The Emerging Power of Mass Spectrometry in Oncology

Globally, the incidence of newly diagnosed cancer cases is projected to increase over the next decade.¹ Despite advancements in personalized medicine and therapeutic options, cancer diagnoses remain challenging.

Many patients are diagnosed at advanced stages (III/IV) when the disease has metastasized, resulting in poorer prognoses and clinical outcomes. Improving patient outcomes requires technological advancements that enable early detection when the disease is localized (stages I/II). However, effective screening options for many cancer types remain limited.

Novel approaches are urgently needed to improve availability and accessibility of diagnostic assays and, to that end, recent efforts in the field have shifted toward uncovering the biological pathways and molecular profiles underlying disease onset, progression, and metastasis.

Liquid biopsy, a minimally invasive blood-based technology that detects tumor-derived biomarkers, has the potential to detect cancer at earlier stages (I/II) and positively impact patient survival. Many liquid biopsy assays are under development or in the early stages of commercial availability, and are designed to detect mutations, methylation patterns, and/or fragmentation patterns in circulating tumor DNA (ctDNA) by next-generation sequencing (NGS)-based technologies.

However, limitations remain due to complexity and cost, and their performance for early-stage cancer detection remains largely unproven.

Powerful tools for oncology

A technology that offers the opportunity to rise above these limitations is mass spectrometry. MS-based omics approaches (the study of all biological molecules within an organism, grouped into subdisciplines such as proteomics, lipidomics, and metabolomics; the study of all proteins, lipids, and metabolites, respectively) have emerged as powerful tools for oncology, particularly for liquid biopsy-based early detection. Thanks to its high sensitivity, specificity, and accuracy over other technologies, MS allows for the identification and quantification of a wide range of molecules from small metabolites to larger proteins.

Over the past few decades, MS-based proteomics has matured into a robust, high throughput platform with ever-increasing resolution and acquisition speed, enabling the quantification of thousands of proteins and mapping of the proteome across multiple cancer types. In fact, genetic mutations common across multiple cancer types alter the proteins produced from such genes, leading to changes in cellular function that support pro-cancer cellular activities.

As a result, proteins serve as the critical link between the genotype and the phenotype of a disease. On the clinical front, MS-based proteomics is now used for other disease detection and therapeutic monitoring applications due to its multiplexing capacity and high throughput over conventional methods.²   Therefore, the stage is set for MS to deliver proteomics-based profiles for oncology-based applications as well.

Profiling the metabolome and lipidome

More recently, MS is being leveraged to profile the metabolome and lipidome, providing insight into tumor metabolism and the surrounding microenvironments. Metabolomics is widely regarded as the omics discipline that most closely reflects the snapshot of the disease phenotype, as metabolites and lipids reflect the cumulative changes occurring due to alterations in the genome, transcriptome, and proteome. Changes in these blood-based molecules, therefore, hold untapped potential for early-stage cancer diagnostics.

Of all the omics disciplines, the newest kid on the block is lipidomics, which has experienced research-based growth in the last few years thanks to major advances in MS technology and bioinformatics tools such as machine learning. Lipidomics can provide a highly detailed, personalized, and quantitative snapshot, capturing thousands of lipid species within a single liquid biopsy.

Lipids are critically linked to cancer biology, and the study of the lipidome allows for the characterization of lipid molecules and their roles in biological pathways and mechanisms tied to cancer development and metastasis.³

Through standardization and harmonization efforts,⁴ lipids have now become highly adaptable to clinical diagnostics.⁵ Whether individually or when combined with proteins and metabolites, lipidomics offers the potential for a powerful new tool in clinicians’ toolbox for early cancer detection: by characterizing the lipidome alongside the proteome and metabolome of patients with cancer, we can start to untangle the mechanisms that drive cancer biology.

From there, novel candidate biomarkers can be identified and ultimately translated into clinically actionable diagnostic endpoints.

At AOA Dx, Abigail McElhinny, PhD, is CSO, and Rachel Culp-Hill, PhD, serves as senior product scientist. Kim Ekroos, PhD, is founder and CEO at Lipidomics Consulting.

References

1. Global cancer burden growing, amidst mounting need for services.

2. Birhanu, A. G. Mass spectrometry-based proteomics as an emerging tool in clinical laboratories. Clin. Proteomics 20, 32 (2023).

3. Hou, M. et al. The strategic role of lipidomics in biomarker identification and diagnosis of gynecological diseases. Front. Endocrinol. 16, 1546512 (2025).

4. McDonald, J. G. et al. Introducing the Lipidomics Minimal Reporting Checklist. Nat. Metab. 4, 1086–1088 (2022).

5. Ekroos, K. et al. Lipid-based biomarkers for CVD, COPD, and aging – A translational perspective. Prog. Lipid Res. 78, 101030 (2020).