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Creating personalised, highly effective cure for cancer, using genetics and genomics

Knowing you All that is needed to fight cancer
Tuesday, March 27, 2018 - 17:57

 

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 1,00,000 persons, over 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.

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Medical science has had one goal throughout its lifetime. And this goal will continue to be the primary motivation for advancing medical science. That is: what makes a disease? What causes it, what changes does the disease have on the human body, and how do we cure it?

Be it in the identification of the smallpox virus and the world’s first vaccine in 1798, developed by Edward Jenner, or the discovery of penicillin by Alexander Fleming in 1928.

In the last 50 years, we have understood more about the human body, and more about the building blocks that make up life. We now know about the DNA, and what it means to each cell and each organism. This discovery of the DNA, in 1953, gave birth to the field of Genetics.

Today, we are at a point in which genetics is allowing us to cross one of the biggest obstacles: cancer. Genetics and Genomics is also allowing doctors and scientists to create “personalized” medicines for cancer cure.

For Dr. T Raja, Senior Oncologist at Apollo Hospitals in Chennai, “this is very exciting!”

Personalized medicine is defined as “a form of medicine that uses information about a person’s genes, proteins, and environment to prevent, diagnose, and treat disease.” In cancer therapy, that involves understanding more about the specific cancer, and how it is formed, in order to treat it.

The Apollo Cancer Hospital, established 20 years ago, is one of the first corporate hospital specifically to treat cancer. As a senior oncologist in the hospital, Dr. Raja has been through the developments in cancer care.

He says that the convention in cancer diagnostics, in the last 100 years, has remained more or less the same.

A cancer is diagnosed using biopsy and pathology. Over the years pathology has improved and refined, with better techniques allowing doctors to be very, very precise about the diagnosis.

Doctors are now able to say exactly “what cell this cancer belongs to, how does it look, what is the grade, what is the cohesion, what are the surface characteristics it displays,” according to Dr. Raja. This is pathology, based on which treatment decisions are made.

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For instance, we can say that the cancer of the lung - which describes the organ it forms in. We can then further add that it is a small-cell lung carcinoma, which allows the doctor to figure out the best possible treatment option.

But, we are now at a quantum jump in diagnosis.

Doctors at Apollo, and other centres and institutions around the world, are trying to understand the genetic and genomic make-up of the cancer cell. The questions they ask: does the cancer cell have any real, demonstrable difference from the normal cell? How does that explain why the cancer cell has occurred, why it is growing, how it is behaving? Can we use this knowledge for any treatment end? Can we leverage this understanding of the cancer cell to kill it, and cure the patient.

This involves understanding the total cell architecture. Diving into the cell into the nucleus and DNA, to see what it can tell us, and see and understand the things DNA produces, “and what it can meaningfully tell us about cancer.” The DNA is an endless message chain. We can try to unfold it and read the messages, and in so doing see how to stop the cancer.

This approach to cancer care was first successfully demonstrated about 10 years ago, for a type of cancer called Chronic Myeloid Leukemia.

By specifically targeting a gene produced by the cancer-causing cells, doctors were able to not only cure the patient, but also ensure better long-term results and survival.

The results are “qualitatively and quantitatively better” says Dr. Raja. “Once we identified a targeted drug, we could see the disease melt away and previously untreatable disease has been cured for the long-term.”

 Since then, scientists and doctors have made further progress, and are now able to identify the genetic make-up of over 100 different kinds of tumours. The more we study, and the more precisely we are able to identify that one big change in the DNA of the cancer cell, the easier it is to develop drugs to stop the cells from growing unchecked, and easier to cure the disease.

But, there is a warning.

Dr. Raja describes it as Level 1 in a video game. We’ve successfully identified the overall genetic make-up and are able to isolate that one big, most common change in the cancer cell, and so we arrived at the end of the level. Level 2 begins. Now we have newer challenges and newer complexities, and newer problems to solve.

We may not be able to identify every change, in every type of cancer. This is because the genes and the information they contain, is elusive. There are important materials and messages in products of the DNA, and in the proteins of the DNA. Clearly identifying these messages is now very difficult, there could be slips. But this is a fast-evolving field, and these could unlock further understanding of cancer, and how to cure it.

Study of the proteins of the DNA is known as Proteomics.

Genomics and Proteomics: the new frontiers for oncology

“In 2000, we knew that one or two tumours were clearly attributable to these genetic changes, but now I can say that 100 different, fully defined genetic changes have been identified for tumours.” Doctors have been able to identify the change that drives the disease - the driver mutation, its dependent mutation, and how the tumour develops an “addiction” to these changes - known as onco addiction. And they have been trying to shut down the growth.

These advances mean that doctors - when they describe a cancer for purposes of diagnosis and cure, can be more specific. As we saw earlier, we can describe a cancer based on its organ and its type of pathology.

Now, doctors can add information about the genetic expression of that cancer. In the lung cancer example, they can now say it is an adenocarcinoma that is expressing a epidermal growth factor receptor or EGFR. This is a huge benefit. Adenocarcinoma - a kind of lung cancer, has been difficult to cure till recently, with long term prognosis for patients being very low. But doctors have been able to identify that at least 10-20% of such patients express the EGFR, causing cells to divide and replicate endlessly. By targeting the EGFR, doctors have been able to cure the cancer much better, with better long-term results.

“The cancer now has to be identified and introduced as organ, its pathology, and genetic makeup, and how far the disease has spread. So, treatment is immediately focused on genetic make-up.” This is personalised medication. This is a level of highly involved, highly focused medical care, that understands the disease, what causes it, and how to solve it. This is the newest frontiers of the system Jenner, Flemming, and other scientists and doctors first began.

Dr. Raja also says they are now able to find some interesting similarities between cancers in two widely different organs. For instance, there may be some similarities in the cancer of the head and neck, and cancer of the lung. So, doctors need to ask, and are asking, “How can both head and neck, and lung cancer express something similar? These are surprises! So, we chase through the embryology to find the reasons.”

The thrust of genetics, genomics and proteomics is to be more specific, more targeted. In order to achieve the most important goal in medicine: survival. Not just survival, but long-term disease-free survival. With genetics and genomics, cancer cure itself is moving from a general therapy, to more targeted therapy that will translate into fewer side effects, and better quality of life overall post care.

At Apollo, Dr. Raja and the other oncologist look forward to a time, in the near future, where cancer treatment is as simple as taking a blood test and taking pills for it. As Dr. Raja says, “anybody who is diagnosed with cancer, will just need to do a blood test and cancer will be identified there, its mechanism of origin, drive, growth will then be targeted. Big surgeries, radiation, chemotherapy will be redundant. Surgeries will be more and more refined, more keyhole. Mainly to acquire tissue for tests.” Some researchers have already begun exploring this idea.

 

This article has been produced by TNM Marquee in association with Apollo Hospitals.