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Cancers
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Precision Medicine in Thoracic Oncology
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Precision Medicine in Thoracic Oncology

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 11736

Special Issue Editors

Prof. Dr. Michele Milella

E-Mail Website
Guest Editor
Section of Oncology, Department of Medicine, University of Verona Hospital Trust, 37134 Verona, Italy
Interests: precision oncology; molecularly targeted therapy; lung and thoracic cancers; hepato-bilio-pancreatic cancers; kidney cancer; neuroendocrine tumors
Special Issues, Collections and Topics in MDPI journals
Dr. Andrea Bonetti

E-Mail Website
Guest Editor
Department of Medical Oncology, AULSS 9 Scaligera, 37100 Verona, Italy
Interests: women’s cancers (breast and gynecological); gastro-intestinal cancers; pharmaco-economy
Dr. Jessica Menis

E-Mail Website
Guest Editor
Department of Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
Interests: non-small cancer cells; lung cancer

Special Issue Information

Dear Colleagues,

The past twenty years have witnessed an unprecedented development of technologies, which allow for a more precise definition of the genetic make-up of solid and hematological cancers, promoting the identification of molecular alterations consistently expressed in some kinds of tumors quite often characterized by a peculiar clinical behavior and response to target treatments. Among the tumors for which an extensive evaluation of genetic alterations has been rewarding are lung cancers, especially adenocarcinomas, now subclassified according to the expression of specific markers, which drive a personalized attempt to cure. In this Special Issue of Cancers, we aim to collect contributions not only on the broader topic of lung cancer, but also regarding much less common thoracic neoplasms such as thymoma, mesothelioma, and neuroendocrine tumors. Contributions can be in the form of original articles, reviews, or commentaries, aimed at providing a comprehensive update on ideas, discoveries, technologies, and approaches that are bringing precision oncology to the bedside of patients diagnosed with thoracic cancers.  

Prof. Dr. Michele Milella
Dr. Andrea Bonetti
Dr. Jessica Menis 
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 short 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

  • precision medicine
  • thoracic oncology
  • lung cancer
  • thymoma
  • mesothelioma
  • thoracic NETs
  • molecularly targeted therapy
  • immunotherapy
  • biomarkers

Published Papers (5 papers)

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Research

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12 pages, 841 KiB  
Article
Improvement of Lung NET Management through Standardized Care—A Swiss Nationwide Observational Study
by Moira Schmidlin, Samira M. Sadowski, Alexander Siebenhüner, Damian Wild, Emanuel Christ and Julie Refardt
Cancers 2023, 15(8), 2270; https://doi.org/10.3390/cancers15082270 - 13 Apr 2023
Viewed by 1515
Abstract
Typical (TC) and atypical carcinoids (AC) are the most common neuroendocrine tumors (NETs) of the lung. Because these tumors are rare, their management varies widely among Swiss centers. Our aim was to compare the management of Swiss patients before and after the publication [...] Read more.
Typical (TC) and atypical carcinoids (AC) are the most common neuroendocrine tumors (NETs) of the lung. Because these tumors are rare, their management varies widely among Swiss centers. Our aim was to compare the management of Swiss patients before and after the publication of the expert consensus of the European Neuroendocrine Tumor Society (ENETS) in 2015. We used data from the Swiss NET registry from 2009 to 2021 with patients with TC and AC. Survival analysis was performed using the Kaplan–Meier method and log-rank test. Overall, 238 patients were included, 76% (180) thereof with TC and 24% (58) with AC, including 155 patients before and 83 patients after 2016. An increase in the use of functional imaging was observed, 16% (25) before and 35% (29) after 2016, p < 0.001. The presence of SST2A-receptors was determined more often: 32% (49 times) before 2016 and 47% (39 times) after, p = 0.019. Concerning therapy, higher removal of lymph nodes after 2016 was observed, 54% (83) before versus 78% (65) after, p < 0.001. Median overall survival for patients with AC was significantly shorter, with 89 months compared to 157 months for patients with TC, p < 0.001. While the implementation of a more standardized approach was observed over the years, there is still room for amelioration in the management of TC and AC in Switzerland. Full article
(This article belongs to the Special Issue Precision Medicine in Thoracic Oncology)
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14 pages, 2750 KiB  
Article
Phosphoproteomic Analysis Identifies TYRO3 as a Mediator of Sunitinib Resistance in Metastatic Thymomas
by Stefan Küffer, Jessica Grabowski, Satoru Okada, Nikolai Sojka, Stefan Welter, Alexander von Hammerstein-Equord, Marc Hinterthaner, Lucia Cordes, Xenia von Hahn, Denise Müller, Christian Sauer, Hanibal Bohnenberger, Alexander Marx and Philipp Ströbel
Cancers 2022, 14(19), 4762; https://doi.org/10.3390/cancers14194762 - 29 Sep 2022
Cited by 4 | Viewed by 1736
Abstract
Background: After initially responding to empiric radio-chemotherapy, most advanced thymomas (TH) and thymic carcinomas (TC) become refractory and require second-line therapy. The multi-target receptor tyrosine kinase (RTK) inhibitor, sunitinib, is one of the few options, especially in patients with thymic carcinomas, and has [...] Read more.
Background: After initially responding to empiric radio-chemotherapy, most advanced thymomas (TH) and thymic carcinomas (TC) become refractory and require second-line therapy. The multi-target receptor tyrosine kinase (RTK) inhibitor, sunitinib, is one of the few options, especially in patients with thymic carcinomas, and has resulted in partial remissions and prolonged overall survival. However, sunitinib shows variable activity in thymomas, and not all patients benefit equally. A better understanding of its mode of action and the definition of predictive biomarkers would help select patients who profit most. Methods: Six cell lines were treated with sunitinib in vitro. Cell viability was measured by MTS assay and used to define in vitro responders and non-responders. A quantitative real-time assay simultaneously measuring the phosphorylation of 144 tyrosine kinase substrates was used to correlate cell viability with alterations of the phospho-kinome, calculate a sunitinib response index (SRI), and impute upstream tyrosine kinases. Sunitinib was added to protein lysates of 29 malignant TH and TC. Lysates were analyzed with the same phosphorylation assay. The SRI tentatively classified cases into potential clinical responders and non-responders. In addition, the activation patterns of 44 RTKs were studied by phospho-RTK arrays in 37 TH and TC. Results: SRI application separated thymic epithelial tumors (TET) in potential sunitinib responders and resistant cases. Upstream kinase prediction identified multiple RTKs potentially involved in sunitinib response, many of which were subsequently shown to be differentially overexpressed in TH and TC. Among these, TYRO3/Dtk stood out since it was exclusively present in metastatic TH. The function of TYRO3 as a mediator of sunitinib resistance was experimentally validated in vitro. Conclusions: Using indirect and direct phosphoproteomic analyses to predict sunitinib response in malignant TET, we have shown that TH and TC express multiple important sunitinib target RTKs. Among these, TYRO3 was identified as a potent mediator of sunitinib resistance activity, specifically in metastatic TH. TYRO3 may thus be both a novel biomarker of sunitinib resistance and a potential therapeutic target in advanced thymomas and thymic carcinomas. Full article
(This article belongs to the Special Issue Precision Medicine in Thoracic Oncology)
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Review

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14 pages, 281 KiB  
Review
Precision Surgery in NSCLC
by Giorgio Cannone, Giovanni Maria Comacchio, Giulia Pasello, Eleonora Faccioli, Marco Schiavon, Andrea Dell’Amore, Marco Mammana and Federico Rea
Cancers 2023, 15(5), 1571; https://doi.org/10.3390/cancers15051571 - 3 Mar 2023
Cited by 4 | Viewed by 1780
Abstract
Non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. This is mostly because the majority of lung cancers are discovered in advanced stages. In the era of conventional chemotherapy, the prognosis of advanced NSCLC was grim. Important [...] Read more.
Non-small cell lung cancer (NSCLC) is still one of the leading causes of death worldwide. This is mostly because the majority of lung cancers are discovered in advanced stages. In the era of conventional chemotherapy, the prognosis of advanced NSCLC was grim. Important results have been reported in thoracic oncology since the discovery of new molecular alterations and of the role of the immune system. The advent of new therapies has radically changed the approach to lung cancer for a subset of patients with advanced NSCLC, and the concept of incurable disease is still changing. In this setting, surgery seems to have developed a role of rescue therapy for some patients. In precision surgery, the decision to perform surgical procedures is tailored to the individual patient; taking into consideration not only clinical stage, but also clinical and molecular features. Multimodality treatments incorporating surgery, immune checkpoint inhibitors, or targeted agents are feasible in high volume centers with good results in terms of pathologic response and patient morbidity. Thanks to a better understanding of tumor biology, precision thoracic surgery will facilitate optimal and individualized patient selection and treatment, with the goal of improving the outcomes of patients affected by NSCLC. Full article
(This article belongs to the Special Issue Precision Medicine in Thoracic Oncology)
23 pages, 907 KiB  
Review
The Prognostic and Therapeutic Potential of DNA Damage Repair Pathway Alterations and Homologous Recombination Deficiency in Lung Cancer
by Karam Khaddour, Manuel Felipe Fernandez, Marsel Khabibov, Airat Garifullin, Danielle Dressler, Iuliia Topchu, Jyoti D. Patel, Frank Weinberg and Yanis Boumber
Cancers 2022, 14(21), 5305; https://doi.org/10.3390/cancers14215305 - 28 Oct 2022
Cited by 3 | Viewed by 2512
Abstract
Lung cancer remains the second most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. The mapping of genomic alterations and their role in lung-cancer progression has been followed by the development of new therapeutic options. Several novel drugs, such as [...] Read more.
Lung cancer remains the second most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. The mapping of genomic alterations and their role in lung-cancer progression has been followed by the development of new therapeutic options. Several novel drugs, such as targeted therapy and immunotherapy, have significantly improved outcomes. However, many patients with lung cancer do not benefit from existing therapies or develop progressive disease, leading to increased morbidity and mortality despite initial responses to treatment. Alterations in DNA-damage repair (DDR) genes represent a cancer hallmark that impairs a cell’s ability to prevent deleterious mutation accumulation and repair. These alterations have recently emerged as a therapeutic target in breast, ovarian, prostate, and pancreatic cancers. The role of DDR alterations remains largely unknown in lung cancer. Nevertheless, recent research efforts have highlighted a potential role of some DDR alterations as predictive biomarkers of response to treatment. Despite the failure of PARP inhibitors (main class of DDR targeting agents) to improve outcomes in lung cancer patients, there is some evidence suggesting a role of PARP inhibitors and other DDR targeting agents in benefiting a distinct subset of lung cancer patients. In this review, we will discuss the existing literature on DDR alterations and homologous recombination deficiency (HRD) state as predictive biomarkers and therapeutic targets in both non-small cell lung and small cell lung cancer. Full article
(This article belongs to the Special Issue Precision Medicine in Thoracic Oncology)
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22 pages, 1583 KiB  
Review
Lung Cancer Organoids: The Rough Path to Personalized Medicine
by Rachele Rossi, Maria Laura De Angelis, Eljona Xhelili, Giovanni Sette, Adriana Eramo, Ruggero De Maria, Ursula Cesta Incani, Federica Francescangeli and Ann Zeuner
Cancers 2022, 14(15), 3703; https://doi.org/10.3390/cancers14153703 - 29 Jul 2022
Cited by 14 | Viewed by 3479
Abstract
Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10–20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high [...] Read more.
Lung cancer is the leading cause of cancer death worldwide. Despite significant advances in research and therapy, a dismal 5-year survival rate of only 10–20% urges the development of reliable preclinical models and effective therapeutic tools. Lung cancer is characterized by a high degree of heterogeneity in its histology, a genomic landscape, and response to therapies that has been traditionally difficult to reproduce in preclinical models. However, the advent of three-dimensional culture technologies has opened new perspectives to recapitulate in vitro individualized tumor features and to anticipate treatment efficacy. The generation of lung cancer organoids (LCOs) has encountered greater challenges as compared to organoids derived from other tumors. In the last two years, many efforts have been dedicated to optimizing LCO-based platforms, resulting in improved rates of LCO production, purity, culture timing, and long-term expansion. However, due to the complexity of lung cancer, further advances are required in order to meet clinical needs. Here, we discuss the evolution of LCO technology and the use of LCOs in basic and translational lung cancer research. Although the field of LCOs is still in its infancy, its prospective development will likely lead to new strategies for drug testing and biomarker identification, thus allowing a more personalized therapeutic approach for lung cancer patients. Full article
(This article belongs to the Special Issue Precision Medicine in Thoracic Oncology)
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