Cancer biology is a multidisciplinary field that continues to confront formidable challenges, with cancer ranking as a principal cause of global morbidity and mortality. Despite notable progress in diagnostics and targeted therapeutics, predictions indicate a growing burden of cancer, fueled by resistance to therapies and sophisticated mechanisms of immune evasion. These hurdles are amplified by the complexity of molecular events that propel tumor initiation, progression, and the recurrence that so often undermines long-term treatment responses. Among these molecular regulators, post-translational modifications (PTMs) have emerged as vital orchestrators of cancer cell behavior. While canonical PTMs -such as phosphorylation, ubiquitination, and acetylation- have long been studied, recent advances have illuminated a vast chemical diversity of modifications and their interplay, defining novel “PTM codes” that shape oncogenic phenotypes and clinical outcomes.

Current research highlights that the dynamic and context-dependent regulation of PTMs (over 400 distinct PTMs catalogued to date) fundamentally influences virtually every aspect of cancer biology, from tumorigenesis to metastatic dissemination, immune modulation, and therapy resistance. Recent discoveries, including unconventional modifications like UFMylation, malonylation, ISGylation, lactylation, crotonylation, serotonylation, propionylation, butyrylation, citrullination, and the bacterial process of deazaguanylation, underscore a rapidly expanding PTM repertoire and suggest untapped regulatory potential in mammals. State-of-the-art multi-omics and computational methods are decoding intricate PTM networks and their crosstalk, revealing how dysregulation disrupts homeostatic signaling and drives cancer progression and resistance to therapy. Novel therapeutics targeting PTM enzymes, such as kinase inhibitors or PROTACs, have provided proof-of-concept for PTM-centric drug development. However, these advances are shadowed by off-target toxicities and incomplete knowledge about modification context and substrate specificity.

This Research Topic aims to deepen the understanding of how diverse post-translational modifications govern cancer progression, immune escape, and resistance to therapy. By integrating mechanistic insights, systems-level analyses, and translational research, we seek to chart new directions for decoding PTM-mediated regulation in oncology. The overarching goal is to leverage multifaceted knowledge of PTMs -from classical to emerging types- to identify actionable mechanisms and refine therapeutic strategies for improved cancer management, with particular interest in the role of unconventional PTMs and their impact on cancer cell fate and treatment response.

This Research Topic is focused on elucidating the molecular and functional landscape of PTMs in human cancers, including their therapeutic targeting and translational potential, while primarily excluding investigations outside oncology or general reviews unrelated to PTM biology. To gather further insights in this area, we welcome articles addressing, but not limited to, the following themes:

- Molecular mechanisms and crosstalk of canonical and unconventional PTMs driving oncogenesis and metastasis

- Regulation of cancer hallmarks through PTM-mediated processes

- PTM-driven immune evasion and modulation of anti-tumor immunity

- Adaptive stress-response and signaling pathways regulated by PTMs under therapeutic stress

- Mechanisms by which PTM dynamics influence therapy response and resistance across treatment modalities

- Integrated multi-omics and computational approaches to dissect PTM networks in cancer

- Therapeutic targeting of PTM-modifying enzymes and development of PTM-based anticancer agents

- Clinical translation and toxicity management for PTM-targeted therapies

- Synergistic combination strategies employing PTM-focused agents alongside conventional cancer therapies

Are you interested in contributing a manuscript to this Research Topic?

Decoding Post-Translational Modifications in Cancer Progression, Immune Response, and Therapy Resistance