Oncology ReviewsPub Date : 2025-05-06eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1567860
Mowei Kong, Yang Yu, Shuai Shao, Chunxiang Zhang
{"title":"Targeting mitochondrial ClpP: structural insights and therapeutic potential of ClpP agonists in cancer therapy.","authors":"Mowei Kong, Yang Yu, Shuai Shao, Chunxiang Zhang","doi":"10.3389/or.2025.1567860","DOIUrl":"10.3389/or.2025.1567860","url":null,"abstract":"<p><p>Mitochondrial \"powerhouses\" play a central function in cellular metabolism and energy generation. Their dysregulation is directly correlated with a myriad of diseases, among them cancer. The serine protease ClpP, accompanied by its cochaperone ClpX, is a principal homeostatic regulator in mitochondrial function by degrading aberrant proteins in order to preserve mitochondrial integrity. Recently, evidence suggests ClpP is overexpressed in many cancer cells and, as such, is an appealing target for drug therapy. In this review, current information about the structure, physiological function, and therapeutic promise of mitochondrial ClpP in oncology is summarized. We provide an overview about the mechanistic rationale behind ClpP agonists as novel anticancer drugs, their regulation in cell signal transduction, and the major challenge in the creation of small molecules that specifically activate human ClpP, but not bacterial ClpP. The review highlights the therapeutic promise of ClpP agonists as a novel approach in cancer therapy, presenting their prospective potential for cancer treatment by focusing on an unexplored mitochondrial target.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1567860"},"PeriodicalIF":3.1,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12089087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-05-01eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1567818
Wenshu Wang, Runyuan Zhao, Xi Liang, Manjun Liu, Haiyan Bai, Jianli Ge, Binxi Yao, Zheng Zhi, Jianming He
{"title":"Efficacies of radiotherapy in rectal cancer patients treated with total mesorectal excision or other types of surgery: an updated meta-analysis.","authors":"Wenshu Wang, Runyuan Zhao, Xi Liang, Manjun Liu, Haiyan Bai, Jianli Ge, Binxi Yao, Zheng Zhi, Jianming He","doi":"10.3389/or.2025.1567818","DOIUrl":"https://doi.org/10.3389/or.2025.1567818","url":null,"abstract":"<p><strong>Background: </strong>An updated meta-analysis was conducted to evaluate the efficacy of radiotherapy in rectal cancer patients treated with total mesorectal excision (TME) or other types of surgery (non-TME-only).</p><p><strong>Methods: </strong>The PubMed, Cochrane Library, and CNKI databases were searched. Data on overall survival (OS) were extracted.</p><p><strong>Results: </strong>Hazard ratios (HRs) for OS associated with preoperative radiotherapy, preoperative long-course concurrent chemoradiotherapy (LCCRT), preoperative radiotherapy alone, and postoperative radiotherapy in patients treated with TME were 1.02 [95% CI: 0.92-1.14, P = 0.65], 1.04 [95% CI: 0.93-1.16, P = 0.47], 0.87 [95% CI: 0.61-1.25, P = 0.46], and 1.18 [95% CI: 0.91-1.52, P = 0.20], respectively. HRs for OS associated with preoperative radiotherapy, preoperative LCCRT, preoperative radiotherapy alone, preoperative long-course RT (LCRT), and preoperative short-course radiotherapy (SCRT) in patients treated with non-TME-only surgery were 0.85 [95% CI: 0.79-0.90, P < 0.00001], 0.77 [95% CI: 0.63-0.94, P = 0.009], 0.86 [95% CI: 0.80-0.92, P < 0.0001], 0.83 [95% CI: 0.73-0.95, P = 0.005], and 0.84 [95% CI: 0.77-0.91, P= <0.0001], respectively. The HR for postoperative radiotherapy in patients treated with non-TME-only surgery was 1.08 [95% CI: 0.84-1.39, P = 0.57].</p><p><strong>Conclusion: </strong>Preoperative radiotherapy, regardless of the regimen, improves the OS in patients treated with non-TME-only surgery, but not in those treated with TME. Postoperative radiotherapy does not improve OS.</p><p><strong>Advances in knowledge: </strong>This meta-analysis will serve as a reference for decision-making in multidisciplinary approaches for rectal cancer patients.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1567818"},"PeriodicalIF":3.1,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078337/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-04-30eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1527742
Saskia Hazout, Christoph Oehler, Daniel R Zwahlen, Daniel Taussky
{"title":"Historical view of the effects of radiation on cancer cells.","authors":"Saskia Hazout, Christoph Oehler, Daniel R Zwahlen, Daniel Taussky","doi":"10.3389/or.2025.1527742","DOIUrl":"https://doi.org/10.3389/or.2025.1527742","url":null,"abstract":"<p><strong>Introduction: </strong>Since Röntgen's discovery of X-rays in 1895, advancements in radiobiology have significantly shaped radiotherapy practices. This historical review traces the evolution of radiobiological theories and their impacts on current therapeutic strategies.</p><p><strong>Materials and methods: </strong>Databases such as PubMed were utilized to trace the evolution of concepts in radiobiology.</p><p><strong>Results/discussion: </strong>One of the first theories concerning the effect of radiation was Dessauer's target theory, introduced in the 1920s. He found that damage to critical molecular cellular targets leads to cell death. In the early 20th century, Muller contributed to the understanding of DNA structure and radiation-induced mutations, highlighting theories on the impact of radiation on genetic material and cellular damage. In 1972, Kellerer and Rossi introduced the theory of dual radiation action, which explains that ionizing radiation induces sequential damage to DNA, starting with single-strand breaks and progressing to irreparable double-strand breaks. Recent advances have enhanced the understanding of the effects of radiation on the microenvironment and immune responses, thereby improving therapeutic outcomes. The significance of the sigmoid dose-response curve and the initial shoulder effect were recognized early, leading to theoretical models such as the multitarget single-hit, linear-quadratic and repair-misrepair models. The history of fractionation and the 4R/5R principles have informed today's ultrahigh fractionation techniques, including single doses of approximately 20 Gy.</p><p><strong>Conclusion: </strong>Although significant advances have been made toward understanding the effects of radiation on cancerous and healthy tissues, many clinical observations, such as the effects of very high doses or FLASH therapy, remain poorly understood.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1527742"},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-04-30eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1573797
Kaio Cezar Rodrigues Salum, Gabriel Brendo Alves Miranda, Alessandra Lima Dias, João Regis Ivar Carneiro, Patrícia Torres Bozza, Ana Carolina Proença da Fonseca, Tamara Silva
{"title":"The endocannabinoid system in cancer biology: a mini-review of mechanisms and therapeutic potential.","authors":"Kaio Cezar Rodrigues Salum, Gabriel Brendo Alves Miranda, Alessandra Lima Dias, João Regis Ivar Carneiro, Patrícia Torres Bozza, Ana Carolina Proença da Fonseca, Tamara Silva","doi":"10.3389/or.2025.1573797","DOIUrl":"https://doi.org/10.3389/or.2025.1573797","url":null,"abstract":"<p><p>The Endocannabinoid System (ECS) plays a critical role in maintaining physiological homeostasis, influencing a range of processes such as neuroprotection, inflammation, energy metabolism, and immune responses. Comprising cannabinoid receptors (CB1 and CB2), endogenous ligands (endocannabinoids), and the enzymes responsible for their synthesis and degradation, the ECS has attracted increasing attention in cancer research. Cannabinoid receptor activation has been associated with the regulation of cancer-related processes, including cell proliferation, apoptosis, and angiogenesis, suggesting that the ECS may have a role in tumor progression and cancer treatment. Preclinical studies have shown that cannabinoids, through their interaction with CB1 and CB2 receptors, can inhibit tumor cell growth, induce programmed cell death, and suppress the formation of new blood vessels in various cancer models. Despite these encouraging findings, the clinical translation of ECS-targeted therapies remains in its early stages. The complexity of tumor heterogeneity, the variability in patient responses, and the challenges associated with the pharmacokinetics of cannabinoids are significant obstacles to the broader application of these findings in clinical settings. This review provides an overview of the current understanding of the ECS's involvement in cancer biology, focusing on key mechanisms by which it may influence carcinogenesis. Additionally, we discuss the therapeutic potential of targeting the ECS in cancer treatment, while highlighting the limitations and uncertainties that need to be addressed through ongoing research.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1573797"},"PeriodicalIF":3.1,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075236/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144078815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects of engineered bacteria-assisted CAR T Cell therapy in gastrointestinal cancers.","authors":"Qingqing Zhang, Xiao Song, Junhong Liu, Xuejiao Zhou","doi":"10.3389/or.2025.1581856","DOIUrl":"https://doi.org/10.3389/or.2025.1581856","url":null,"abstract":"<p><p>The high incidence and mortality rates associated with gastrointestinal cancers represent a significant global health challenge. In recent years, CAR T cell therapy has emerged as a promising immunotherapeutic approach, demonstrating favorable clinical outcomes. However, the application of traditional CAR T cell therapy in gastrointestinal cancers faces numerous challenges, including the suppressive tumor microenvironment and limitations in anti-tumor efficacy. The application of engineered bacteria offers a novel strategy to enhance CAR T cell therapy by modulating the tumor microenvironment and boosting immune responses, potentially leading to improved therapeutic outcomes. This review synthesizes the current research advancements related to engineered bacteria-assisted CAR T cell therapy in gastrointestinal cancers, exploring its underlying mechanisms, clinical applications, and future developmental directions.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1581856"},"PeriodicalIF":3.1,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12034723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-04-10eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1564642
Nayoung Kim, Kiven Erique Lukong
{"title":"Treating ER-positive breast cancer: a review of the current FDA-approved SERMs and SERDs and their mechanisms of action.","authors":"Nayoung Kim, Kiven Erique Lukong","doi":"10.3389/or.2025.1564642","DOIUrl":"https://doi.org/10.3389/or.2025.1564642","url":null,"abstract":"<p><p>Breast cancer is one of the most significant causes of mortality among women and the second most prevalent cancer worldwide. Estrogen receptor (ER)-positive breast cancers are the most common molecular subtype of breast cancer, comprising about 70% of breast carcinoma diagnoses worldwide. Endocrine therapy is the foremost strategy for the treatment of ER-positive breast cancer. In the United States, the Food and Drug Administration (FDA) has approved endocrine therapies for ER-positive breast cancers that include selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators/degraders (SERDs) and aromatase inhibitors (AIs). The approved SERMS, tamoxifen, toremifene and raloxifene, are the gold-standard treatments. The only FDA-approved SERD available for treating ER and hormone-positive breast cancers is fulvestrant, and various generations of AIs, including exemestane, letrozole, and anastrozole, have also received FDA approval. Herein, we review the major FDA-approved SERMs and SERDs for treating ER-positive breast cancer, focusing on their mechanisms of action. We also explore molecular events that contribute to the resistance of these drugs to endocrine therapies and combinational strategies with drugs such as cyclin-dependant kinases 4/6 (CDK4/6) inhibitors in clinical trials to combat endocrine drug resistance.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1564642"},"PeriodicalIF":3.1,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12018393/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144003443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-03-14eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1541326
Parminder Singh, Mahalaqua Nazli Khatib, Roopashree R, Mandeep Kaur, Manish Srivastava, Amit Barwal, G V Siva Rajput, Pranchal Rajput, Rukshar Syed, Gajendra Sharma, Sunil Kumar, Muhammed Shabil, Sakshi Pandey, Manvinder Brar, Ganesh Bushi, Rachana Mehta, Sanjit Sah, Khang Wen Goh, Prakasini Satapathy, Abhay M Gaidhane, Shailesh Kumar Samal
{"title":"Advancements and challenges in personalized neoantigen-based cancer vaccines.","authors":"Parminder Singh, Mahalaqua Nazli Khatib, Roopashree R, Mandeep Kaur, Manish Srivastava, Amit Barwal, G V Siva Rajput, Pranchal Rajput, Rukshar Syed, Gajendra Sharma, Sunil Kumar, Muhammed Shabil, Sakshi Pandey, Manvinder Brar, Ganesh Bushi, Rachana Mehta, Sanjit Sah, Khang Wen Goh, Prakasini Satapathy, Abhay M Gaidhane, Shailesh Kumar Samal","doi":"10.3389/or.2025.1541326","DOIUrl":"10.3389/or.2025.1541326","url":null,"abstract":"<p><p>Advancements in personalized neoantigen-based cancer vaccines are ushering in a new era in oncology, targeting unique genetic alterations within tumors to enhance treatment precision and efficacy. Neoantigens, specific to cancer cells and absent in normal tissues, are at the heart of these vaccines, promising to direct the immune system specifically against the tumor, thereby maximizing therapeutic efficacy while minimizing side effects. The identification of neoantigens through genomic and proteomic technologies is central to developing these vaccines, allowing for the precise mapping of a tumor's mutational landscape. Despite advancements, accurately predicting which neoantigens will elicit strong immune responses remains challenging due to tumor variability and the complexity of immune system interactions. This necessitates further refinement of bioinformatics tools and predictive models. Moreover, the efficacy of these vaccines heavily depends on innovative delivery methods that enhance neoantigen presentation to the immune system. Techniques like encapsulating neoantigens in lipid nanoparticles and using viral vectors are critical for improving vaccine stability and delivery. Additionally, these vaccines contribute towards achieving Sustainable Development Goal 3.8, promoting universal health coverage by advancing access to safe and effective cancer treatments. This review delves into the potential of neoantigen-based vaccines to transform cancer treatment, examining both revolutionary advancements and the ongoing challenges they face.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1541326"},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11949952/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-03-05eCollection Date: 2025-01-01DOI: 10.3389/or.2025.1446850
Mariana Rei, João Francisco Bernardes, Antónia Costa
{"title":"Ultrasound in endometrial cancer: evaluating the impact of pre-surgical staging.","authors":"Mariana Rei, João Francisco Bernardes, Antónia Costa","doi":"10.3389/or.2025.1446850","DOIUrl":"10.3389/or.2025.1446850","url":null,"abstract":"<p><p>Preoperative staging in endometrial cancer has recently been implied as an important factor in accurately selecting low-risk cases, ultimately avoiding unnecessary lymph node debulking. Transvaginal ultrasound seems promising in clinical staging as it offers the possibility to assess the depth of myometrial infiltration and cervical stromal invasion. This commonly available, non-invasive, and low-cost modality serves as an accurate alternative to MRI, especially in middle- and low-income countries, where MRI may not be promptly available and cost is an important issue. This review aims to summarize the progressive role of clinical implementation of pelvic ultrasonography in the locoregional staging of endometrial carcinoma and to compare its accuracy with other preoperative methods.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1446850"},"PeriodicalIF":3.1,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11920118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143664055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A new insight into the impact of copy number variations on cell cycle deregulation of luminal-type breast cancer.","authors":"Amir Mahdi Khamaneh, Davoud Jafari-Gharabaghlou, Khalil Ansarin, Pouya Pazooki, Zahra Akbarpour, Behrooz Naghili, Nosratollah Zarghami","doi":"10.3389/or.2025.1516409","DOIUrl":"10.3389/or.2025.1516409","url":null,"abstract":"<p><p>Breast cancer is the most prevalent neoplasm in women. ER<sup>+</sup> (Luminal subtype), representing over 70% of breast tumors, is a genetically diverse group. Structural and Numerical-Chromosomal instability initiates tumor development and is recognized as the primary driver of genetic alteration in luminal breast tumors. Genomic instability refers to the increased tendency of cancer cells to accumulate genomic alterations during cell proliferation. The cell cycle check-point response to constant and stable genomic alterations in tumor cells drives this process. The impact of CNV patterns and aneuploidies in cell cycle and proliferation perturbation has recently been highlighted by scientists in Luminal breast tumors. The impact of chromosomal instability on cancer therapy and prognosis is not a new concept. Still, the degree of emerging genomic instability leads to prognosis alteration following cell cycle deregulation by chromosomal instability could be predicted by CNVs-based reclassification of breast tumors. In this review, we try to explain the effect of CIN in the cell cycle that ended with genomic instability and altered prognosis and the impact of CIN in decision-making for a therapy strategy for patients with luminal breast cancer.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"19 ","pages":"1516409"},"PeriodicalIF":3.1,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11861078/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oncology ReviewsPub Date : 2025-01-20eCollection Date: 2024-01-01DOI: 10.3389/or.2024.1514004
Krzysztof Rutkowski, Michał Gola, Janusz Godlewski, Anna Starzyńska, Giulia Marvaso, Federico Mastroleo, Maria Giulia Vincini, Alice Porazzi, Mattia Zaffaroni, Barbara Alicja Jereczek-Fossa
{"title":"Understanding the role of nerves in head and neck cancers - a review.","authors":"Krzysztof Rutkowski, Michał Gola, Janusz Godlewski, Anna Starzyńska, Giulia Marvaso, Federico Mastroleo, Maria Giulia Vincini, Alice Porazzi, Mattia Zaffaroni, Barbara Alicja Jereczek-Fossa","doi":"10.3389/or.2024.1514004","DOIUrl":"10.3389/or.2024.1514004","url":null,"abstract":"<p><p>Worldwide, head and neck cancers (HNCs) account for approximately 900,000 cases and 500,000 deaths annually, with their incidence continuing to rise. Carcinogenesis is a complex, multidimensional molecular process leading to cancer development, and in recent years, the role of nerves in the pathogenesis of various malignancies has been increasingly recognized. Thanks to the abundant innervation of the head and neck region, peripheral nervous system has gained considerable interest for its possible role in the development and progression of HNCs. Intratumoral parasympathetic, sympathetic, and sensory nerve fibers are emerging as key players and potential targets for novel anti-cancer and pain-relieving medications in different tumors, including HNCs. This review explores nerve-cancer interactions, including perineural invasion (PNI), cancer-related axonogenesis, neurogenesis, and nerve reprogramming, with an emphasis on their molecular mechanisms, mediators and clinical implications. PNI, an adverse histopathologic feature, has been widely investigated in HNCs. However, its prognostic value remains debated due to inconsistent results when classified dichotomously (present/absent). Emerging evidence suggests that quantitative and qualitative descriptions of PNI may better reflect its clinical usefulness. The review also examines therapies targeting nerve-cancer crosstalk and highlights the influence of HPV status on tumor innervation. By synthesizing current knowledge, challenges, and future perspectives, this review offers insights into the molecular basis of nerve involvement in HNCs and the potential for novel therapeutic approaches.</p>","PeriodicalId":19487,"journal":{"name":"Oncology Reviews","volume":"18 ","pages":"1514004"},"PeriodicalIF":3.1,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11791411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143190066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}