk is high enough to cause the government of India and various state governments to create an integrated, extensive cancer management and control programme, perhaps one of the earliest countries in the world to do so.
The Apollo Hospitals group understood the risk early on, and was one of the first large corporate hospitals to set up a specialised cancer treatment centre - the Apollo Cancer Hospitals. Here, Oncologists such as Dr. Sankar Srinivasan are clued into the latest research and disease management procedures, and bring global best practices to India almost as soon as they are available anywhere else.
“Essentially what we are trying to do in targeted therapy is, try to find some sort of mutation within the tumour cells, or find a protein - either it is lacking, or which is produced in excess by the tumour cells - and utilise that protein or gene to attack the cancer cells, without affecting much of the normal cells.” Dr. Sankar Srinivasan says most of research is now going into this field, and will result in better patient outcomes, and better disease management overall.
However, Dr. Sankar Srinivasan offers a word of warning. Drugs and medicines developed for one type of cancer may not have a great effect on other cancers. Further, doctors have perhaps been able to identify one principle or characteristic mutation in cancer cells, and have found ways to target it. But there could be a situation where either the cancer cells develop resistance to that particular drug, or there may be further mutations and changes that do not work in the same way, and therefore the drugs are ineffective.
He gives an example of B-RAF mutation for Melanoma or skin cancer. Doctors were able to treat it using a drug called Vemurafenib. “It worked extremely well in these mutated cells,” says Dr. Sankar Srinivasan. Oncologist then tried to identify if the B-RAF mutation was present in other malignancies, such as colo-rectal cancer. While Vemurafenib seemed to have some effect, the scale and scope of such a drug was much reduced for cancers other than melanoma.
This will mean that continuous effort must be put into research and development, in order to identity more and more, and more nuanced factors that drive cancer, and develop specific drugs that act on it. Thankfully, medical researchers around the world, pharmaceutical companies, and hospitals such as Apollo, and Dr. Sankar Srinivasan specially, are working around the clock to do exactly that. With clinical trials, newer disease management protocols, site specific cancer care, and newer, more effective drugs, there is hope that this “emperor of maladies” will finally be conquered.