The Challenge of Tumor Heterogeneity in Personalized Medicine

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Figure 1: Illustration of MALDI Guided SpatialOMx analysis of breast tumor biopsy. Pathologist-annotated tumor regions are further segmented by SCiLS Lab based on molecular phenotyping derived from MALDI based lipid imaging. A very narrow region of tumor segmented into three molecular sub-regions is targeted for removal by LCM into collections of ~2000 cells from each sub-region. PASEF enables high sensitivity 4D-Proteomics from 160 ng of peptides injected into the timsTOF fleX to characterize the proteomes of each of the cellular subpopulations distinguished by GO annotation.

by Andreas Sonnen, Assistant Professor at University Medical Center Utrecht, and Michael L. Easterling, Imaging Business Director, Bruker Daltonics

Cancer is the second leading cause of death worldwide, with 10 million people dying from it every year.1 Tools that facilitate accurate cancer diagnosis and support potential treatment, especially in the early stages of disease, can direct clinicians to more effective treatment procedures. The heterogeneity of tumors presents a significant challenge in developing effective personalized treatments. Tumor heterogeneity refers to the differences between tumor cells of one patient or in the same type of tumor among multiple patients, and these differences can involve genes and/or proteins within the tumor.2 It means that not all tumor cells behave in the same way with regard to treatment response but also in reaction to analytical tools, for example immunohistochemistry. Over time, cancers can become more heterogeneous and resistant, which makes the treatment process increasingly difficult, thus spatial imaging of whole tumor slides, primary tumor and metastases, becomes progressively important.3

Unmet need-based oncology research

Personalized medicine is an emerging approach, especially in oncology departments, for tumor treatment and identification of biomarkers that advance prevention, diagnosis, prognosis, and therapeutics. Moving away from a one-size-fits-all- approach could improve overall patient care and ultimately and ideally result in a tailored treatment plan. Continued technological advances in Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS) hold great promise for developing a deeper understanding of the complexity of tissues and diseases.

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