Precision Medicine: The key to improved cancer outcomes in poor-prognosis cancers?
Precision, or personalised medicine in oncology refers to treating a patient’s cancer based on the specific makeup of their cancer and not by applying a one-size-fits-all approach. This often involves using newer ‘targeted’ treatments and foregoing traditional chemotherapy approaches. As an oncologist, I have seen firsthand the difference this has made to select patients, not just with regards to their better outcomes from treatment, but also due to the improved side effects from these treatments.
Our project is focused on patients with advanced gastrointestinal cancers (including liver, stomach, oesophagus, and pancreas). Unfortunately, a large majority of the patients that present to our clinic do so at an incurable stage, and outcomes remain poor with traditional treatment pathways. We seek to examine how applying a precision medicine approach to patients with advanced gastrointestinal cancers changes the treatment plan and overall outcome. We are also particularly interested in recognising any common changes in the makeup of patients' cancers that might lead us to new potential targets for treatment.
So how do we do this? Genomic sequencing allows us to examine the makeup of the cell by ‘reading’ the DNA, which makes up our genes. Genes are essentially instructions for our bodies. By doing this we can identify if there have been any abnormal changes in the genes, also called mutations. Mutations may be responsible for the development of cancer or can drive the behaviour of cancer. If we can identify what is driving the growth of cancer, we may be able to use an existing treatment that can act on that exact change and stop the growth, or potentially develop a new treatment based on that change.
There is one problem with this approach, however. Genomic sequencing produces a lot of data. Also, not all mutations that we identify are responsible for causing cancer. What we want to do is to try and pick out patterns common to cancers, indicating this might be driving the growth of that cancer. One way of overcoming this is to examine people who have an unusual presentation of their cancer, for example at a younger age than expected or had an unexpected response to cancer treatment, either good or bad. We call these ‘extreme phenotypes’. By studying extreme phenotypes we improve the likelihood of discovering a meaningful, cancer-driving mutation that might prove useful as a target for treatment to a larger group of patients
Preliminary work on our project commenced before the Covid- 19 pandemic and it would be remiss to talk about our research study without mentioning how the pandemic has affected it. Before we can recruit our first patient, there is a necessary but lengthy process to ensure the study meets the expected ethical, data protection, and clinical standards. As the medical and indeed wider community were grappling with the frightening new reality of SARS-CoV2, time and resources were appropriately focused on clinical care.
Processes for approval in the relevant committees were lengthier (many of these committees are made up of healthcare professionals and others who are volunteering their time to participate) and as oncologists, we were focused on implementing new patterns of care and familiarising ourselves with how to treat Covid-19. Following the initial stages of the pandemic, however, the oncology community has advocated for continuing research studies and clinical trials - these are essential for providing access to new treatments to our patients and in driving forward our progress in the treatment of cancer.
There are some advantages to precision medicine during a pandemic. Many of these targeted drugs have a different way of working than traditional chemotherapies and as such have a different set of side effects. One thing we worry about with traditional chemotherapies is their ability to affect the body’s immune system and hamper its ability to fight off infection. Naturally, this is a serious concern when in the midst of a pandemic, as it may put patients at increased risk of a severe disease course from Covid-19. In many cases, these targeted treatments are not as immunosuppressive as chemotherapies.
Many, but not all, of the targeted treatments, are taken orally. This can reduce the frequency our patients attend the hospital in person, reducing the risk of contracting the virus. The other hope with a precision medicine approach, although not guaranteed, unfortunately, is that if we can offer targeted treatment, this will be more effective at treating an individual’s cancer and in turn lead to healthier patients who are more able to withstand the effects of Covid-19.
Our project run by Prof Maeve Lowery, Professor of Translational Cancer Medicine in Trinity College Dublin, will enable upper gastrointestinal cancer patients in Ireland with extreme phenotypes to have genomic sequencing of their cancer performed. We hope to tailor treatment plans for those patients based on their cancer genetic makeup and also to examine patterns within all of our patients to identify new targets for treatments. This is a pilot project, to see how feasible the approach is in a small number of patients, but we hope if successful to expand this approach to more patients across Ireland.
Author: Lynda Corrigan
Author's Note: I am a Medical Oncologist currently pursuing an MD, Doctor of Medicine, a degree in the field of oncogenomics under the auspices of Prof. Maeve Lowery. I have a keen interest in the area of oncogenomics and upper gastrointestinal cancers. My training has provided me with extensive experience in clinical research which has given me a robust understanding of the practical implications of precision medicine for oncology patients. Precision Oncology Ireland provides a unique opportunity to build partnerships, share expertise and enhance output within this exciting field, with the ultimate goal of advancing oncology diagnostics and treatments for cancer patients.