Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal

Tamborero, David; Dienstmann, Rodrigo; Rachid, Maan Haj; Boekel, Jorrit; Baird, Richard D.; Braña, Irene; Petris, Luigi De; Yachnin, Jeffrey; Massard, Christophe; Opdam, Frans; Schlenk, Richard F.; Vernieri, Claudio; Garralda, Elena; Masucci, Michele; Villalobos, Xenia; Chavarria, Elena; Calvo, Fabien; Fröhling, Stefan; Eggermont, Alexander M.M.; Apolone, Giovanni; Voest, Emile E.; Caldas, Carlos; Tabernero, Josep; Ernberg, Ingemar; Rodón, Jordi; Lehtiö, Janne

doi:10.1038/s41591-020-0969-2

Cited by 70 publications

(60 citation statements)

References 11 publications

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“…Modern proteomic platforms are ever increasing achievable depth, where analysis of whole mammalian tissue [ 216 – 220 ] or plasma [ 221 , 222 ] routinely results in 10,000 or 1,500 unique proteins quantified per sample respectively. Furthermore, advances continue in capacity to detect post-translational modifications [ 223 , 224 ], determine compartmental localization [ 225 ], and apply findings in clinical settings [ 226 ]. In a golden age of proteomic technological advances, studies of vitamin intake have not kept pace.…”

Section: Discussionmentioning

confidence: 99%

Systemic vitamin intake impacting tissue proteomes

Jeong

Vacanti

2020

Nutr Metab (Lond)

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The kinetics and localization of the reactions of metabolism are coordinated by the enzymes that catalyze them. These enzymes are controlled via a myriad of mechanisms including inhibition/activation by metabolites, compartmentalization, thermodynamics, and nutrient sensing-based transcriptional or post-translational regulation; all of which are influenced as a network by the activities of metabolic enzymes and have downstream potential to exert direct or indirect control over protein abundances. Considering many of these enzymes are active only when one or more vitamin cofactors are present; the availability of vitamin cofactors likely yields a systems-influence over tissue proteomes. Furthermore, vitamins may influence protein abundances as nuclear receptor agonists, antioxidants, substrates for post-translational modifications, molecular signal transducers, and regulators of electrolyte homeostasis. Herein, studies of vitamin intake are explored for their contribution to unraveling vitamin influence over protein expression. As a body of work, these studies establish vitamin intake as a regulator of protein abundance; with the most powerful demonstrations reporting regulation of proteins directly related to the vitamin of interest. However, as a whole, the field has not kept pace with advances in proteomic platforms and analytical methodologies, and has not moved to validate mechanisms of regulation or potential for clinical application.

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Section: Discussionmentioning

confidence: 99%

Systemic vitamin intake impacting tissue proteomes

Jeong

Vacanti

2020

Nutr Metab (Lond)

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“…BoB represents important advances in the design of clinical studies where patients are prescreened using a homogenized system. Over 600 patients have been screened, and the investigators meet on a weekly basis to discuss the results in these patients through CCE’s MTB Portal [ 66 ], which is an innovative support system to guide clinical decision making in precision oncology, built by the Karolinska Institutet, Stockholm (Sweden). This portal enables CCE investigators to perform important correlative studies including the Strategic Immuno‐Monitoring of Patient Therapy (SIMPATHY) [ 67 ], for the first module assessing atezolizumab in genomically selected populations.…”

Section: Infrastructure For Clinical and Prevention Trialsmentioning

confidence: 99%

The Porto European Cancer Research Summit 2021

et al. 2021

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Key stakeholders from the cancer research continuum met in May 2021 at the European Cancer Research Summit in Porto to discuss priorities and specific action points required for the successful implementation of the European Cancer Mission and Europe's Beating Cancer Plan (EBCP). Speakers presented a unified view about the need to establish high‐quality, networked infrastructures to decrease cancer incidence, increase the cure rate, improve patient's survival and quality of life, and deal with research and care inequalities across the European Union (EU). These infrastructures, featuring Comprehensive Cancer Centres (CCCs) as key components, will integrate care, prevention and research across the entire cancer continuum to support the development of personalized/precision cancer medicine in Europe. The three pillars of the recommended European infrastructures – namely translational research, clinical/prevention trials and outcomes research – were pondered at length. Speakers addressing the future needs of translational research focused on the prospects of multiomics assisted preclinical research, progress in Molecular and Digital Pathology, immunotherapy, liquid biopsy and science data. The clinical/prevention trial session presented the requirements for next‐generation, multicentric trials entailing unified strategies for patient stratification, imaging, and biospecimen acquisition and storage. The third session highlighted the need for establishing outcomes research infrastructures to cover primary prevention, early detection, clinical effectiveness of innovations, health‐related quality‐of‐life assessment, survivorship research and health economics. An important outcome of the Summit was the presentation of the Porto Declaration, which called for a collective and committed action throughout Europe to develop the cancer research infrastructures indispensable for fostering innovation and decreasing inequalities within and between member states. Moreover, the Summit guidelines will assist decision making in the context of a unique EU‐wide cancer initiative that, if expertly implemented, will decrease the cancer death toll and improve the quality of life of those confronted with cancer, and this is carried out at an affordable cost.

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“…They represent a crucial target for cancer treatment and are subject to many clinical and biological investigations. [3][4][5] Of note, a driver mutation can be selected through tumorigenesis but need not be required for cancer maintenance. In parallel, cells also accumulate neutral mutations, called passenger mutations, which confer no fitness advantage and are therefore not subject to natural selection.…”

Section: Introductionmentioning

confidence: 99%

To portray clonal evolution in blood cancer, count your stem cells

Lyne

Laplane

Perié

2021

Blood

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Clonal evolution, the process of expansion and diversification of mutated cells, plays an important role in cancer development, resistance and relapse. While clonal evolution is most often conceived of as driven by natural selection, recent studies uncovered that neutral evolution shapes clonal evolution in a significant proportion of solid cancers. In hematological malignancies, the interplay between neutral evolution and natural selection is also disputed. Because natural selection selects cells with a higher fitness-providing a growth advantage to some cells relative to others-the architecture of clonal evolution serves as indirect evidence to distinguish natural selection from neutral evolution and has been associated with different prognoses for the patient. Linear architecture, when the new mutant clone grows within the previous one, is distinctive of hematological malignancies and typically interpreted as driven by natural selection. Here we wish to discuss the role of natural selection and neutral evolution in the production of linear clonal architectures in hematological malignancies. While it is tempting to attribute linear evolution to natural selection, we argue that a lower number of contributing stem cells accompanied by genetic drift can also result in a linear pattern of evolution as illustrated by simulations of clonal evolution in hematopoietic stem cells. The number of stem cells contributing to long-term clonal evolution is not known in the pathological context and we advocate that estimating these numbers in the context of cancer and ageing is crucial to parsing out neutral evolution from natural selection, two processes that require different therapeutic strategies.

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Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal

Cited by 70 publications

References 11 publications

Systemic vitamin intake impacting tissue proteomes

Systemic vitamin intake impacting tissue proteomes

The Porto European Cancer Research Summit 2021

To portray clonal evolution in blood cancer, count your stem cells

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