By Mark Smith, Senior Medical Manager and Hamed Khan, Associate Medical Manager

In recent years, we have witnessed the emergence of therapies with more precise pharmacological targets. Taking an example from oncology, traditional chemotherapy relies on the principle of cytotoxicity. By prevention of cell proliferation through inhibition of various phases of the cell cycle, non-targeted termination of cells was the first pharmacological method of treating cancer. Whilst various agents from this era of anticancer therapy were effective, this was a non-specific, ‘shotgun’ approach, resulting in the death of non-cancerous cells as well. For this reason, chemotherapy is well-known for its propensity to cause numerous adverse events, including alopecia, nausea, and blood dyscrasias.¹ To date, healthcare professionals must tread carefully when balancing disease control with unacceptable (and potentially fatal) toxicities associated with cytotoxic chemotherapy.

The emergence of drugs with higher selectivity or specificity to pharmacological targets has altered the landscape of cancer therapy, and modern medicine as a whole. ‘Targeted therapy’ is a broad term that often refers to the use of drugs that target specific proteins, cell surface molecules, or genes.² The concept of targeted therapy allows for improved efficacy and fewer adverse events due to higher selectivity and/or specificity. Newer molecules have advantages as targeted therapy in that their size allows them to pass easily through cell membranes to reach intended intracellular targets. Some are designed so that highly specific antigenic targeting allows for precise immune-mediated cell destruction.^3,4,5

Photo by Volodymyr Hryshchenko on Unsplash

Another term – ‘precision medicine’ – is often used to refer to medicines tailored to the individual in accordance with their genes, environment and lifestyle.⁶ This can apply at a diagnostic and predictive level, for example when selecting for cancer screening or cardiac risk assessments based on family history. Precision medicine can also apply at a therapeutic level, as seen in various cancers where biomarkers are identified to detect the presence of certain tumour cells and identify targets for anticancer therapy.

‘Personalised medicine,’ is sometimes used interchangeably with ‘precision medicine’. However, whilst many modern agents are indeed precise, with high selectivity and specificity for pharmacological targets, the question remains whether these approaches are truly personalised. The word ‘personalised’ implies that treatment is uniquely tailored to be specific to the patient, which is untrue for most targeted therapies. Interestingly, it is now possible to collect a patient’s immune cells, reprogram them to target antigens associated with cancerous cells, and then reintroduce them to the patient. These modified immune cells are then able to recognise the tumour cells and direct an immune response whereby facilitating their elimination.^7,8 This is arguably an example of personalised therapy, in that the genetically engineered cells are unique to each patient. This technology could be extended out of the oncological setting⁹, although the benefit-risk ratio would need to be considered, as such therapies are costly, time-consuming, and associated with potentially life-threatening side effects.⁸

Great strides have also been made in diagnostics via molecular testing, with whole-genome sequencing and next-generation sequencing becoming more readily available.¹⁰ These newer technologies have greater sensitivity compared with traditional single gene sequencing techniques.

Whilst whole-genome sequencing offers considerable diagnostic benefits for patients, there remain considerable barriers to its widespread implementation in clinical practice, including lack of reimbursement, limited accessibility, and inadequate standardisation of processes.¹¹ As these components improve, a personalised approach to a greater number of diseases will become more accessible. This might even extend to encompass a more holistic approach to healthcare. For example, we might be able to pre-empt if a patient is genetically more susceptible to certain side effects and tailor management, as necessary.

Precision therapy may already be here, but so too are the foundations of truly personalised medicine.

References

1. NICE. BNF. Cytotoxic Drugs. Available at: https://bnf.nice.org.uk/treatment-summaries/cytotoxic-drugs. Accessed November 2022
2. Cancer.net. What is targeted therapy? Available at: https://www.cancer.net/navigating-cancer-care/how-cancer-treated/personalized-and-targeted-therapies/what-targeted-therapy. Accessed November 2022
3. UptoDate. Overview of therapeutic monoclonal antibodies. Available at: https://www.uptodate.com/contents/overview-of-therapeutic-monoclonal-antibodies?search=monoclonal%20antibodies&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1#H2824611726. Accessed November 2022
4. Cancer Research UK. Monoclonal antibodies. Available at: https://www.cancerresearchuk.org/about-cancer/cancer-in-general/treatment/immunotherapy/types/monoclonal-antibodies. Accessed November 2022
5. AstraZeneca. Small Molecules. Available at: https://www.astrazeneca.com/r-d/next-generation-therapeutics/small-molecule.html. Accessed November 2022
6. US FDA. Precision Medicine. Available at: https://www.fda.gov/medical-devices/in-vitro-diagnostics/precision-medicine. Accessed November 2022
7. Marshall CR, et al. Genome Med. 2020;27:48.
8. ESMO Daily Reporter. CAR-T-cell therapy. Available at: https://dailyreporter.esmo.org/esmo-congress-2021/opinions/car-t-cell-therapy-the-ultimate-personalised-treatment. Accessed November 2022
9. Qin VM, et al. Cancers (Basel). 2021;13:404
10. Petersen BS, et al. BMC Genet. 2017;18:14
11. Panell M, et al. JCO Precis Oncol. 2019;3:1–9