bims-ovdlit 2021-08-15 papers

Issue of 2021–08–15
five papers selected by
Lara Paracchini, Humanitas Research

Semin Oncol. 2021 Jul 14. pii: S0093-7754(21)00038-5. [Epub ahead of print]

Liquid Biopsy, the hype vs. hope in molecular and clinical oncology.

Abhishek Mohanty, Sambit K Mohanty, Sipra Rout, Chinmaya Pani.

The molecular landscape of tumors has been traditionally established using a biopsy or resection specimens. These modalities result in sampling bias that offer only a single snapshot of tumor heterogeneity. Over the last decade intensive research towards alleviating such a bias and obtaining an integral yet accurate portrait of the tumors, evolved to the use of established molecular and genetic analysis using blood and several other body fluids, such as urine, saliva, and pleural effusions as liquid biopsies. Genomic profiling of the circulating markers including circulating cell-free tumor DNA (ctDNA), circulating tumor cells (CTCs) or even RNA, proteins, and lipids constituting exosomes, have facilitated the diligent monitoring of response to treatment, allowed one to follow the emergence of drug resistance, and enumerate minimal residual disease. The prevalence of tumor educated platelets (TEPs) and our understanding of how tumor cells influence platelets are beginning to unearth TEPs as a potentially dynamic component of liquid biopsies. Here, we review the biology, methodology, approaches, and clinical applications of biomarkers used to assess liquid biopsies. The current review addresses recent technological advances and different forms of liquid biopsy along with upcoming challenges and how they can be integrated to get the best possible tumor-derived genetic information that can be leveraged to more precise therapies for patient as liquid biopsies become increasingly routine in clinical practice.

Keywords: Circulating tumor DNA (ctDNA); Circulating tumor RNA (ctRNA); Circulating tumor cells (CTCs); Liquid Biopsy; Tumor Educated Platelets, TEPs; tissue biopsy; tumor metastasis

DOI: https://doi.org/10.1053/j.seminoncol.2021.06.002

Clin Radiol. 2021 Aug 10. pii: S0009-9260(21)00374-3. [Epub ahead of print]

Circulating tumour DNA for clinicians: current and future clinical applications.

M K Thompson, D Gale, J D Brenton.

This review introduces clinicians to the basic concepts of the biology of circulating tumour DNA (ctDNA), which is required to understand clinical use of ctDNA technology. We provide an overview of how new technology has improved the sensitivity of ctDNA detection over the last decade and the available techniques for ctDNA analysis including whole-genome sequencing (WGS), targeted cancer-associated gene panels, and methylation analysis. We discuss the most recent evidence from clinical trials for ctDNA in patient care including precision treatment of advanced cancers, disease monitoring, improving adjuvant treatment, and screening for early detection of cancer. Finally, we outline how ctDNA is likely to directly impact radiologists, and identify further research required for ctDNA to progress into routine clinical application.

DOI: https://doi.org/10.1016/j.crad.2021.07.005

Front Oncol. 2021 ;11 692322

Application of Data Science in Circulating Tumor DNA Detection: A Promising Avenue Towards Liquid Biopsy.

Ming Li, Sisi Xie, Chenyu Lu, Lingyun Zhu, Lvyun Zhu.

The circulating tumor DNA (ctDNA), as a promising biomarker of liquid biopsy, has potential clinical relevance on the molecular diagnosis and monitoring of cancer. However, the trace concentration level of ctDNA in the peripheral blood restricts its extensive clinical application. Recently, high-throughput-based methodologies have been leveraged to improve the sensitivity and specificity of ctDNA detection, showing a promising avenue towards liquid biopsy. This review briefly summarizes the high-throughput data features concerned by current ctDNA detection strategies and the technical obstacles, potential solutions, and clinical relevance of current ctDNA profiling technologies. We also highlight future directions improving the limit of detection of ctDNA for better clinical application. This review may serve as a reference for the crosslinks between data science and ctDNA-based liquid biopsy, benefiting clinical translation in advanced cancer diagnosis.

Keywords: cancer diagnosis; ctDNA detection; data science; liquid biopsy; technological advancement

DOI: https://doi.org/10.3389/fonc.2021.692322

Nature. 2021 08;596(7871): 211-220

Exploring tissue architecture using spatial transcriptomics.

Anjali Rao, Dalia Barkley, Gustavo S França, Itai Yanai.

Deciphering the principles and mechanisms by which gene activity orchestrates complex cellular arrangements in multicellular organisms has far-reaching implications for research in the life sciences. Recent technological advances in next-generation sequencing- and imaging-based approaches have established the power of spatial transcriptomics to measure expression levels of all or most genes systematically throughout tissue space, and have been adopted to generate biological insights in neuroscience, development and plant biology as well as to investigate a range of disease contexts, including cancer. Similar to datasets made possible by genomic sequencing and population health surveys, the large-scale atlases generated by this technology lend themselves to exploratory data analysis for hypothesis generation. Here we review spatial transcriptomic technologies and describe the repertoire of operations available for paths of analysis of the resulting data. Spatial transcriptomics can also be deployed for hypothesis testing using experimental designs that compare time points or conditions-including genetic or environmental perturbations. Finally, spatial transcriptomic data are naturally amenable to integration with other data modalities, providing an expandable framework for insight into tissue organization.

DOI: https://doi.org/10.1038/s41586-021-03634-9

Nat Rev Cancer. 2021 Aug 10.

Targeting the DNA damage response in immuno-oncology: developments and opportunities.

Roman M Chabanon, Mathieu Rouanne, Christopher J Lord, Jean-Charles Soria, Philippe Pasero, Sophie Postel-Vinay.

Immunotherapy has revolutionized cancer treatment and substantially improved patient outcome with regard to multiple tumour types. However, most patients still do not benefit from such therapies, notably because of the absence of pre-existing T cell infiltration. DNA damage response (DDR) deficiency has recently emerged as an important determinant of tumour immunogenicity. A growing body of evidence now supports the concept that DDR-targeted therapies can increase the antitumour immune response by (1) promoting antigenicity through increased mutability and genomic instability, (2) enhancing adjuvanticity through the activation of cytosolic immunity and immunogenic cell death and (3) favouring reactogenicity through the modulation of factors that control the tumour-immune cell synapse. In this Review, we discuss the interplay between the DDR and anticancer immunity and highlight how this dynamic interaction contributes to shaping tumour immunogenicity. We also review the most innovative preclinical approaches that could be used to investigate such effects, including recently developed ex vivo systems. Finally, we highlight the therapeutic opportunities presented by the exploitation of the DDR-anticancer immunity interplay, with a focus on those in early-phase clinical development.

DOI: https://doi.org/10.1038/s41568-021-00386-6