Simple Summary
Cancer care is becoming more personalised due to advances in molecular testing. In the past, tumours were diagnosed mainly by examining tissue under a microscope. Today, new technologies allow clinicians to study cancer in detail by analysing genes, gene activity, proteins, and the biological processes that support cancer cell survival. When this molecular information is combined with routine pathology, it provides a clearer understanding of why tumours behave differently and why patients respond differently to treatment. Large research studies have shown that this integrated approach can help clinicians better classify cancers, choose more effective therapies, and understand why some treatments stop working overtime. Although challenges remain in standardising tests and interpreting complex data, integrated diagnostic approaches represent an important step toward more precise and personalised cancer care. This review highlights the role of combining multiple molecular tests in transforming cancer diagnosis and treatment with the aim of improving patient outcomes.
Abstract
Recent advances in molecular pathology, driven by integrated and comprehensive diagnostic approaches, have significantly advanced precision oncology. By leveraging multiomics technologies, molecular pathology enables the simultaneous assessment of genomic alterations, transcriptomic profiles, proteomic activity, and metabolic states integrated with conventional pathological evaluation to better explain tumour biology and behaviour. Large-scale international consortia, including The Cancer Genome Atlas (TCGA) and the Clinical Proteomic Tumour Analysis Consortium (CPTAC) have systematically demonstrated the value of harmonised multiomics analyses in defining tumour subtypes, uncovering functional dependencies, and generating clinically actionable insights. Evidence from coordinated precision oncology initiatives, such as the National Cancer Institute—Molecular Analysis for Therapy Choice (NCI-MATCH) trial further indicates that treatment strategies guided by molecular pathology profiling are associated with improved clinical outcomes, including progression-free survival in molecularly selected patient populations. Consequently, molecularly stratified treatment approaches are increasingly required in routine clinical practice to enable targeted therapies for selected tumour entities. Integration of molecular data with functional and clinical outcomes has further facilitated the detection of emerging mechanisms of therapeutic resistance and heterogeneous treatment responses. Importantly, studies have shown that reliance on genomic analysis alone is insufficient to achieve optimal targeted therapy, underscoring the need for multi-layered molecular interrogation. This review highlights the biological and clinical relevance of multiomics integration, emphasising its critical role in comprehensive morpho-molecular tumour assessment and functional analyses while providing clinicians with a practical framework for interpreting integrated molecular diagnostics and addressing the methodological and translational challenges that must be overcome to enable broader implementation of precision oncology in routine practice.