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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 2023) | Viewed by 25185

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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
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Special Issue Information

Dear Colleagues,

Precision medicine in oncology is considered an emergent approach to cancer treatment and prevention that considers individual variability in genes, the environment, and lifestyle for each person. 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 susceptibility to a disease, the biology or prognosis of diseases they may develop, or their reaction to a certain therapy. Preventive or therapeutic actions can thus be focused on individuals who will benefit, saving money and reducing adverse effects.

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

Investigations into a myriad of fields such as biomarker discovery, “omics” approaches, such as pharmacogenomics, proteomics, genomics, and transcriptomics, or big data analysis are welcome. Works that help decipher molecular changes and identify 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

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Keywords

precision oncology
biomarkers
data analysis
multiomics
patient stratification
molecular profilimg
targeted therateutics
immunotherapy

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Published Papers (9 papers)

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Research

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26 pages, 9530 KiB

Open AccessArticle

Construction and Validation of a Reliable Disulfidptosis-Related LncRNAs Signature of the Subtype, Prognostic, and Immune Landscape in Colon Cancer

by Xiaoqian Dong, Pan Liao, Xiaotong Liu, Zhenni Yang, Yali Wang, Weilong Zhong and Bangmao Wang

Int. J. Mol. Sci. 2023, 24(16), 12915; https://doi.org/10.3390/ijms241612915 - 18 Aug 2023

Cited by 12 | Viewed by 2632

Abstract

Disulfidptosis, a novel form of regulated cell death (RCD) associated with metabolism, represents a promising intervention target in cancer therapy. While abnormal lncRNA expression is associated with colon cancer development, the prognostic potential and biological characteristics of disulfidptosis-related lncRNAs (DRLs) remain unclear. Consequently, the research aimed to discover a novel indication of DRLs with significant prognostic implications, and to investigate their possible molecular role in the advancement of colon cancer. Here, we acquired RNA-seq data, pertinent clinical data, and genomic mutations of colon adenocarcinoma (COAD) from the TCGA database, and then DRLs were determined through Pearson correlation analysis. A total of 434 COAD patients were divided in to three subgroups through clustering analysis based on DRLs. By utilizing univariate Cox regression, the least absolute shrinkage and selection operator (LASSO) algorithm, and multivariate Cox regression analysis, we ultimately created a prognostic model consisting of four DRLs (AC007728.3, AP003555.1, ATP2B1.AS1, and NSMCE1.DT), and an external database was used to validate the prognostic features of the risk model. According to the Kaplan–Meier curve analysis, patients in the low-risk group exhibited a considerably superior survival time in comparison to those in the high-risk group. Enrichment analysis revealed a significant association between metabolic processes and the genes that were differentially expressed in the high- and low-risk groups. Additionally, significant differences in the tumor immune microenvironment landscape were observed, specifically pertaining to immune cells, function, and checkpoints. High-risk patients exhibited a low likelihood of immune evasion, as indicated by the Tumor Immune Dysfunction and Exclusion (TIDE) analysis. Patients who exhibit both a high risk and high Tumor Mutational Burden (TMB) experience the least amount of time for survival, whereas those belonging to the low-risk and low-TMB category demonstrate the most favorable prognosis. In addition, the risk groups determined by the 4-DRLs signature displayed distinct drug sensitivities. Finally, we confirmed the levels of expression for four DRLs through rt-qPCR in both tissue samples from colon cancer patients and cell lines. Taken together, the first 4-DRLs-based signature we proposed may serve for a hopeful instrument for forecasting the prognosis, immune landscape, and therapeutic responses in colon cancer patients, thereby facilitating optimal clinical decision-making. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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13 pages, 2276 KiB

Open AccessArticle

Immune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study

by E. Titmuss, K. Milne, M. R. Jones, T. Ng, J. T. Topham, S. D. Brown, D. F. Schaeffer, S. Kalloger, D. Wilson, R. D. Corbett, L. M. Williamson, K. Mungall, A. J. Mungall, R. A. Holt, B. H. Nelson, S. J. M. Jones, J. Laskin, H. J. Lim and M. A. Marra

Int. J. Mol. Sci. 2023, 24(6), 5869; https://doi.org/10.3390/ijms24065869 - 20 Mar 2023

Cited by 2 | Viewed by 2462 | Correction

Abstract

Colorectal cancers are one of the most prevalent tumour types worldwide and, despite the emergence of targeted and biologic therapies, have among the highest mortality rates. The Personalized OncoGenomics (POG) program at BC Cancer performs whole genome and transcriptome analysis (WGTA) to identify specific alterations in an individual’s cancer that may be most effectively targeted. Informed using WGTA, a patient with advanced mismatch repair-deficient colorectal cancer was treated with the antihypertensive drug irbesartan and experienced a profound and durable response. We describe the subsequent relapse of this patient and potential mechanisms of response using WGTA and multiplex immunohistochemistry (m-IHC) profiling of biopsies before and after treatment from the same metastatic site of the L3 spine. We did not observe marked differences in the genomic landscape before and after treatment. Analyses revealed an increase in immune signalling and infiltrating immune cells, particularly CD8+ T cells, in the relapsed tumour. These results indicate that the observed anti-tumour response to irbesartan may have been due to an activated immune response. Determining whether there may be other cancer contexts in which irbesartan may be similarly valuable will require additional studies. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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20 pages, 3425 KiB

Open AccessArticle

Evaluating the Expression and Prognostic Value of Genes Encoding Microtubule-Associated Proteins in Lung Cancer

by Natsaranyatron Singharajkomron, Varalee Yodsurang, Suthasinee Seephan, Sakkarin Kungsukool, Supinda Petchjorm, Nara Maneeganjanasing, Warunyu Promboon, Wadsana Dangwilailuck and Varisa Pongrakhananon

Int. J. Mol. Sci. 2022, 23(23), 14724; https://doi.org/10.3390/ijms232314724 - 25 Nov 2022

Cited by 6 | Viewed by 2762

Abstract

Microtubule-associated proteins (MAPs) play essential roles in cancer development. This study aimed to identify transcriptomic biomarkers among MAP genes for the diagnosis and prognosis of lung cancer by analyzing differential gene expressions and correlations with tumor progression. Gene expression data of patients with lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) from the Cancer Genome Atlas (TCGA) database were used to identify differentially expressed MAP genes (DEMGs). Their prognostic value was evaluated by Kaplan–Meier and Cox regression analysis. Moreover, the relationships between alterations in lung cancer hallmark genes and the expression levels of DEMGs were investigated. The candidate biomarker genes were validated using three independent datasets from the Gene Expression Omnibus (GEO) database and by quantitative reverse transcription polymerase chain reaction (qRT-PCR) on clinical samples. A total of 88 DEMGs were identified from TCGA data. The 20 that showed the highest differential expression were subjected to association analysis with hallmark genes. Genetic alterations in TP53, EGFR, PTEN, NTRK1, and PIK3CA correlated with the expression of most of these DEMGs. Of these, six candidates—NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2—were significantly differentially expressed and correlated with the overall survival (OS) of the patients. The mRNA expression profiles of these candidates were consistently verified using three GEO datasets and qRT-PCR on patient lung tissues. The expression levels of NUF2, KIF4A, KIF18B, DLGAP5, NEK2, and LRRK2 can serve as diagnostic biomarkers for LUAD and LUSC. Moreover, the first five can serve as prognostic biomarkers for LUAD, while LRRK2 can be a prognostic biomarker for LUSC. Our research describes the novel role and potential application of MAP-encoding genes in clinical practice. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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14 pages, 4890 KiB

Open AccessArticle

A Comprehensive Prognostic Analysis of Tumor-Related Blood Group Antigens in Pan-Cancers Suggests That SEMA7A as a Novel Biomarker in Kidney Renal Clear Cell Carcinoma

by Yange Wang, Chenyang Li, Xinlei Qi, Yafei Yao, Lu Zhang, Guosen Zhang, Longxiang Xie, Qiang Wang, Wan Zhu and Xiangqian Guo

Int. J. Mol. Sci. 2022, 23(15), 8799; https://doi.org/10.3390/ijms23158799 - 8 Aug 2022

Cited by 4 | Viewed by 2139

Abstract

Blood group antigen is a class of heritable antigenic substances present on the erythrocyte membrane. However, the role of blood group antigens in cancer prognosis is still largely unclear. In this study, we investigated the expression of 33 blood group antigen genes and their association with the prognosis of 30 types of cancers in 31,870 tumor tissue samples. Our results revealed that blood group antigens are abnormally expressed in a variety of cancers. The high expression of these antigen genes was mainly related to the activation of the epithelial-mesenchymal transition (EMT) pathway. High expression of seven antigen genes, i.e., FUT7, AQP1, P1, C4A, AQP3, KEL and DARC, were significantly associated with good OS (Overall Survival) in six types of cancers, while ten genes, i.e., AQP1, P1, C4A, AQP3, BSG, CD44, CD151, LU, FUT2, and SEMA7A, were associated with poor OS in three types of cancers. Kidney renal clear cell carcinoma (KIRC) is associated with the largest number (14 genes) of prognostic antigen genes, i.e., CD44, CD151, SEMA7A, FUT7, CR1, AQP1, GYPA, FUT3, FUT6, FUT1, SLC14A1, ERMAP, C4A, and B3GALT3. High expression of SEMA7A gene was significantly correlated with a poor prognosis of KIRC in this analysis but has not been reported previously. SEMA7A might be a putative biomarker for poor prognosis in KIRC. In conclusion, our analysis indicates that blood group antigens may play functional important roles in tumorigenesis, progression, and especially prognosis. These results provide data to support prognostic marker development and future clinical management. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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Review

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21 pages, 1566 KiB

Open AccessReview

Advancing Craniopharyngioma Management: A Systematic Review of Current Targeted Therapies and Future Perspectives

by Edoardo Agosti, Marco Zeppieri, Sara Antonietti, Amedeo Piazza, Tamara Ius, Marco Maria Fontanella, Alessandro Fiorindi and Pier Paolo Panciani

Int. J. Mol. Sci. 2024, 25(2), 723; https://doi.org/10.3390/ijms25020723 - 5 Jan 2024

Cited by 3 | Viewed by 3068

Abstract

Craniopharyngiomas present unique challenges in surgical management due to their proximity to critical neurovascular structures. This systematic review investigates genetic and immunological markers as potential targets for therapy in craniopharyngiomas, assessing their involvement in tumorigenesis, and their influence on prognosis and treatment strategies. The systematic review adhered to PRISMA guidelines, with a thorough literature search conducted on PubMed, Ovid MED-LINE, and Ovid EMBASE. Employing MeSH terms and Boolean operators, the search focused on craniopharyngiomas, targeted or molecular therapy, and clinical outcomes or adverse events. Inclusion criteria encompassed English language studies, clinical trials (randomized or non-randomized), and investigations into adamantinomatous or papillary craniopharyngiomas. Targeted therapies, either standalone or combined with chemotherapy and/or radiotherapy, were examined if they included clinical outcomes or adverse event analysis. Primary outcomes assessed disease response through follow-up MRI scans, categorizing responses as follows: complete response (CR), near-complete response (NCR), partial response, and stable or progressive disease based on lesion regression percentages. Secondary outcomes included treatment type and duration, as well as adverse events. A total of 891 papers were initially identified, of which 26 studies spanning from 2000 to 2023 were finally included in the review. Two tables highlighted adamantinomatous and papillary craniopharyngiomas, encompassing 7 and 19 studies, respectively. For adamantinomatous craniopharyngiomas, Interferon-2α was the predominant targeted therapy (29%), whereas dabrafenib took precedence (70%) for papillary craniopharyngiomas. Treatment durations varied, ranging from 1.7 to 28 months. Positive responses, including CR or NCR, were observed in both types of craniopharyngiomas (29% CR for adamantinomatous; 32% CR for papillary). Adverse events, such as constitutional symptoms and skin changes, were reported, emphasizing the need for vigilant monitoring and personalized management to enhance treatment tolerability. Overall, the data highlighted a diverse landscape of targeted therapies with encouraging responses and manageable adverse events, underscoring the importance of ongoing research and individualized patient care in the exploration of treatment options for craniopharyngiomas. In the realm of targeted therapies for craniopharyngiomas, tocilizumab and dabrafenib emerged as prominent choices for adamantinomatous and papillary cases, respectively. While adverse events were common, their manageable nature underscored the importance of vigilant monitoring and personalized management. Acknowledging limitations, future research should prioritize larger, well-designed clinical trials and standardized treatment protocols to enhance our understanding of the impact of targeted therapies on craniopharyngioma patients. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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18 pages, 1602 KiB

Open AccessReview

The Future of Precision Oncology

by Stuart L. Rulten, Richard P. Grose, Susanne A. Gatz, J. Louise Jones and Angus J. M. Cameron

Int. J. Mol. Sci. 2023, 24(16), 12613; https://doi.org/10.3390/ijms241612613 - 9 Aug 2023

Cited by 10 | Viewed by 5412

Abstract

Our understanding of the molecular mechanisms underlying cancer development and evolution have evolved rapidly over recent years, and the variation from one patient to another is now widely recognized. Consequently, one-size-fits-all approaches to the treatment of cancer have been superseded by precision medicines that target specific disease characteristics, promising maximum clinical efficacy, minimal safety concerns, and reduced economic burden. While precision oncology has been very successful in the treatment of some tumors with specific characteristics, a large number of patients do not yet have access to precision medicines for their disease. The success of next-generation precision oncology depends on the discovery of new actionable disease characteristics, rapid, accurate, and comprehensive diagnosis of complex phenotypes within each patient, novel clinical trial designs with improved response rates, and worldwide access to novel targeted anticancer therapies for all patients. This review outlines some of the current technological trends, and highlights some of the complex multidisciplinary efforts that are underway to ensure that many more patients with cancer will be able to benefit from precision oncology in the near future. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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23 pages, 5934 KiB

Open AccessReview

MicroRNA Biomarkers as Promising Tools for Early Colorectal Cancer Screening—A Comprehensive Review

by Daniela A. R. Santos, Cristiana Gaiteiro, Marlene Santos, Lúcio Santos, Mário Dinis-Ribeiro and Luís Lima

Int. J. Mol. Sci. 2023, 24(13), 11023; https://doi.org/10.3390/ijms241311023 - 3 Jul 2023

Cited by 10 | Viewed by 2957

Abstract

Colorectal cancer (CRC) ranks as the third most prevalent cancer worldwide. Early detection of this neoplasia has proven to improve prognosis, resulting in a 90% increase in survival. However, available CRC screening methods have limitations, requiring the development of new tools. MicroRNA biomarkers have emerged as a powerful screening tool, as they are highly expressed in CRC patients and easily detectable in several biological samples. While microRNAs are extensively studied in blood samples, recent interest has now arisen in other samples, such as stool samples, where they can be combined with existing screening methods. Among the microRNAs described in the literature, microRNA-21-5p and microRNA-92a-3p and their cluster have demonstrated high potential for early CRC screening. Furthermore, the combination of multiple microRNAs has shown improved performance in CRC detection compared to individual microRNAs. This review aims to assess the available data in the literature on microRNAs as promising biomarkers for early CRC screening, explore their advantages and disadvantages, and discuss the optimal study characteristics for analyzing these biomarkers. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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18 pages, 1913 KiB

Open AccessReview

New Approaches in Early-Stage NSCL Management: Potential Use of PARP Inhibitors and Immunotherapy Combination

by Marta Pina Fernandes, Cristina Oliveira, Hugo Sousa and Júlio Oliveira

Int. J. Mol. Sci. 2023, 24(4), 4044; https://doi.org/10.3390/ijms24044044 - 17 Feb 2023

Cited by 2 | Viewed by 2442

Abstract

Lung cancer is the second most common cancer in the world, being the first cause of cancer-related mortality. Surgery remains the only potentially curative treatment for Non-Small Cell Lung Cancer (NSCLC), but the recurrence risk remains high (30–55%) and Overall Survival (OS) is still lower than desirable (63% at 5 years), even with adjuvant treatment. Neoadjuvant treatment can be helpful and new therapies and pharmacologic associations are being studied. Immune Checkpoint Inhibitors (ICI) and PARP inhibitors (PARPi) are two pharmacological classes already in use to treat several cancers. Some pre-clinical studies have shown that its association can be synergic and this is being studied in different settings. Here, we review the PARPi and ICI strategies in cancer management and the information will be used to develop a clinical trial to evaluate the potential of PARPi association with ICI in early-stage neoadjuvant setting NSCLC. Full article

(This article belongs to the Special Issue Precision Medicine in Oncology)

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1 pages, 150 KiB

Open AccessCorrection

Correction: Titmuss et al. Immune Activation Following Irbesartan Treatment in a Colorectal Cancer Patient: A Case Study. Int. J. Mol. Sci. 2023, 24, 5869

Int. J. Mol. Sci. 2024, 25(22), 12225; https://doi.org/10.3390/ijms252212225 - 14 Nov 2024

Viewed by 172

Abstract

The journal’s Editorial Office and Editorial Board are jointly issuing a resolution and removal of the Journal Notice linked to this article [...] Full article

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