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Precision Medicine in Oncology 2.0
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Precision Medicine in Oncology 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 September 2024) | Viewed by 8206

Special Issue Editor

Dr. Luís Lima

E-Mail Website1 Website2
Guest Editor
1. Experimental Pathology and Therapeutics Group, Research Center of IPO Porto (CI-IPOP), Porto, Portugal
2. RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto), Porto, Portugal
3. Porto Comprehensive Cancer Center (Porto.CCC), 4200-072 Porto, Portugal
Interests: oncology; biomedical science; genotyping; cancer research; biomarker discovery and validation; bladder cancer; liquid biopsies; CTC identification; gastrointestinal cancer; colorectal screening; fecal biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Precision medicine in oncology is used to treat and prevent cancer and considers individual gene variability, the environment, and people’s lifestyles. It does not technically imply the development of patient-specific pharmaceuticals or medical devices, but rather the ability to divide people into subpopulations based on their disease susceptibility, the biology or prognosis, or their reaction to a certain therapy. Thus, preventive or therapeutic actions can focus on individuals who will benefit, saving money and reducing the adverse effects.

In this perspective, this Special Issue of IJMS seeks to compile a series of original research articles and comprehensive reviews encompassing all aspects of “Precision Medicine in Oncology”.

Investigations into a myriad of fields, such as biomarker discovery; “omics” approaches, e.g., pharmacogenomics, proteomics, genomics, and transcriptomics; or big data analysis, are welcome. Works that help decipher molecular changes and identify the biomarkers and predictors of prognosis and behavior, as well as advances in therapeutic options and resistance mechanisms are also topics of special interest.

Contributions on other significant topics that further enhance our understanding of molecular immunotherapy and targeted therapy in cancer are also welcome.

Dr. Luís Lima
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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 oncology
  • biomarkers
  • data analysis
  • multiomics
  • patient stratification
  • molecular profilimg
  • targeted therateutics
  • immunotherapy

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Published Papers (5 papers)

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Research

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19 pages, 2076 KiB  
Article
Discovery of Plasma Lipids as Potential Biomarkers Distinguishing Breast Cancer Patients from Healthy Controls
by Desmond Li, Kerry Heffernan, Forrest C. Koch, David A. Peake, Dana Pascovici, Mark David, Cheka Kehelpannala, G. Bruce Mann, David Speakman, John Hurrell, Simon Preston, Fatemeh Vafaee and Amani Batarseh
Int. J. Mol. Sci. 2024, 25(21), 11559; https://doi.org/10.3390/ijms252111559 - 28 Oct 2024
Viewed by 903
Abstract
The development of a sensitive and specific blood test for the early detection of breast cancer is crucial to improve screening and patient outcomes. Existing methods, such as mammography, have limitations, necessitating the exploration of alternative approaches, including circulating factors. Using 598 prospectively [...] Read more.
The development of a sensitive and specific blood test for the early detection of breast cancer is crucial to improve screening and patient outcomes. Existing methods, such as mammography, have limitations, necessitating the exploration of alternative approaches, including circulating factors. Using 598 prospectively collected blood samples, a multivariate plasma-derived lipid biomarker signature was developed that can distinguish healthy control individuals from those with breast cancer. Liquid chromatography with high-resolution and tandem mass spectrometry (LC-MS/MS) was employed to identify lipids for both extracellular vesicle-derived and plasma-derived signatures. For each dataset, we identified a signature of 20 lipids using a robust, statistically rigorous feature selection algorithm based on random forest feature importance applied to cross-validated training samples. Using an ensemble of machine learning models, the plasma 20-lipid signature generated an area under the curve (AUC) of 0.95, sensitivity of 0.91, and specificity of 0.79. The results from this study indicate that lipids extracted from plasma can be used as target analytes in the development of assays to detect the presence of early-stage breast cancer. Full article
(This article belongs to the Special Issue Precision Medicine in Oncology 2.0)
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18 pages, 1826 KiB  
Article
Novel Blood Biomarkers for Response Prediction and Monitoring of Stereotactic Ablative Radiotherapy and Immunotherapy in Metastatic Oligoprogressive Lung Cancer
by Juan Zafra, Juan Luis Onieva, Javier Oliver, María Garrido-Barros, Andrea González-Hernández, Beatriz Martínez-Gálvez, Alicia Román, Rafael Ordóñez-Marmolejo, Elisabeth Pérez-Ruiz, José Carlos Benítez, Andrés Mesas, Andrés Vera, Rodolfo Chicas-Sett, Antonio Rueda-Domínguez and Isabel Barragán
Int. J. Mol. Sci. 2024, 25(8), 4533; https://doi.org/10.3390/ijms25084533 - 20 Apr 2024
Cited by 2 | Viewed by 2072
Abstract
Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of [...] Read more.
Up to 80% of patients under immune checkpoint inhibitors (ICI) face resistance. In this context, stereotactic ablative radiotherapy (SABR) can induce an immune or abscopal response. However, its molecular determinants remain unknown. We present early results of a translational study assessing biomarkers of response to combined ICI and SABR (I-SABR) in liquid biopsy from oligoprogressive patients in a prospective observational multicenter study. Cohort A includes metastatic patients in oligoprogression to ICI maintaining the same ICI due to clinical benefit and who receive concomitant SABR. B is a comparative group of oligometastatic patients receiving only SABR. Blood samples are extracted at baseline (T1), after the first (T2) and last (T3) fraction, two months post-SABR (T4) and at further progression (TP). Response is evaluated by iRECIST and defined by the objective response rate (ORR)—complete and partial responses. We assess peripheral blood mononuclear cells (PBMCs), circulating cell-free DNA (cfDNA) and small RNA from extracellular vesicles. Twenty-seven patients could be analyzed (cohort A: n = 19; B: n = 8). Most were males with non-small cell lung cancer and one progressing lesion. With a median follow-up of 6 months, the last ORR was 63% (26% complete and 37% partial response). A decrease in cfDNA from T2 to T3 correlated with a good response. At T2, CD8+PD1+ and CD8+PDL1+ cells were increased in non-responders and responders, respectively. At T2, 27 microRNAs were differentially expressed. These are potential biomarkers of response to I-SABR in oligoprogressive disease. Full article
(This article belongs to the Special Issue Precision Medicine in Oncology 2.0)
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17 pages, 2088 KiB  
Article
Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer
by Janine Soares, Mariana Eiras, Dylan Ferreira, Daniela A. R. Santos, Marta Relvas-Santos, Beatriz Santos, Martina Gonçalves, Eduardo Ferreira, Renata Vieira, Luís Pedro Afonso, Lúcio Lara Santos, Mário Dinis-Ribeiro, Luís Lima and José Alexandre Ferreira
Int. J. Mol. Sci. 2024, 25(7), 3722; https://doi.org/10.3390/ijms25073722 - 27 Mar 2024
Cited by 1 | Viewed by 1622
Abstract
Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute [...] Read more.
Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen—a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection. Full article
(This article belongs to the Special Issue Precision Medicine in Oncology 2.0)
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14 pages, 3009 KiB  
Communication
Aberrantly Glycosylated GLUT1 as a Poor Prognosis Marker in Aggressive Bladder Cancer
by Eduardo Ferreira, Dylan Ferreira, Marta Relvas-Santos, Rui Freitas, Janine Soares, Rita Azevedo, Luís Pedro Afonso, Luís Lima, Beatriz Santos, Martina Gonçalves, André M. N. Silva, Lúcio Lara Santos, Andreia Peixoto and José Alexandre Ferreira
Int. J. Mol. Sci. 2024, 25(6), 3462; https://doi.org/10.3390/ijms25063462 - 19 Mar 2024
Viewed by 1533
Abstract
Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 [...] Read more.
Muscle-invasive bladder cancer (MIBC) remains a pressing health concern due to conventional treatment failure and significant molecular heterogeneity, hampering the development of novel targeted therapeutics. In our quest for novel targetable markers, recent glycoproteomics and bioinformatics data have pinpointed (glucose transporter 1) GLUT1 as a potential biomarker due to its increased expression in tumours compared to healthy tissues. This study explores this hypothesis in more detail, with emphasis on GLUT1 glycosylation patterns and cancer specificity. Immunohistochemistry analysis across a diverse set of human bladder tumours representing all disease stages revealed increasing GLUT1 expression with lesion severity, extending to metastasis, while remaining undetectable in healthy urothelium. In line with this, GLUT1 emerged as a marker of reduced overall survival. Revisiting nanoLC-EThcD-MS/MS data targeting immature O-glycosylation on muscle-invasive tumours identified GLUT1 as a carrier of short glycosylation associated with invasive disease. Precise glycosite mapping uncovered significant heterogeneity between patient samples, but also common glycopatterns that could provide the molecular basis for targeted solutions. Immature O-glycosylation conferred cancer specificity to GLUT1, laying the molecular groundwork for enhanced targeted therapeutics in bladder cancer. Future studies should focus on a comprehensive mapping of GLUT1 glycosites for highly specific cancer-targeted therapy development for bladder cancer. Full article
(This article belongs to the Special Issue Precision Medicine in Oncology 2.0)
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10 pages, 698 KiB  
Opinion
Companion Tests and Personalized Cancer Therapy: Reaching a Glass Ceiling
by Victoria Ferrari, Baharia Mograbi, Jocelyn Gal and Gérard Milano
Int. J. Mol. Sci. 2024, 25(18), 9991; https://doi.org/10.3390/ijms25189991 - 17 Sep 2024
Viewed by 1554
Abstract
The use of companion diagnostics has become a standard in precision oncology in the context of ongoing therapeutic innovation. However, certain limitations make their application imperfect in current practice. This position paper underscores the need to broaden the notion of companion testing, considering [...] Read more.
The use of companion diagnostics has become a standard in precision oncology in the context of ongoing therapeutic innovation. However, certain limitations make their application imperfect in current practice. This position paper underscores the need to broaden the notion of companion testing, considering the potential of emerging technologies, including computational biology, to overcome these limitations. This wave of progress should impact not only our representation of the analytical tool itself but also the nature of the tumoral sample under analysis (liquid biopsies). The complex inter-relationship between companion test guided-personalized therapy, and health agency policies for new drug agreements will also be discussed. Full article
(This article belongs to the Special Issue Precision Medicine in Oncology 2.0)
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