The Evolution of Cancer Treatment: From Histology to Molecular Medicine
Over the past few decades, oncology, and medicine in general, has begun to emphasize precision medicine and biology-driven strategies, increasing cancer survival rates and quality of life. More specifically, there has been a transition from a histological to a molecular profiling approach. In the past, cancers were classified mainly by their site and histology, creating a serious limitation: uneven responses to treatment. Recently, technological advancement has allowed genomics and epigenetics to reshape how treatments are chosen, causing modern oncology to become increasingly biomarker-driven and personalized.
Two canonical examples exemplify how cancer genomics have led to targeted therapeutics. The BCR-ABL gene, discovered in 1985 and known to be a marker for chronic myelogenous leukemia (CML), is now treated with imatinib, a selective BCR-ABL tyrosine kinase inhibitor. Prior to imatinib, management relied on interferon-based therapy or bone marrow transplantation, both associated with significant morbidity. Imatinib transformed CML into a largely manageable chronic disease, with dramatic improvements in survival and quality of life, and is widely regarded as a proof-of-concept for targeted cancer therapy.1 Another canonical example is HER2 amplification in breast cancer. Approximately 15–20% of breast cancers overexpress the HER2 receptor, which is associated with aggressive disease and poor prognosis. The development of trastuzumab, a monoclonal antibody targeting HER2, significantly improved outcomes when added to chemotherapy in both metastatic and early-stage disease. This marked one of the first successful applications of monoclonal antibody therapy in solid tumors and demonstrated how molecular subtyping could guide treatment selection.2 HER2-targeted therapy has since expanded to include additional agents, reinforcing the principle that sustained inhibition of a defined oncogenic pathway can yield durable clinical benefit. The development of imatinib and trastuzumab are two examples of the recent shift away from empiric chemotherapy and towards a molecular and genomic approach to oncology.
Beyond the development of targeted agents, cancer genomics has fundamentally reshaped how patients are stratified and how treatments are selected. Not all patients derive benefit from the same therapies, even within a single histologic cancer type. Predictive biomarkers enable clinicians to identify patients most likely to respond to specific treatments while sparing others from ineffective therapy and unnecessary toxicity. For example, microsatellite instability status and tumour mutational burden have emerged as clinically relevant biomarkers that inform the use of immunotherapy across multiple cancer types. Similarly, the increasing use of companion diagnostics ensures that targeted agents are prescribed only when their corresponding molecular targets are present. A genomics-guided approach represents a shift from uniform treatment algorithms toward more individualized care, improving therapeutic efficacy and safety. Aligning treatment choice with tumor biology has allowed genomic stratification to become central in modern oncology practice and refine clinical decision-making.
In addition to genetic alterations, epigenetic dysregulation has emerged as a key hallmark of cancer, contributing to abnormal gene expression without changes to the underlying DNA sequence. Unlike genetic mutations, epigenetic modifications may be reversible, creating therapeutic opportunities, leading to the development of epigenetic therapies such as DNA methyltransferase inhibitors and histone deacetylase inhibitors, which are used primarily in haematological malignancies including myelodysplastic syndromes and certain lymphomas. While their activity as single agents is modest in some settings, epigenetic therapies are increasingly being prescribed alongside chemotherapy, targeted therapy, and immunotherapy to create a combination therapy. Epigenetic targeted therapies, an emerging and complementary dimension of modern cancer therapy, aim to enhance treatment response and overcome resistance.
Oncology is now inseparable from molecular medicine. An understanding of cancer genomics, epigenetics, and biomarker-driven treatment selection is becoming essential to clinical practice. As the field continues to evolve, genomic research will drive changes in the oncological landscape.
References
1. Druker BJ, Talpaz M, Resta DJ, et al. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001;344(14):1031–1037.
2. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V, Bajamonde A. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med. 2001;344(11):783–792.
