Class 2 Tumor Suppressor Gene Pathways for Therapeutic Applications in Hard-to-Treat Cancers

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 2199

Special Issue Editor


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Guest Editor
Institute of Pathology, Medical Faculty, RWTH Aachen University, D-52074 Aachen, Germany
Interests: class 2 tumor suppressor genes; epigenetic therapies; drug development for personalized cancer treatment; tumor suppressor mimetics

Special Issue Information

Dear Colleagues,

Hard-to-treat (HTT) cancers are a group of malignant tumors that are difficult to treat with conventional cancer treatments such as surgery, chemotherapy or radiotherapy. These cancers are typically more advanced or aggressive and are more likely to recur after treatment, resulting in poor prognosis. Examples of HTT cancers are pancreatic cancer, liver cancer, ovarian cancer, brain tumors, esophageal cancer and some types of blood cancer, such as multiple myeloma. However, some cancer subtypes, such as basal-type breast and bladder cancers, can be considered as HTT cancers as well, since they are associated with aggressive diseases and unfavorable survival.

Furthermore, many HTT cancers are known to be difficult to treat effectively with targeted therapies based on driver alterations such as oncogenic mutations or gene fusions. In contrast to non-small cell lung cancer (NSCLC), a prime example of a tumor entity with efficiently treatable drivers, HTT cancers are often not efficiently treatable with these approaches.

This Special Issue will investigate to what extent the challenging treatment of HTT tumors could be complemented by epigenetic cancer therapies in the future. The focus will be on new approaches resulting from the understanding of epigenetic signaling pathways in the cancer cell. Of particular relevance here are class 2 tumor suppressor genes, which are silenced in tumors at the level of promoter DNA methylation. The Special Issue is intended to contribute to finding new ideas and starting points for the epigenetic therapy of HTT cancers. A first concept for this strategy has already been published by the Guest Editor recently: https://www.mdpi.com/2072-6694/14/18/4386.

Prof. Dr. Edgar Dahl
Guest Editor

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Keywords

  • hard-to-treat cancers
  • HTT cancers
  • class 2 tumor suppressor genes
  • C2TSGs
  • DNA methylation driver
  • DNAme driver
  • epigenetic therapies
  • cancer drug development
  • personalized cancer therapy
  • tumor suppressor mimetics

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Published Papers (2 papers)

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Research

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16 pages, 3244 KiB  
Article
High Expression of the Tumor Suppressor Protein ITIH5 in Cholangiocarcinomas Correlates with a Favorable Prognosis
by Verena J. Dreyer, Jia-Xin Shi, Michael Rose, Maureen T. Onyuro, Florian Steib, Lars Hilgers, Lancelot Seillier, Jana Dietrich, Janik Riese, Steffen K. Meurer, Ralf Weiskirchen, Ulf Neumann, Lara Heij, Tom Luedde, Sven H. Loosen, Isabella Lurje, Georg Lurje, Nadine T. Gaisa, Danny Jonigk, Jan Bednarsch, Edgar Dahl and Nadina Ortiz Brüchleadd Show full author list remove Hide full author list
Cancers 2024, 16(21), 3647; https://doi.org/10.3390/cancers16213647 - 29 Oct 2024
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Abstract
Background/Objectives: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene ITIH5, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of [...] Read more.
Background/Objectives: Cholangiocarcinoma (CCA) are aggressive bile duct cancers with a poor prognosis for which there are only few established prognostic biomarkers and molecular targets available. The gene ITIH5, a known class II tumor suppressor gene (C2TSG), encodes a secreted protein of the extracellular matrix mediating tumor suppressive properties. Recently, it was surprisingly found that the ITIH5 protein is specifically upregulated in CCAs and that ITIH5 detection in blood could be an excellent liquid biopsy marker for indicating the presence of a CCA tumor in a patient. We therefore investigated whether patients with CCAs with abundant versus low ITIH5 protein expression also differ in their prognosis. Methods: To clarify this question, a large CCA cohort (n = 175) was examined using immunohistochemistry on a tissue microarray (TMA). Results: Abundant ITIH5 expression in CCA was associated with favorable survival, a low UICC stage and the absence of perineural invasion (PNI). Conclusions: ITIH5 has biomarker potential not only for the early detection of CCA from blood-based liquid biopsies but also as a prognostic tissue biomarker for risk stratification. Our results suggest that the upregulation of ITIH5 is particularly abundant in intrahepatic CCAs (iCCA). The mechanisms mediating the strong initial upregulation of ITIH5 during the oncogenic transformation of bile duct cells are still unclear. Full article
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Review

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12 pages, 556 KiB  
Review
Epigenetic Therapies in Triple-Negative Breast Cancer: Concepts, Visions, and Challenges
by Ulrich Lehmann
Cancers 2024, 16(12), 2164; https://doi.org/10.3390/cancers16122164 - 7 Jun 2024
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Abstract
Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer is defined by the absence of hormone receptor and growth factor receptor ERBB2/HER2 expression. It is characterized by a more aggressive course of [...] Read more.
Breast cancer, the most frequent malignancy in women worldwide, is a molecularly and clinically very heterogeneous disease. Triple-negative breast cancer is defined by the absence of hormone receptor and growth factor receptor ERBB2/HER2 expression. It is characterized by a more aggressive course of disease and a shortage of effective therapeutic approaches. Hallmarks of cancer cells are not only genetic alterations, but also epigenetic aberrations. The most studied and best understood alterations are methylation of the DNA base cytosine and the covalent modification of histone proteins. The reversibility of these covalent modifications make them attractive targets for therapeutic intervention, as documented in numerous ongoing clinical trials. Epidrugs, targeting DNA methylation and histone modifications, might offer attractive new options in treating triple-negative breast cancer. Currently, the most promising options are combination therapies in which the epidrug increases the efficiency of immuncheckpoint inhibitors. This review focusses exclusively on DNA methylation and histone modifications. In reviewing the knowledge about epigenetic therapies in breast cancer, and especially triple-negative breast cancer, the focus is on explaining concepts and raising awareness of what is not yet known and what has to be clarified in the future. Full article
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