Personalized Medicine and Biomarkers: Applications, Challenges, and Future Directions

Introduction

The traditional “one-size-fits-all” concept is shifting towards a more customized approach in personalized or precision medicine (PM), focusing on individual patient needs.  The National Human Genome Research Institute (U.S.) defines PM as “an emerging approach to medical practice that uses an individual’s genetic profile to guide decisions for the prevention, diagnosis, and treatment of disease”. Central to PM are biomarkers, measurable indicators of pathological and physiological responses¹. This article explores the use of PM across various therapeutic areas, as well as its limitations, challenges and recent advances in clinical trial design.

Cancer

The complexity and heterogeneity of cancer make it challenging to manage, which is why PM has proven especially crucial in oncology. Biomarkers enable the identification of cancer subtypes, allowing for tailored treatment strategies. For instance, breast cancer can be classified based on the presence of biomarkers like estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), which inform treatment decisions such as the use of hormone therapy or chemotherapy. HER2-targeted therapies, including trastuzumab and pertuzumab, have improved outcomes for HER2-positive breast cancer patients¹. Similarly, in non-small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) pathway can be targeted by EGFR tyrosine kinase inhibitors (TKIs). Phase III studies have shown that first and second-generation TKIs (gefitinib, erlotinib, afatinib) are superior to chemotherapy in overall response rate and progression-free survival. Additionally, osimertinib, a third-generation TKI, has demonstrated improved survival over first-generation TKIs and is now widely regarded as the standard of care for first-line treatment².

Severe Asthma

PM is also transforming the treatment of severe asthma. Previously viewed as a single diagnosis with standardized treatment, asthma is now recognized as a heterogeneous condition with distinct phenotypes and endotypes. Most asthma cases involve type 2 (T2) inflammation, driven by cytokines like interleukin-4 and interleukin-5, as well as inflammatory cells. A few clinical biomarkers, such as immunoglobulin E (IgE) and eosinophil count, are currently available. While biomarker-based management of asthma is still somewhat limited, their use could play a critical role in enhancing the effectiveness of biological treatments. For example, omalizumab, an anti-IgE antibody, is dosed according to the patient’s age and baseline free IgE levels. Similarly, mepolizumab, an anti-IL-5 biologic, reduces exacerbations in patients with elevated eosinophil count, improving quality of life³.

Autoimmune diseases

In systemic lupus erythematosus (SLE), a chronic autoimmune inflammatory disease, advancements in PM are similarly creating new opportunities for personalised treatment. Recent breakthroughs in transcriptomics, especially single-cell RNA sequencing (scRNA-seq), have identified molecular biomarkers that may predict disease progression, outcomes, and individualised therapy. Studies have shown that changes in immune cells along with proinflammatory cytokines such as type 1 interferons, IL-18, and TNF, are linked to SLE activity⁴. These findings create opportunities for targeted treatments, like TNF-α inhibitors, which have demonstrated success in reducing inflammation and improving symptoms in other autoimmune diseases like rheumatoid arthritis⁵.

Challenges, Limitations and Clinical Trial Design

Despite its potential, PM faces challenges such as data complexity, clinical trial design and biomarker validation. Additional limitations include cost, accessibility, ethical concerns and resistance to targeted therapies¹. One common approach is the enrichment design, where only biomarker-positive patients are randomized into treatment or control arms. This design is recommended only when the biomarker perfectly predicts response to treatment, to avoid excluding biomarker-negative patients who may still benefit from the treatment. More complex designs, such as basket, umbrella, and platform trials, have emerged. However, implementing these in PM trials presents challenges, including randomisation, use of control arm and biomarker stratification⁶.

Conclusion

PM is transforming healthcare by tailoring treatments to individual genetic profiles, with promising results across various therapeutic areas. However, it presents several challenges. Despite these hurdles, innovative clinical trial methodologies can promote patient-centric research, potentially leading to the adoption of personalized medicine as a standard of care.

MEDiSTRAVA’s Clinical Trial Optimization team offers expertise to maximise clinical trial success from protocol development, through recruitment and retention, and on to translation into the real world, whilst meeting the most rigorous scientific and regulatory standards.

Citations

1. Gadade D, at al. Unlocking the power of precision medicine: exploring the role of biomarkers in cancer management. Future Journal of Pharmaceutical Sciences. 2024;10(1):5. doi:10.1186/s43094-023-00573-2
2. Ferro A, et al. The study of primary and acquired resistance to first-line osimertinib to improve the outcome of EGFR-mutated advanced Non-small cell lung cancer patients: the challenge is open for new therapeutic strategies. Crit Rev Oncol Hematol. 2024;196:104295. doi:10.1016/j.critrevonc.2024.104295
3. Chen C, et al. Personalized Medicine in Severe Asthma: From Biomarkers to Biologics. Int J Mol Sci. 2023;25(1). doi:10.3390/ijms25010182
4. Fenton K and Pedersen H. Advanced methods and novel biomarkers in autoimmune diseases ‑ a review of the recent years progress in systemic lupus erythematosus. Front Med (Lausanne). 2023;10:1183535. doi:10.3389/fmed.2023.1183535
5. Gao Y, et al. Rheumatoid arthritis: pathogenesis and therapeutic advances. MedComm (2020) 2024;5(3):e509. doi:10.1002/mco2.509
6. Superchi C, et al. Study designs for clinical trials applied to personalised medicine: a scoping review. BMJ Open. 2022;12(5):e052926. doi:10.1136/bmjopen-2021-052926