Precision oncology allows for targeted therapy based on a person’s molecular and genetic characteristics. We know that cancer is an extremely heterogeneous disease – both between patients and even within the cancer cells of an individual patient. Precision oncology is based on the premise that there is no “one size fits all” treatment. The future of cancer care may well be one where a patient’s genetic profile is a standard part of oncology care, driving how we approach the detection, diagnosis, treatment, and outcomes of cancer patients around the world.

The ultimate goal of precision oncology is to improve patient outcomes. “Traditional” cancer therapies like chemotherapy is cytotoxic to most cells, so it can damage healthy cells in addition to killing cancer cells. While chemotherapy can be very effective and is a mainstay of cancer treatment for many patients, it also comes with the potential for many side effects.

Precision oncology allows for targeted therapy, which hones in on a specific genetic biomarker. By doing this, targeted therapies can block cancer cells with that genetic biomarker from dividing and growing – sparing healthy cells, and limiting side effects. Some precision oncology treatments do not target only the origin of the tumor (e.g., breast or lung cancer cells), but any cell in the body with an oncogenic mutation (and thus, has the potential to be cancerous). Studies have also been performed to discover targets that predict the effectiveness of chemotherapy and radiation therapy.

Cancer biomarkers include structural changes within the genome, abnormal features of gene products, or biochemical effects of the tumour. Cancer biomarkers can include:

• Proteins
• Gene mutations
• Gene rearrangements
• Extra copies of genes
• Missing genes
• RNA
• Signaling molecules, such as hormones

Some cancer biomarkers can be used to predict how aggressively cancer will grow, and are therefore useful for assessing prognosis. However, one may argue that the most promising use of biomarkers is to identify which therapies a particular patient’s cancer may or may not respond to, thereby optimizing their treatment plan.

After decades of research, several cancer biomarkers across different cancer types have been identified, with more being identified as research continues. Commonly known genetic biomarkers include EGFR, ALK, MET, ROS1, NTRK, HER2, KIT, BRAF and BRCA1/BRCA2. Mutations in these genes have been validated as powerful predictive biomarkers in the management of diverse solid tumours such as non-small cell lung cancer (NSCLC), gastric cancer, gastrointestinal stromal tumours, melanoma, breast cancer and ovarian cancer. Moreover, effective cancer therapies (referred to as “targeted therapy” or “biologic therapy”) have been developed to target these specific biomarkers.

Despite many breakthroughs in recent years, a precision oncology approach to treatment is not yet part of routine care for most patients. The presence of actionable genetic insights, or biomarkers, is not known for all cancer types. This is what makes continued translational and clinical research in precision oncology critical.

Although targeted therapies have shown much promise, implementation across the broad landscape of oncology presents challenges. These include:

• Need for deeper understanding of the functional consequences of variant alleles
• Clinical research and practice models that are more patient-centered and account for the complexity of individual patient tumours
• Need for greater enrollment of appropriate patients in clinical trials

The influence of new technologies also holds much promise. For example, the CRISPR/Cas system and cryo-electron microscopy (cryo-EM), whose discoverers were awarded the 2020 Nobel Prize in Chemistry, will broaden and sharpen our ability to identify novel therapeutic targets for precision oncology. CRISPR/Cas technology enables the controlled exchange, insertion and deletion of DNA sequences (gene editing), and can easily generate animal models that mimic the mutational status of patients.

The importance of precision medicine research is underscored by the large-scale support of the Canadian government. In 2018, the Government of Canada announced two new major investments in genomics research totalling $255 million from federal and provincial governments, as well as research institutions and private sector partners. Cancer treatment, in particular, stands to highly benefit from personalized therapies, since extensive variability between tumours presents a need to target each case in a personalized manner.