In cancer, diagnoses are done largely by looking through the microscope at the appearance of cancer cells and, often, the organ the cancer comes from offers the most important way of making the diagnosis. But, over the past couple of decades, doctors and researchers have realised that a much better way to diagnose cancer is by the molecular abnormalities that distinguish cancer cells from normal ones; these abnormalities are often changes in the DNA sequence in the genome of the cancer cells.
Cancer is a disease of the genome. Each cell within our body contains all of the genetic code required for human life and development. This genetic code is composed of over three billion DNA molecules, joined together into 46 long strings known as chromosomes. Collectively, the DNA that makes up all 46 chromosomes is known as the genome.
Every time a cell divides, it makes two copies of its DNA that are passed on to its daughter cells. But, occasionally, errors are made while copying the DNA, resulting in mutations in the daughter cells. The great majority of mutations are harmless, but some can develop into a tumour.
Cancer genomics is the study of these mutations. For example, 12 years ago lung cancer was classified as either small cell or non-small cell. Today, it is identified by nearly 30 genomic mutations or changes. Identifying specific mutations in patients marks a radical shift from a one-size-fits-all treatment towards more personalised therapy.
Precision medicine
Precision medicine’s central principle centres on the ability to identify personal gene characteristics and match them to specific treatment options. It is an emerging approach in cancer treatment and prevention.
DNA changes, or patterns of changes, can now be used to predict which drugs might be effective, as well as to decide in which patients to use more aggressive therapy. The genomic information can also be now used to predict which patients may have a toxic response to some drugs. Furthermore, it has become clear that some cancers arising in different organs (for example, breast or prostate) can have the same kinds of genomic changes, meaning the same kind of therapy can be equally effective for these patients. This is important as it means there are existing drugs used for patients with breast cancer that could also be used for patients with prostate cancer.
“Fundamentally, I am alive because of genomic testing,” says Dr Sharon Stanley, a cancer patient and an osteopathic physician. “I had uterine cancer, an advanced stage, very aggressive type of sarcoma. I went through a chemotherapeutic regimen, but I did not go into a full remission. Because I had mutations [associated with lung cancer], it didn’t matter if I had uterine cancer; I could get on to Keytruda (a drug), which was approved for lung cancer, and to which I responded very well. If this hadn’t happened, the likelihood of me being alive was under 10 per cent. But now, I’m headed into what appears to be a full remission and even better news is that it is an opportunity for individual treatments based on these markers as opposed to the classic treatment of tumours based on tissue type.
Genomic testing
All patients with a diagnosis of cancer should at some point in their clinical journey go for testing to identify some of the genomic molecular changes that contribute to their disease. Deep understanding of these molecular changes have led to a transformation in cancer care. The testing can be done on tissue after a biopsy of the patient’s tumour or other samples that may have tumour DNA as well, such as in the blood or sometimes in the urine. Detecting these changes are likely to play a critical role in helping the physician choose between several treatment options.
Another unique story is that of Prof William Burhans, a senior cancer scientist at Roswell Park Cancer Institute in New York. Dr Burhans was diagnosed in 2013 with an aggressive prostate adenocarcinoma and went through the usual treatment. But because of the aggressive nature of the tumour, the benefits of the treatment lasted only a short time. He had a family history of cancer and was tested for germ line (sex cells) mutation. The results determined that he had a mutation in the BRCA2 gene, which is associated more frequently with ovarian and breast cancer, and with prostate cancer in some cases. He began treatment with a drug called olaparib, which was approved for patients with ovarian cancer who also had these mutations. “I was told at the beginning of my treatment that I probably had no more than a few months left,” said Burhans. “But here I am now, healthier than otherwise.”
How affordable is genetic and genomic sequencing?
The human genome is made of more than six billion letters, and each person has a unique configuration of As, Cs, Gs, and Ts―the molecular building blocks that make up DNA. Determining the sequence of all those letters used to take vast amounts of money, time and effort. The Human Genome Project took 13 years and thousands of researchers. The final cost: $2.7 billion.
Sequencing has led to genetically targeted drugs, blood tests that can detect cancer early, and diagnoses for people with rare diseases. In research labs, the technology has become essential, but it is still not ubiquitous in medicine. That is in part because of the price. While it costs around $600 for scientists to perform sequencing, clinical interpretation and genetic counselling can drive the price to a few thousand dollars for patients, and insurance doesn’t always cover it. However, the market is competitive with companies vying to launch testing with reduced prices. In the past decade, the cost of genomic testing has come down from about $100/Gigabase (unit of measurement used to help designate the length of DNA) to $10/GigaBase, and are further set to reduce to below $5/GigaBase in the near future.
In India, genomic testing has grown from very little in 2015 to the order of a hundred thousand clinical tests today. The project to bring affordable personal gene mapping to India’s 1.4 billion people will potentially create a treasure trove of biological data that can aid drug development and disease prevention.
Preventive wellness
A decade or so ago, genomic testing got attention when Hollywood star Angelina Jolie went on to describe how her doctors estimated that she had an 87 per cent risk of breast cancer and a 50 per cent risk of ovarian cancer on account of a genomic variant in a gene called BRCA1. She underwent preventive surgery, as a result of which her risk reduced to that of the average woman of her age.
The dramatic cost reduction has fuelled the increasing adoption of these tests for preventive wellness. A recent study published by Mayo Clinic Proceedings indicates that nearly one in eight people who underwent predictive genomic testing found that they had a genetic risk for a health condition and may be able to manage it better with preventive care. Rising adoption of healthier lifestyles and increasing awareness of genomics are expected to drive demand for predictive genomic testing.
The number of people getting DNA reports has been doubling, roughly, every year since 2010. The DNA repositories are now so big that they are enabling surprising new applications.
Even then, some think we are spending too much time searching under the lamplight shed by genetic tools. As Pulitzer Prize-winning cancer doctor Siddhartha Mukherjee wrote: “Perhaps we had been seduced by the technology of gene sequencing―by the sheer wizardry of being able to look at a cancer’s genetic core.”
Priya Menon produces and hosts CureTalks, an internet talk show on health care. She works as vice president, TrialX, a clinical trial solutions company headquartered in New York.