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Ongoing Anticancer Agents

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: 20 December 2025 | Viewed by 1665

Special Issue Editor


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Guest Editor
Department of Pharmacy-Drug Sciences, University of Bari “Aldo Moro”, Via E. Orabona 4, I-70125 Bari, Italy
Interests: anticancer drugs; phenotypic drug discovery; tumor cell biology; tumor microenvironment; inflammation
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Special Issue Information

Dear Colleagues,

Tumorigenesis, arguably the most intricate pathological process, arises from the progressive accumulation of genetic mutations over extended periods, ultimately leading to the gradual disruption of homeostatic mechanisms at the cellular, tissue, and organismal levels. Over recent decades, advances in understanding the molecular and cellular mechanisms underlying tumorigenesis have significantly influenced the development of anticancer therapies. Remarkably, since the early 2000s, the number of anticancer drugs approved for clinical application has increased from a few dozen to several hundred distinct agents.

In the effort to target the hallmarks of cancer—that is, the specific functional characteristics enabling cancer cells to survive, proliferate, and metastasize—numerous classes of anticancer drugs are currently undergoing rigorous investigation and development. This IJMS Special Issue, entitled Ongoing Anticancer Agents, aims to compile both experimental studies and review articles that reflect the complexity of the disease and highlight various aspects of the foundational research focused on therapeutic innovation.

Dr. Mauro Coluccia
Guest Editor

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Keywords

  • tumorigenesis
  • anticancer drugs
  • therapeutic innovation
  • platinum-based drugs
  • anticancer therapies

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Published Papers (2 papers)

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Research

15 pages, 2615 KB  
Article
Zongertinib, a Novel HER2 Tyrosine Kinase Inhibitor, Maintains an Anticancer Activity for Trastuzumab Deruxtecan-Resistant Cancers Harboring HER2-Overexpression
by Takashi Kurosaki, Shinichiro Suzuki, Kimio Yonesaka, Yusuke Kawanaka, Toshiyuki Takehara, Takeshi Teramura, Kazuko Sakai, Kazuto Nishio and Hidetoshi Hayashi
Int. J. Mol. Sci. 2025, 26(21), 10515; https://doi.org/10.3390/ijms262110515 - 29 Oct 2025
Viewed by 843
Abstract
Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate comprising trastuzumab linked to a payload DXd, has been extensively used to treat various cancers harboring HER2 overexpression. However, resistance development has been a major challenge to T-DXd treatment. To explore treatment strategies for T-DXd-resistant cancers, we [...] Read more.
Trastuzumab deruxtecan (T-DXd), an antibody–drug conjugate comprising trastuzumab linked to a payload DXd, has been extensively used to treat various cancers harboring HER2 overexpression. However, resistance development has been a major challenge to T-DXd treatment. To explore treatment strategies for T-DXd-resistant cancers, we examined two T-DXd-resistant cells named DSR32 and DSR4, which were obtained from HER2 gene-amplified H2170 lung cancer and N87 gastric cancer cells, respectively. The uptake of T-DXd and its transport to lysosomes in DSR32 cells were reduced. Subsequently, HER2 gene copy number (from 54 to 12) was reduced, which decreased HER2 expression on the cell surface. Thus, T-DXd-resistance might be observed due to the reduced T-DXd uptake caused by decreased HER2 expression in DSR32 cells. In DSR4 cells, no change was observed in HER2 expression and in the uptake and transport of T-DXd. The reduced linker cleavage activity may be associated with T-DXd resistance in DSR4 cells. Meanwhile, both DSR32 and DSR4 cells maintained HER2 activation; thus, zongertinib, a HER2-selective tyrosine kinase inhibitor, blocked the HER2 pathway, induced apoptosis, and inhibited colony formation. Overall, zongertinib can provide therapeutic relief to patients with HER2-overexpressing cancer who have developed resistance to T-DXd. Full article
(This article belongs to the Special Issue Ongoing Anticancer Agents)
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17 pages, 3434 KB  
Article
Ebselen Suppresses Breast Cancer Tumorigenesis by Inhibiting YTHDF1-Mediated c-Fos Expression
by Arathy Vasukutty, Poshan Yugal Bhattarai and Hong Seok Choi
Int. J. Mol. Sci. 2025, 26(19), 9416; https://doi.org/10.3390/ijms26199416 - 26 Sep 2025
Viewed by 677
Abstract
YTHDF1, an N6-methyladenosine (m6A)-binding protein, plays a key role in breast cancer progression, yet its therapeutic targeting remains underexplored. In this study, we investigated the anticancer effects of the novel YTHDF1 inhibitor ebselen in breast cancer cells. Ebselen treatment reduced cell [...] Read more.
YTHDF1, an N6-methyladenosine (m6A)-binding protein, plays a key role in breast cancer progression, yet its therapeutic targeting remains underexplored. In this study, we investigated the anticancer effects of the novel YTHDF1 inhibitor ebselen in breast cancer cells. Ebselen treatment reduced cell viability in a dose-dependent manner and induced apoptosis, as demonstrated by Annexin V staining, Sub-G1 accumulation, and DNA fragmentation. Consistently, ebselen increased reactive oxygen species (ROS) production and impaired autophagy induction. Mechanistically, ebselen impaired YTHDF1-mediated stabilization and translation of FOS mRNA, leading to decreased c-Fos expression. In addition, ebselen suppressed anchorage-independent growth in vitro and significantly reduced tumor growth in an orthotopic mouse model. These findings highlight YTHDF1 as a promising therapeutic target and support ebselen as a potential small-molecule inhibitor for breast cancer treatment. Full article
(This article belongs to the Special Issue Ongoing Anticancer Agents)
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