14 CHAPTER 1 are often core needle biopsies, with a maximum tissue yield of only 3.5 – 7 mg when using a 16-gauge core needle37. In recent years, the omics techniques have improved tremendously, resulting in a general lowering of minimally required quantity of tissue. Whole genome- and whole transcriptome sequencing can already be performed on a single cell38-40. In the field of phosphoproteomics, important steps have been made to optimize the techniques, to facilitate analysis of small clinical samples41. Single-cell mass spectrometry-based phosphoproteomics is considered a promising opportunity for improving our understanding of individual tumor biology and facilitating phosphoproteomics-based therapy selection for individual patients in the future42,43. Furthermore, a standardized suitable method of processing and handling the acquired tissue specimen is fundamentally important to allow for a comprehensive multi-layer analysis of cancer tissue. In the past, biopsy samples were often collected in buffers that stabilized DNA and RNA, but essentially rendering the tissue useless for proteomics analysis32. Instead, high-quality fresh frozen tumor samples are required44. Standardized operating procedures for handling and preservation of the tissue are indispensable, since differences in pre-analytical handling can generate conflicting research results due to heterogeneity in the quality of samples and associated data45,46. Moreover, posttranslational modifications may be affected by certain handling and storage conditions, such as cold ischemia time47-50 and possibly freezing rate51-53. Standardized high-quality preservation of biospecimens, in order to harness the most accurate genomic, transcriptomic and protein expression properties of the tissue, is a basic requirement for the generation of these complex multi-omics data46. An even bigger challenge may be the urgent need for the development of an integrated bioinformatics pipeline for a comprehensive analysis of these high-throughput molecular assays32,54. Such an integrated approach may further increase our understanding of cancer biology and support biomarker discovery and drug repurposing55,56, both essential for the practice and advancement of precision oncology. TREATMENT SELECTION TRIALS Working towards a histology-agnostic biomarker-centric approach, many precision oncology clinical trials now focus on the use of registered or experimental (combinations of) targeted agents solely based on the presence of a validated biomarker, while evaluating the effect in the context of histology. New trial designs have been developed to investigate even modest signs of clinical activity of these targeted agents in small subgroups of patients with cancer. Many of these basket-, umbrella and N-of-1-trials have been conducted in the past ten years57, some living up to the promise of precision medicine, and others reporting disappointing results58-70. Tsimberidou et al have reviewed and summarized all these completed and ongoing trials and their distinctive features and outcomes21. A fundamental question in precision oncology remains how to select the right treatment for the right patient at the right time. An important factor contributing to the success of a precision oncology approach may be the actual process of treatment selection and the arguments for prioritizing one treatment over another.
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