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Cancers
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Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy
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Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy

A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 22558

Special Issue Editors

Prof. Dr. Melanie Börries

E-Mail Website
Guest Editor
Institute of Medical Bioinformatics and Systems Medicine, Faculty of Medicine and Medical Center-University of Freiburg, 79110 Freiburg, Germany
Interests: system biology; mathematical models; big data/multi-omics; bioinformatics; medical informatics
Dr. Claudia Paret

E-Mail Website
Guest Editor
Pediatric Hematology/Oncology, Children's Hospital, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany
Interests: pediatric oncology; biology-driven cancer medicine; clinical translation; personalized medicine; immune-oncology; bioinformatics

Special Issue Information

Dear Colleagues,

The idea of adapting cancer therapy to the specific molecular features of a tumor is changing the way we treat cancer, especially advanced cancer. Such features are discussed in dedicated molecular tumor boards (MTB) in which experts from different fields (such as bioinformatics, molecular oncology, and molecular biology) work together with clinicians to select the best therapy for individual patients. Although this concept is finding its way in hospitals around the world, several limitations may make this approach ineffective. While the development of resistances is a logical limitation of targeted therapies, other challenges reflect our difficulty in dealing with multiple and often uncharacterized alterations, the lack of inhibitors for some driver mutations, and technological pitfalls.

In this Special Issue, we aim to present single and multicenter experience, to introduce new methodologies or algorithms for identifying actionable aberrations, and to discuss new theories on cancer biology that may translate in a clinical application.

Prof. Dr. Melanie Börries
Dr. Claudia Paret
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • targeted therapy
  • drug repositioning
  • biomarkers
  • basket trials
  • precision oncology
  • personalized medicine

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Published Papers (6 papers)

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Research

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14 pages, 1496 KiB  
Article
MIRACUM-Pipe: An Adaptable Pipeline for Next-Generation Sequencing Analysis, Reporting, and Visualization for Clinical Decision Making
by Patrick Metzger, Maria Elena Hess, Andreas Blaumeiser, Thomas Pauli, Vincent Schipperges, Ralf Mertes, Jan Christoph, Philipp Unberath, Niklas Reimer, Raphael Scheible, Anna L. Illert, Hauke Busch, Geoffroy Andrieux and Melanie Boerries
Cancers 2023, 15(13), 3456; https://doi.org/10.3390/cancers15133456 - 1 Jul 2023
Cited by 11 | Viewed by 3123
Abstract
(1) Background: Next-generation sequencing (NGS) of patients with advanced tumors is becoming an established method in Molecular Tumor Boards. However, somatic variant detection, interpretation, and report generation, require in-depth knowledge of both bioinformatics and oncology. (2) Methods: MIRACUM-Pipe combines many individual tools into [...] Read more.
(1) Background: Next-generation sequencing (NGS) of patients with advanced tumors is becoming an established method in Molecular Tumor Boards. However, somatic variant detection, interpretation, and report generation, require in-depth knowledge of both bioinformatics and oncology. (2) Methods: MIRACUM-Pipe combines many individual tools into a seamless workflow for comprehensive analyses and annotation of NGS data including quality control, alignment, variant calling, copy number variation estimation, evaluation of complex biomarkers, and RNA fusion detection. (3) Results: MIRACUM-Pipe offers an easy-to-use, one-prompt standardized solution to analyze NGS data, including quality control, variant calling, copy number estimation, annotation, visualization, and report generation. (4) Conclusions: MIRACUM-Pipe, a versatile pipeline for NGS, can be customized according to bioinformatics and clinical needs and to support clinical decision-making with visual processing and interactive reporting. Full article
(This article belongs to the Special Issue Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy)
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22 pages, 3250 KiB  
Article
GD2 Expression in Medulloblastoma and Neuroblastoma for Personalized Immunotherapy: A Matter of Subtype
by Claudia Paret, Arsenij Ustjanzew, Sara Ersali, Larissa Seidmann, Richard Jennemann, Nicole Ziegler, Khalifa El Malki, Alexandra Russo, Arthur Wingerter, Franziska Ortmüller, Angelina Bornas, Pia Charlotte Wehling, Adina Lepădatu, Malte Ottenhausen, Wilfried Roth, Clemens Sommer, Barbara Fliss, Katrin B. M. Frauenknecht, Roger Sandhoff and Jörg Faber
Cancers 2022, 14(24), 6051; https://doi.org/10.3390/cancers14246051 - 8 Dec 2022
Cited by 7 | Viewed by 3917
Abstract
Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 [...] Read more.
Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes. Full article
(This article belongs to the Special Issue Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy)
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12 pages, 3181 KiB  
Article
Identification of Disparities in Personalized Cancer Care—A Joint Approach of the German WERA Consortium
by Florian Lüke, Florian Haller, Kirsten Utpatel, Markus Krebs, Norbert Meidenbauer, Alexander Scheiter, Silvia Spoerl, Daniel Heudobler, Daniela Sparrer, Ulrich Kaiser, Felix Keil, Christoph Schubart, Lars Tögel, Sabine Einhell, Wolfgang Dietmaier, Ralf Huss, Sebastian Dintner, Sebastian Sommer, Frank Jordan, Maria-Elisabeth Goebeler, Michaela Metz, Diana Haake, Mithun Scheytt, Elena Gerhard-Hartmann, Katja Maurus, Stephanie Brändlein, Andreas Rosenwald, Arndt Hartmann, Bruno Märkl, Hermann Einsele, Andreas Mackensen, Wolfgang Herr, Volker Kunzmann, Ralf Bargou, Matthias W. Beckmann, Tobias Pukrop, Martin Trepel, Matthias Evert, Rainer Claus and Alexander Kerscheradd Show full author list remove Hide full author list
Cancers 2022, 14(20), 5040; https://doi.org/10.3390/cancers14205040 - 14 Oct 2022
Cited by 10 | Viewed by 3076
Abstract
(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB [...] Read more.
(1) Background: molecular tumor boards (MTBs) are crucial instruments for discussing and allocating targeted therapies to suitable cancer patients based on genetic findings. Currently, limited evidence is available regarding the regional impact and the outreach component of MTBs; (2) Methods: we analyzed MTB patient data from four neighboring Bavarian tertiary care oncology centers in Würzburg, Erlangen, Regensburg, and Augsburg, together constituting the WERA Alliance. Absolute patient numbers and regional distribution across the WERA-wide catchment area were weighted with local population densities; (3) Results: the highest MTB patient numbers were found close to the four cancer centers. However, peaks in absolute patient numbers were also detected in more distant and rural areas. Moreover, weighting absolute numbers with local population density allowed for identifying so-called white spots—regions within our catchment that were relatively underrepresented in WERA MTBs; (4) Conclusions: investigating patient data from four neighboring cancer centers, we comprehensively assessed the regional impact of our MTBs. The results confirmed the success of existing collaborative structures with our regional partners. Additionally, our results help identifying potential white spots in providing precision oncology and help establishing a joint WERA-wide outreach strategy. Full article
(This article belongs to the Special Issue Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy)
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17 pages, 1490 KiB  
Article
Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board
by Thomas S. Tarawneh, Fiona R. Rodepeter, Julia Teply-Szymanski, Petra Ross, Vera Koch, Clemens Thölken, Jonas A. Schäfer, Niklas Gremke, Hildegard I. D. Mack, Judith Gold, Jorge Riera-Knorrenschild, Christian Wilhelm, Anja Rinke, Martin Middeke, Andreas Klemmer, Marcel Romey, Akira Hattesohl, Moritz Jesinghaus, Christian Görg, Jens Figiel, Ho-Ryun Chung, Thomas Wündisch, Andreas Neubauer, Carsten Denkert and Elisabeth K. M. Mackadd Show full author list remove Hide full author list
Cancers 2022, 14(18), 4430; https://doi.org/10.3390/cancers14184430 - 12 Sep 2022
Cited by 11 | Viewed by 4006
Abstract
Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. Methods: We retrospectively analyzed all patients [...] Read more.
Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. Methods: We retrospectively analyzed all patients referred to our center’s Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel’s target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS. Results: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy (n = 30) had significantly longer progression-free survival than patients treated with other therapies (n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits. Conclusion: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches. Full article
(This article belongs to the Special Issue Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy)
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Review

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19 pages, 753 KiB  
Review
Role of the Molecular Tumor Board for the Personalized Treatment of Patients with Metastatic Breast Cancer: A Focus on the State of the Art in Italy
by Azzurra Irelli, Sofia Chiatamone Ranieri, Daniela Di Giacomo, Sara Malatesta, Leonardo Valerio Patruno, Alessandra Tessitore, Edoardo Alesse and Katia Cannita
Cancers 2023, 15(6), 1727; https://doi.org/10.3390/cancers15061727 - 12 Mar 2023
Cited by 11 | Viewed by 3198
Abstract
Molecular tumor boards (MTBs) are multidisciplinary groups that combine molecular and clinical data from cancer patients in order to formulate treatment recommendations for precision medicine. To date, there is insufficient data to support the use of singleplex or next-generation sequencing (NGS) technologies to [...] Read more.
Molecular tumor boards (MTBs) are multidisciplinary groups that combine molecular and clinical data from cancer patients in order to formulate treatment recommendations for precision medicine. To date, there is insufficient data to support the use of singleplex or next-generation sequencing (NGS) technologies to select first-line therapy for patients with metastatic breast cancer (MBC), but considering the high number of level II alterations, according to the ESMO scale for clinical actionability of molecular targets (ESCAT), it is suggested to include patients in molecular screening programs in order to be able to offer targeted therapies for specific genomic alterations. This article aims at reviewing the most recent literature related to the most used methodologies/approaches for molecular diagnostics and variants’ classification, summarizing the internationally published molecular screening studies in support of MTB activity and, in the end, discussing MTBs’ current position and role in Italy, the number of which is increasing, also thanks to the thrust of institutions. Full article
(This article belongs to the Special Issue Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy)
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18 pages, 700 KiB  
Review
Challenges and Obstacles in Applying Therapeutical Indications Formulated in Molecular Tumor Boards
by Edoardo Crimini, Matteo Repetto, Paolo Tarantino, Liliana Ascione, Gabriele Antonarelli, Elena Guerini Rocco, Massimo Barberis, Luca Mazzarella and Giuseppe Curigliano
Cancers 2022, 14(13), 3193; https://doi.org/10.3390/cancers14133193 - 29 Jun 2022
Cited by 14 | Viewed by 2941
Abstract
Considering the rapid improvement of cancer drugs’ efficacy and the discovery of new molecular targets, the formulation of therapeutical indications based on the multidisciplinary approach of MTB is becoming increasingly important for attributing the correct salience to the targets identified in a single [...] Read more.
Considering the rapid improvement of cancer drugs’ efficacy and the discovery of new molecular targets, the formulation of therapeutical indications based on the multidisciplinary approach of MTB is becoming increasingly important for attributing the correct salience to the targets identified in a single patient. Nevertheless, one of the biggest stumbling blocks faced by MTBs is not the bare indication, but its implementation in the clinical practice. Indeed, administering the drug suggested by MTB deals with some relevant difficulties: the economical affordability and geographical accessibility represent some of the major limits in the patient’s view, while bureaucracy and regulatory procedures are often a disincentive for the physicians. In this review, we explore the current literature reporting MTB experiences and precision medicine clinical trials, focusing on the challenges that authors face in applying their therapeutical indications. Furthermore, we analyze and discuss some of the solutions devised to overcome these difficulties to support the MTBs in finding the most suitable solution for their specific situation. In conclusion, we strongly encourage regulatory agencies and pharmaceutical companies to develop effective strategies with medical centers implementing MTBs to facilitate access to innovative drugs and thereby allow broader therapeutical opportunities to patients. Full article
(This article belongs to the Special Issue Molecular Tumor Boards: Promise and Limitations for Personalized Cancer Therapy)
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