Cancer patients often have to undergo rigorous, exhausting treatments and drug regimes, without achieving the improvements or remission that they seek. This is because certain therapies only work on a particular subset of cancers, based on the specific genetic mutations that the cells contain – if the cancer does not contain such mutations, the drug may be pointless. Moreover, patients who lack the mutation targeted by a drug will not only fail to benefit, but can actually be harmed by inappropriate targeted therapies. Therefore, it is essential that cancer treatments are tailored to each patient’s cancer, to save not only NHS money, but personal suffering too.
In the UK (and worldwide), there are many tissue biobanks that contain tumour samples for research purposes, such as the Manchester Cancer Research Centre Biobank which brings together organised tissue sample collection across four NHS Trusts under one centralised framework. Biobanks provide an essential service to scientists seeking to perform research on tumour samples to discover new genetic variants or ‘biomarkers’ that could serve as targets for new cancer therapies. In 2013, Genomics England was established to deliver the 100,000 Genomes Project, which aimed to sequence 100,000 whole genomes from NHS patients with rare diseases and common cancers. Tumour data from this project has been used for pan-cancer genome analysis, which looks at the complex patterns of genetic changes specific to different tumour types.
In cancer, tumours accumulate genetic mutations as the cancerous cells divide, grow and, in some instances, spread to other parts of the body (metastasise). The resulting tumour cells, although all derived from the patient’s own body cells, may have a very different genetic profile to the parent cells that they originated from. Indeed, as a result of the random process of mutation, the cells of the same cancer could all be different, something called ‘tumour heterogeneity’. A study by Jones et al. in 2015 strongly suggests that cancer tumour genomes should be compared to genomes from noncancerous tissue from the patient so doctors can be sure any mutations found are unique to the cancer. Moreover, when sequenced, not only do the cells in a tumour have multiple genetic changes compared to the patient’s normal body tissue, but tumours of different organ or tissue types also differ genetically from one another – each has its own genetic ‘fingerprint’ and unique pattern of biomarkers. Cancer of the breast, for instance, will have a specific suite of genetic mutations, such as in the well-known BRCA1 and BRCA2 genes, whilst there are different mutations that are characteristic of bowel cancer, such as in the APC gene.
Identifying the primary cancer
Significantly, as each tumour type has its own genetic profile, it is now possible to tell whether a tumour in a particular part of the body is a primary cancer of that tissue/organ or whether it has metastatised from elsewhere. This builds on traditional oncological investigative procedures. For instance, in 2010 a woman with primary colonic adenocarcinoma discovered a mass in her breast, which upon having a biopsy did not appear colonic in origin (and colon metastases are extremely rare), but after immunohistochemical stains it was eventually revealed that the breast tumour was indeed a colon cancer. Genetic sequencing of the tumour would likely have yielded a much prompter accurate diagnosis. This knowledge of what type of cancer the tumour really is means that drugs to combat it can be prescribed more accurately – and could give a more positive treatment outcome – which would not have been known unless the tumour DNA had been sequenced. Therefore, genetic profiling of a patient’s tumour is extremely important to ensure they receive the correct treatment.
Precision medicine and the impact on the patient
This all forms the basis of what is known as precision medicine. Precision medicine is ‘an approach to medical care in which disease prevention, diagnosis and treatment are tailored to the genes, proteins and other substances in the patient’s body’. The concept of precision medicine isn’t new, but recent technological advances have meant that this area of research has progressed tremendously in the last decade. Using next generation genetic sequencing technologies, researchers have discovered that two people with the same type of cancer may not have the same mutations, which will affect how successful the cancer treatment will be. As researchers learn more about the DNA changes that drive cancer, they are better able to design promising treatments – usually small-molecule drugs or monoclonal antibodies – that target these genetic regions and proteins. Intermountain Healthcare in the US has been using the power of new genomic technology to conduct research to advance precision medicine, such as looking at the role of tumour heterogeneity and genetic evolution in cancer. At present, genomic analysis isn’t routinely carried out on all cancer tumours in the UK, but as the technology becomes more available and less expensive, it is likely that it will be employed more by clinicians. Promisingly, studies have shown that precision medicine significantly improves survival for patients with advanced cancer when compared to control patients who received conventional chemotherapy, without the increasing associated costs.
From a patient’s perspective, it is not hard to see how precision cancer medicine will be of huge benefit. Tumour genetic profiling tells you the drugs the patient is most likely to be responsive to out of multiple possible treatments. Precision medicine saves the sufferer unnecessary pain, time, emotional energy and false hopes. For patients with advanced or metastatic cancer, which can be extremely debilitating, the genomics-based approach appears to be a more viable, and perhaps superior, option compared to standard investigations and treatments. It is, however, important to consider any potential risks to the patient of targeted therapies that are based on genetic profiling. Since the patient’s tumour is genetically sequenced to find targets for treatment, there is a slight risk to the privacy of personal information – genetic information from the patient’s health record may be obtained by people outside of the medical team, such as insurance companies, so it is very important that laws are in place to protect such data from potentially being misused.
Precision medicine is ultimately about matching the right drugs to the right patients. Genetic profiling of tumours reveals targeted therapy options that are most likely to be effective against a patient’s specific cancer. All cancers are genetically unique as a result of the mutations they accumulate. Whether genetic profiling is used to determine the true origin of a tumour (perhaps a primary cancer that has metastasised to a completely different organ) or to reveal how one person’s breast cancer (for instance) is different to next persons, this technique allows for much more personalised treatment options than are conventional. As precision medicine is geared to the uniqueness of a patient’s own DNA profile, clinicians can create more promising treatments matched to each individual than ever before, offering hope to people in their darkest hours.
1. Gagan, J., Van Allen, E.M. ‘Next-generation sequencing to guide cancer therapy’. Genome Medicine, 2015; 7(80). https://doi.org/10.1186/s13073-015-0203-x
2. Manchester Cancer Research Centre. (updated 2021) ‘About the MCRC Biobank’. [online] Available at: https://www.mcrc.manchester.ac.uk/research/mcrc-biobank/about-the-mcrc-biobank/
3. Genomics England. (updated 2021) ‘About Genomics England’. [online] Available at: https://www.genomicsengland.co.uk/about-genomics-england/
4. Shackelford, R. et al. ‘Primary Colorectal Adenocarcinoma Metastatic to the Breast: Case Report and Review of Nineteen Cases’. Case Reports in Medicine, 2011(738413). https://doi.org/10.1155/2011/738413
5. National Cancer Institute. (updated 2021) ‘Biomarker testing for cancer treatment’. [online] Available at: https://www.cancer.gov/about-cancer
6. Intermountain Healthcare. (updated 2021) ‘Precision Genomics’. [online] Available at: https://intermountainhealthcare.org/services/genomics/
7. Nadauld, L. et al. ‘Precision medicine to improve survival without increasing costs in advanced cancer patients’. Journal of Clinical Oncology, 2015; 33(15).