Cancer has been this century’s most challenging health issue, and the scientific world, even after decades of untiring search, is still groping in the dark as far as resolving this enigma of a disease is concerned. Recent molecular studies on cancer cells, made possible by advancing research and technologies, has now made it clear that wide variations within the one broad generic nomenclature of cancer makes the search for a cure all the more difficult. According to Dr Madhavan V Pillai MD, a physician specialised in Internal Medicine, Hematology and Medical Oncology and certified by American Board of Internal Medicine, the biggest challenge that the scientific world is facing at present is this variation. Each type of cancer — like breast cancer, lung cancer, brain cancer, bladder cancer etc. — are no longer considered a single disease, but a combination of very different diseases, mechanisms, prognosis, responses to treatment and patient outcomes.
Dr Pillai, a Clinical Professor of Oncology at the Sidney Kimmel Medical College of Thomas Jefferson University and President & CEO of International Network for Cancer Treatment and Research (INCTR- USA), is also a Fellow of the American College of Physicians (FACP) and Senior Advisor to Global Virus Network (GVN). A graduate and postgraduate in Internal Medicine from Thiruvananthapuram Medical College, Dr Pillai received specialty training in Hematology at Auckland University Hospital, New Zealand and later in Hematology and Medical Oncology at the Medical College of Virginia. Excerpts of his Straight Talk with Editor
What are the most recent developments that cancer researchers could bring to the understanding of cancer and what are the latest options available in the treatments, especially in a country like India?
I think almost all the resources available in the western world is right now available in India. In order to explain the context well, I can say the current treatments for cancer is conventionally divided into four major categories, including surgery, radiation, chemotherapy and the new targeted therapies. For example, 25 years ago, when we see a case of breast cancer, we knew that the patient needs to be operated and some may need radiation, and some are likely to put on chemotherapy. But this is no longer the case now. As per the current understanding of the disease, breast cancer is no longer a single disease. It is a conglomeration of 20 to 30 diseases depending on the trigger, the genotypes, the expression etc., and this analysis came
from the molecular study of the cancer cells. And if one doesn’t know this, they are actually comparing apples to oranges.
That’s the challenge. When you are dealing with these multiplicities, you should know the fundamental issue with the disease, which is damage to the DNA. Once the DNA is damaged, it loses its competence to take orders from the central system and thus loses its control on proliferation. So, what happens in case of cancer is that the cells acquire a capacity to start dividing and proliferating on their own and it becomes uncontrollable as they don’t obey any rules. As a result, the cluster cells lose the capacity to destroy them and in turn invite the blood vessels to come to such locations of damaged cell accumulations (tumours) and supply nutrition. This also leads to metastasis or the spread of cancer cells to other parts of the body. So, the success of a treatment would always depend on the depth of understanding of the exact nature of the disease. We have made many technological advancements in getting to know at least some of these variations. There are now new treatment options which can play key roles in destroying the damaged cells, blocking the supply of blood, encouraging programmed cell death without damaging the cells in surrounding areas and so on. [The right strategy] needs to be chosen according to this understanding.
Although there were several drugs, including biologicals, approved for cancer treatment in the recent times, the success rate for most of them are limited to 50 to 60 percent. How do we tackle the disease in such a situation?
This is absolutely right, and it is another big challenge. That is the reason for trying out combination treatments, depending on the understanding of the nature of the disease. As you know, we have one set of drugs that destroys the cancer cells blindly and there is another group of drugs which blocks the blood supply to the tumour colony. So, we use chemotherapy to destroy the damaged cell colonies and we use the vascular endothelial growth factor receptor blockers to stop the blood supply to the area. In addition, we have a set of drugs that restore apoptosis — a programmed sequence of events that leads to the elimination of cells without releasing harmful substances into the surrounding area, which plays a crucial role in developing and maintaining the health of the body by eliminating old cells, unnecessary cells, and unhealthy cells. There are also new drugs to arrest metastasis — which helps to stop the spread of cancer cells to other locations.
How successful is targeted therapy in your experience?
In the sense of survival rate, yes targeted therapy has been very successful. But it hasn’t cured any cancer so far. Evidence shows that targeted therapy using the drug imatinib has helped the prolonged survival of patients in case of chronic myeloid leukaemia. It is proven that when this medication was given as first, second, third and fourth line therapy after checking the progress and the remission (measuring the symptoms, blood count and the oncogene BCR/ABL), patient survival got extended to even up to 12 years after diagnosis. But the issue of finding no cure so far is because of the resistance developed by the cancer against the medication. Recent studies have shown that resistance actually starts from the beginning and [is not developed] over a period of time. So, there is research going on to learn the mechanisms of resistance and how to avoid this. Experiments, after identifying the responsible clones (for sensitivity and resistance respectively), have shown promising results for cure. But it doesn’t mean anything unless it is clinically proven.
What are the latest or the most superior therapies that are likely to hit mainstream treatment?
The latest weapon in our armamentarium is the immune checkpoint inhibitor, which is a type of immunotherapy. As you know, our body has two types of lymphocytes: B-lymphocytes and T-lymphocytes. These lymphocytes have a key role in creating resistance against many diseases, mainly infections. But now, we have come to know that they are very active in cancer as well. So, T-lymphocytes have a built-in system by which they go and attack intruders like viruses, fungi etc., as they get the signal that there is an intruder or damage. Cancer cells have a tendency to manufacture immune checkpoints and attack the T-cells. So immune checkpoint inhibitors are targeted at blocking the proteins that stop the immune system from attacking the cancer cells. Cancer growth and progression are typically associated with immune suppression. Since cancer cells have the ability to activate different immune checkpoint pathways that harbour immunosuppressive functions, monoclonal antibodies that target such immune checkpoints provided an immense breakthrough in cancer therapies. Many immunotherapy drugs are already approved and available in the world, including India, though the cost remains the biggest concern. I know two patients with metastatic cancers under this treatment even in India and they are doing well and could extend the survival beyond the fourth year of diagnosis. But the cost is far beyond the common man’s reach. So, is it worth prescribing this? Here comes the biggest dilemma of the doctor — the moral dilemma created by limited medical resources, and the conflict between the demands of private medicine as a business and a vocation.