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Hallmarks of Cancer: Emerging Insights and Innovations
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Hallmarks of Cancer: Emerging Insights and Innovations

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 25 November 2025 | Viewed by 2617

Special Issue Editor

Dr. Konstantinos Syrigos

E-Mail Website
Guest Editor
Third Department of Internal Medicine, Sotiria Hospital, National and Kapodistrian University of Athens, School of Medicine, 11527 Athens, Greece
Interests: cancer; lung cancer; immunotherapy; immune-related adverse events
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The evolving landscape of cancer research continuously unveils new mechanisms and pathways that contribute to tumor development and progression. This Special Issue, 'Hallmarks of Cancer: Emerging Insights and Innovations', aims to capture the forefront of cancer research by highlighting novel molecular insights and innovative therapeutic strategies. It seeks to gather contributions that explore the emerging molecular hallmarks of cancer, advancements in genetic and epigenetic studies, breakthroughs in targeted therapy, and innovative diagnostic techniques. Our goal is to provide a comprehensive update that can serve as a resource for researchers and clinicians alike, fostering developments that could lead to improved patient outcomes.]

Dr. Konstantinos Syrigos
Guest Editor

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Keywords

  • proliferative signaling
  • growth suppression evasion
  • epigenetic reprogramming
  • immune system evasion
  • replicative immortality
  • inflammation and cancer
  • microbiome and cancer
  • invasion and metastasis
  • tumor microenvironment
  • cellular senescence
  • genomic instability
  • metabolic reprogramming
  • therapeutic resistance
  • molecular diagnostics
  • targeted cancer therapy

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Published Papers (2 papers)

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21 pages, 5787 KiB  
Article
Only Infant MLL-Rearranged Leukemia Is Susceptible to an Inhibition of Polo-like Kinase 1 (PLK-1) by Volasertib
by Jacqueline Fischer, Estelle Erkner, Pia Radszuweit, Thomas Hentrich, Hildegard Keppeler, Fulya Korkmaz, Julia Schulze-Hentrich, Rahel Fitzel, Claudia Lengerke, Dominik Schneidawind and Corina Schneidawind
Int. J. Mol. Sci. 2024, 25(23), 12760; https://doi.org/10.3390/ijms252312760 - 27 Nov 2024
Viewed by 987
Abstract
MLL-rearranged (MLLr) leukemia is characterized by a poor prognosis. Depending on the cell of origin, it differs in the aggressiveness and therapy response. For instance, in adults, volasertib blocking Polo-like kinase 1 (PLK-1) exhibited limited success. Otherwise, PLK-1 characterizes an [...] Read more.
MLL-rearranged (MLLr) leukemia is characterized by a poor prognosis. Depending on the cell of origin, it differs in the aggressiveness and therapy response. For instance, in adults, volasertib blocking Polo-like kinase 1 (PLK-1) exhibited limited success. Otherwise, PLK-1 characterizes an infant MLLr signature, indicating potential sensitivity. By using our CRISPR/Cas9 MLLr model in CD34+ cells from human cord blood (huCB) and bone marrow (huBM) mimicking the infant and adult patient diseases, we were able to shed light on this phenomenon. The PLK-1 mRNA level was significantly increased in our huCB compared to the huBM model, which was underpinned by analyzing infant and adult MLLr leukemia patients. Importantly, the expression levels correlated with a functional response. Volasertib induced a significant dose-dependent decrease in proliferation and cell cycle arrest, most pronounced in the infant model. Mechanistically, upon volasertib treatment, we uncovered negative feedback only in the huBM model by compensatory upregulation of PLK-1 and related genes like AURKA involved in mitosis. Importantly, the poor response could be overcome by a combinatorial strategy with alisertib, an Aurora kinase A inhibitor. Our study emphasizes the importance of considering the cell of origin in therapeutic decision-making and provides the rationale for evaluating volasertib and alisertib in MLLr leukemia. Full article
(This article belongs to the Special Issue Hallmarks of Cancer: Emerging Insights and Innovations)
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6 pages, 751 KiB  
Case Report
Atypical B-Cell Acute Lymphoblastic Leukemia with iAMP21 in the Context of Constitutional Ring Chromosome 21: A Case Report and Review of the Genetic Insights
by José Vicente Gil, Gayane Avetisyan, Sandra de las Heras, Alberto Miralles, María del Cañizo, Ángela Rico, María Eli Valerio, Vanesa Díaz, Paula Piñero, Carmen Orellana, José Cervera, Carolina Fuentes, José María Fernández, Eva Barragán, Esperanza Such and Marta Llop
Int. J. Mol. Sci. 2025, 26(1), 357; https://doi.org/10.3390/ijms26010357 - 3 Jan 2025
Viewed by 1161
Abstract
Recent studies have demonstrated the association between constitutional ring chromosome 21 (r(21)c) and the development of B-cell acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21). iAMP21 acts as a driver which is often accompanied by secondary alterations that influence disease [...] Read more.
Recent studies have demonstrated the association between constitutional ring chromosome 21 (r(21)c) and the development of B-cell acute lymphoblastic leukemia (B-ALL) with intrachromosomal amplification of chromosome 21 (iAMP21). iAMP21 acts as a driver which is often accompanied by secondary alterations that influence disease progression. Here, we report an atypical case of iAMP21 B-ALL with a unique molecular profile in the context of r(21)c. The onset of B-ALL occurred significantly earlier than previously reported in iAMP21-ALL, likely due to the presence of r(21)c. Only scarce cases of iAMP21 with concomitant PAX5 fusions have been reported. Through an extensive genomic characterization, the novel WWOX::PAX5 as well as 13q12.2 deletion involving FLT3 overexpression was found. These findings suggest that r(21)c may induce chromosomal instability on chromosome 21, triggering chromothripsis and leading to iAMP21-ALL. This case provides valuable insights to unravel the complex interplay between germline and somatic genetic alterations in leukemia. Moreover, it underscores the need for thorough genetic evaluation and multidisciplinary management in patients with syndromic presentation, particularly when rare genetic events may contribute to hematologic malignancies. Full article
(This article belongs to the Special Issue Hallmarks of Cancer: Emerging Insights and Innovations)
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