Advances in the Ubiquitin–Proteasome System (UPS) in Cancer Biology

Dear Colleagues,

The ubiquitin–proteasome system (UPS) plays a central role in nearly every aspect of cellular regulation, influencing protein stability, signaling networks, genome integrity, cell cycle progression, stress responses, and immune surveillance. Given its pervasive impact, it is no surprise that deregulation of UPS components contributes directly to tumor initiation, progression, metastasis, and therapeutic resistance. Recent advances in proteomics, structural biology, genome editing, and targeted therapeutics have opened new avenues for understanding how UPS components control cancer biology and how these pathways can be exploited for precision oncology.

This Special Issue of Cancers, titled “Advances in the Ubiquitin–Proteasome System (UPS) in Cancer Biology”, invites the submission of original research articles, comprehensive reviews, and perspective pieces addressing fundamental mechanisms as well as translational and clinical opportunities arising from UPS-focused cancer research. Our goal is to bring together cutting-edge studies that deepen our understanding of UPS dynamics in tumors and highlight innovative therapeutic strategies targeting ubiquitin signaling.

Topics of interest include but are not limited to the following.

• Mechanistic studies of UPS components in cancer:
  
  • Roles of E1, E2, and E3 ligases in tumorigenesis;
  • Functions of deubiquitinating enzymes (DUBs) in genome stability, DNA repair, apoptosis, or metabolism;
  • Ubiquitin-like modifiers (SUMO, NEDD8, ISG15) and their impact on cancer pathways.

• UPS in genome stability and DNA damage response:
  
  • Regulation of replication stress, DSB repair, checkpoint activation;
  • Proteostasis control of chromatin modifiers and DNA repair factors.

• UPS-mediated signaling pathways:
  
  • Crosstalk between ubiquitination and oncogenic pathways (e.g., MAPK, PI3K/AKT, WNT, NF-κB);
  • Ubiquitin-dependent control of immune signaling and tumor microenvironment interactions.
• Proteasome function and proteotoxic stress in cancer cells:
  
  • Mechanisms of proteasome regulation in cancer;
  • Adaptive responses to proteostasis imbalance and their therapeutic implications.
• UPS-targeted therapeutics and drug resistance:
  
  • Development of small-molecule inhibitors or molecular degraders (e.g., PROTACs, molecular glues);
  • Mechanisms of resistance to proteasome inhibitors and targeted UPS modulators;
  • UPS-based biomarkers for therapy response.
• Technological and systems biology approaches:
  • High-resolution proteomics and ubiquitinomics;
  • Structural and biophysical studies of ubiquitin ligases, DUBs, or proteasome subunits;
  • CRISPR-based screens revealing novel UPS cancer dependencies.

This Special Issue provides a focused platform for showcasing the most recent advancements connecting UPS biology to cancer mechanisms and treatment. We welcome contributions from molecular biologists, biochemists, structural biologists, translational scientists, and clinicians committed to advancing UPS-related cancer research.

We look forward to receiving your submissions and supporting the dissemination of high-impact, peer-reviewed research that will shape the future of UPS-targeted oncology.

Dr. Tarek A. Abbas
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 communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

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. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). 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.

• ubiquitin–proteasome system (UPS)
• cancer biology
• E3 ubiquitin ligases
• deubiquitinating enzymes (DUBs)
• protein degradation
• proteasome inhibitors
• ubiquitination signaling
• genome stability and DNA repair
• PROTACs and molecular glues
• targeted cancer therapeutics