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Feature Papers in the Section “Cancer Therapy” in 2025-2026

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

Deadline for manuscript submissions: 31 December 2026 | Viewed by 13556

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Dr. Abdullah Esmail

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Guest Editor

1. Section of Gastrointestinal Oncology—Houston Methodist Neal Cancer Center and Institute of Academic Medicine, 6445 Fannin, OPC-24, Houston, TX 77030, USA
2. Houston Methodist Research Institute, Houston, TX 77030, USA
3. Department of Medicine, Weill Cornell Medical College, New York, NY 10065, USA
Interests: gastrointestinal oncology; gastroenterology; transplant; oncology; targeted therapy; immunotherapy
Special Issues, Collections and Topics in MDPI journals

Dr. Qiang Wang

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Guest Editor

1. Cancer Biology in Medicine, Charles W. Duncan Jr. Department of Medicine, Academic Institute, Houston Methodist, Houston, TX, USA
2. Dr. Mary and Ron Neal Cancer Center & Houston Methodist Research Institute, Houston, TX, USA
Interests: cancer biology; tumor microenvironment cross-talk; immuno-oncology; T-cell redirection therapies; mechanisms of drug resistance
Special Issues, Collections and Topics in MDPI journals

Prof. Dr. Hiroyuki Takei

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Guest Editor

Department of Breast Surgery, Sanno Hospital, 8-10-16 Akasaka, Minato-ku, Tokyo 107-0052, Japan
Interests: breast cancer; endocrine therapy; chemotherapy; surgical therapy; tumor angiogenesis
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the Special Issue “Feature Paper in Section “Cancer Therapy” in 2024” (https://www.mdpi.com/journal/cancers/special_issues/851NXE23AN).

As a result of the development and improvement of modalities for systematic and localized treatment, the field of oncology has undergone a complete revolution. To effectively manage the progression of cancer, it is essential to have therapeutic approaches that are both precise and targeted, as well as those that are particular to the affected area and may be utilized at an early stage. The major method that is utilized for people who are qualified to undergo surgical removal of their tumor is one of these. Chemotherapy is a medication that is frequently used in the treatment of cancer, yet it is notorious for the significant toxicity that it causes in patients. On the other hand, as a pharmaceutical intervention, it is currently being utilized in conjunction with immunotherapy increasingly frequently. The effectiveness of immunotherapy is based on its capacity to strengthen the immune system of the host, which makes it an appropriate supplement to the standard of care that has been established for long-term treatment. In addition, immunotherapy has undergone substantial changes, particularly since the Food and Drug Administration (FDA) authorized it for the treatment of more advanced cancers. Additionally, the increasing validity and effectiveness of immunotherapies have been demonstrated in recent clinical research trials, which have been conducted all over the world with the purpose of improving oncology treatments. To improve both survival rates and quality of life in the field of cancer, it is essential to continue developing each of these therapy techniques. This Special Issue will discuss the innovations recently made in chemo- and immunotherapy and other developments and specializations in the field, such as targeted therapy.

Dr. Abdullah Esmail
Dr. Qiang Wang
Prof. Dr. Hiroyuki Takei
Guest Editors

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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-anonymized 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.

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Keywords

chemotherapy
immunotherapy for cancer
oncology
systemic treatment and targeted therapy.

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Published Papers (10 papers)

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Research

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30 pages, 27631 KB

Open AccessFeature PaperArticle

Fexofenadine Induces ROS-Dependent Mitochondrial Dysfunction and Suppresses PI3K/AKT and MAPK Signaling in Cervical and Lung Cancer Cells

by Ewa Trybus and Wojciech Trybus

Cancers 2026, 18(13), 2156; https://doi.org/10.3390/cancers18132156 - 4 Jul 2026

Viewed by 507

Abstract

Background/Objectives: Drug repurposing has emerged as a promising strategy for identifying novel anticancer agents among clinically established drugs. Fexofenadine, a second-generation H1 antihistamine, has been proposed as a candidate for repurposing in oncology; however, the molecular mechanisms underlying its biological activity remain insufficiently characterized. This study investigated the effects of fexofenadine on oxidative stress, mitochondrial function, apoptosis, and pro-survival signaling pathways in cervical and lung cancer cells. Methods: HeLa and A549 cancer cells, as well as non-tumorigenic Beas-2B epithelial cells, were exposed to fexofenadine under in vitro conditions. Cell viability, apoptosis, reactive oxygen species generation, mitochondrial membrane potential, DNA damage, autophagy-associated responses, and PI3K/AKT and MAPK/ERK pathway activation were assessed using flow cytometry, fluorescence microscopy, electron microscopy, and biochemical assays. Three-dimensional spheroid cultures and N-acetyl-L-cysteine rescue experiments were additionally employed to evaluate biological relevance and the contribution of oxidative stress. Results: Fexofenadine induced concentration-dependent accumulation of reactive oxygen species, mitochondrial membrane depolarization, Bcl-2 inactivation, caspase-3/7 activation, DNA damage, and apoptotic cell death in HeLa and A549 cells. Antioxidant pretreatment with N-acetyl-L-cysteine significantly reduced oxidative stress, attenuated mitochondrial dysfunction, and partially suppressed apoptosis. Fexofenadine was associated with reduced PI3K/AKT and MAPK/ERK pathway activation and promoted autophagy-associated responses. In three-dimensional spheroid cultures, treatment disrupted spheroid integrity and increased apoptotic cell death. Non-tumorigenic Beas-2B cells exhibited lower sensitivity to treatment than malignant cells. Conclusions: Fexofenadine disrupts redox homeostasis and is associated with reduced activation of pro-survival signaling pathways, resulting in oxidative stress-associated mitochondrial dysfunction and apoptosis in cancer cells. These findings provide mechanistic support for further evaluation of fexofenadine as a candidate for anticancer drug repurposing, while additional pharmacokinetic and in vivo studies are required to determine its translational relevance. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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15 pages, 886 KB

Open AccessArticle

Evaluation of Clinical Outcomes in Dogs with Malignant Intranasal Tumors Treated with Radiotherapy: A Retrospective Study of 40 Cases

by Simone Carvalho dos Santos Cunha, Bianca Moreira Angelim, Rebeca Herdade, Karen Cristina de Souza da Rocha Dias, Laís Calazans Menescal Linhares, Rafael Costa Bitencourt, Guilherme Andraus Bispo, Felipe Noleto de Paiva and Andrigo Barboza de Nardi

Cancers 2026, 18(12), 2013; https://doi.org/10.3390/cancers18122013 - 22 Jun 2026

Viewed by 1183

Abstract

Background/Objectives: Intranasal tumors are common malignancies in dogs, characterized by locally aggressive behavior and clinical signs such as epistaxis, nasal discharge, and facial deformity. Radiotherapy (RT) is considered the treatment of choice due to anatomical limitations to surgical resection. This study aimed to evaluate clinical outcomes, toxicity, and prognostic factors in dogs with primary malignant intranasal tumors treated with cobalt-60–based megavoltage radiotherapy. Methods: This retrospective study included 40 dogs with histopathologically confirmed primary malignant intranasal tumors treated between September 2018 and February 2025 at a veterinary radiotherapy clinic in Rio de Janeiro, Brazil. Medical records were reviewed for patient demographics, tumor characteristics, treatment protocols, response, toxicity, and survival outcomes. Tumors were staged using modified Adams criteria based on computed tomography. Definitive-intent protocols (n = 32) delivered 48–54 Gy in 10–13 fractions administered three to five times weekly, while palliative protocols consisted of either four fractions of 8 Gy delivered once weekly or five fractions of 4 Gy delivered daily. Results: Adenocarcinoma was the most common histologic subtype (42.5%), and 82.5% of dogs had stage III–IV disease. The objective response rate was 82.5% (CR: 17.5%; PR: 65.0%), with clinical benefit observed in 92.5% of cases. Acute toxicity was frequent but manageable, primarily affecting skin, oral mucosa, and eyes. Overall median progression-free interval (PFI) and survival time (MST) were 382 days and 430 days, respectively. Stage IV disease was significantly associated with shorter survival when compared to stage I-III (MST 345 vs. 1063 days, respectively; p = 0.016). Treatment response was significantly associated with PFI in univariate analysis (p < 0.05). Conclusions: Radiotherapy provided high response rates and meaningful clinical benefit with acceptable toxicity in dogs with malignant intranasal tumors, highlighting the importance of early diagnosis and treatment. Further prospective studies with standardized protocols are warranted. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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17 pages, 1739 KB

Open AccessArticle

Total Neoadjuvant Approach for Borderline Resectable and Locally Advanced Pancreatic Adenocarcinoma—UK Tertiary Cancer Centre Experience

by Kai Tai Derek Yeung, Simon Gomberg, William Hodgson, Petula Jefferies, David Cunningham, Sheela Rao, Ian Chau, Naureen Starling, Charlotte Fribbens, Avani Athauda, Diana Tait, Irene Chong, Arabella Hunt, Magnus T. Dillon, Sacheen Kumar, Long R. Jiao, Ricky H. Bhogal and Katharine Aitken

Cancers 2026, 18(10), 1597; https://doi.org/10.3390/cancers18101597 - 14 May 2026

Viewed by 795

Abstract

Introduction: Pancreatic ductal adenocarcinoma (PDAC) remains a leading cause of cancer-related mortality. Radiological distinctions between borderline resectable (BR) and locally advanced disease (LA) are increasingly recognised as imperfect when considered without dynamic assessment. Neoadjuvant therapy (NAT) improves outcomes through tumour downstaging and early treatment of occult metastatic disease, but the optimal NAT strategy, particularly in BR disease, remains uncertain. Published data evaluating combined systemic anti-cancer therapies (SACT) with or without chemoradiation (CRT) are limited and heterogeneous. Methods: This is a single-centre retrospective analysis of 44 patients with BR PDAC and a comparator cohort of 121 patients with LA PDAC treated with a total neoadjuvant approach of SACT with or without CRT and surgical resection between June 2017 and September 2022. Results: Median overall survival (OS) did not differ significantly between BR and LA disease (18 vs. 16 months, p = 0.14). Following NAT, 47.7% of BR and 18.1% of LA patients were anatomically suitable for surgical resection. Among unresected BR and LA patients, those treated with CRT in addition to SACT had a median OS of 18 and 21 months respectively. In the resected subgroup, resection margin status was the primary factor associated with survival; with R0 resection conferring a substantial OS advantage over R1, irrespective of initial BR/LA classification as diagnosis (47 vs. 22 months, p < 0.001). Conclusions: Despite anatomical differences at diagnosis, BR and LA PDAC demonstrated comparable survival outcomes when treated with total neoadjuvant strategies in this cohort. These findings challenge traditional radiological staging-based treatment paradigms and confirm that a margin-negative surgical resection offered the greatest opportunity for long-term survival for BR/LA PDAC patients. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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21 pages, 740 KB

Open AccessArticle

Body Mass Index and Outcomes in HR+/HER2− Metastatic Breast Cancer Treated with Palbociclib: Insights from a National Real-World Study

by Larisa Maria Badau, Paul Epure, Madalin-Marius Margan, Roxana Margan, Andrei Dorin Ciocoiu, Cristina Marinela Oprean and Brigitha Vlaicu

Cancers 2026, 18(9), 1379; https://doi.org/10.3390/cancers18091379 - 26 Apr 2026

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Abstract

Background/Objectives: The prognostic and predictive role of BMI in patients with HR+/HER2− MBC remains controversial, particularly in the era of CDK4/6 inhibitors. This study aimed to evaluate the association between baseline BMI and clinical outcomes in patients treated with palbociclib in a real-world setting. Methods: We conducted a multicenter retrospective observational cohort study including 326 patients with HR+/HER2− MBC treated with palbociclib in combination with endocrine therapy across six oncology centers in Romania. Only patients who received palbociclib for at least three months were included. Patients were stratified according to BMI into <25 kg/m² and ≥25 kg/m² groups. PFS and OS were the primary endpoints, while ORR and CBR were secondary endpoints. Results: Among the 326 patients, 66.56% were classified as overweight or obese (BMI ≥ 25 kg/m²). Median PFS was 23.66 months in the BMI < 25 group and 26.78 months in the BMI ≥ 25 group, with no statistically significant difference (HR 0.86; 95% CI 0.62–1.20; p = 0.373). Median OS was not reached in the BMI < 25 group and was 43.73 months in the BMI ≥ 25 group, also without a significant difference (HR 0.82; 95% CI 0.52–1.30; p = 0.397). ORR (29.07% vs. 28.89%) and CBR (90.70% vs. 88.33%) were comparable between BMI groups. In multivariate analysis, liver metastases and brain metastases were independently associated with worse outcomes, whereas BMI was not an independent prognostic factor. Conclusions: In this selected real-world cohort of patients with HR+/HER2− MBC who tolerated at least three months of palbociclib, baseline BMI was not associated with treatment response, PFS, or OS. While clinically informative, these results should not be interpreted as definitive evidence that body weight has no influence on palbociclib efficacy, given the methodological constraints of the analysis. BMI alone may be insufficient to capture the complex interplay between body composition and treatment outcomes, highlighting the need for more refined biomarkers of body composition in this setting. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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16 pages, 1450 KB

Open AccessArticle

Therapeutic Potential of miR-4711-5p in Pancreatic Cancer: Antitumor Activity and Mechanistic Insights

by Yuhki Yokoyama, Yoshihiro Morimoto, Hiroyuki Yamamoto, Shihori Kouda, Shiho Kawanami, Ruijia Yang, Yingjue Zhang, Manami Tsujimoto, Nanami Nagata, Yuki Shimomura, Kana Nishida, Tsuyoshi Hata, Akira Inoue, Satoshi Shibata, Hirofumi Yamamoto and Masaki Mori

Cancers 2026, 18(7), 1104; https://doi.org/10.3390/cancers18071104 - 29 Mar 2026

Viewed by 856

Abstract

Background/Aim: Pancreatic cancer remains one of the most lethal malignancies, with limited therapeutic options and an extremely poor prognosis. MicroRNAs (miRNAs), which regulate gene expression at the post-transcriptional level, have emerged as promising candidates for next-generation cancer therapeutics. The purpose of this study is to clarify the feasibility of miR-4711 as a potential therapeutic option against pancreatic cancer. Materials and Methods: The effects of miR-4711-5p were examined in pancreatic cancer cell lines with respect to cell proliferation, apoptosis, cancer stemness, cell cycle progression, and invasive capacity. RNA sequencing and in silico analyses were performed to identify potential target genes of miR-4711-5p. For in vivo safety evaluation, miR-4711-5p was formulated with super carbonate apatite, a delivery vehicle that is already amenable to large-scale production, and administered to cynomolgus monkeys. A nucleic acid dose equivalent to 10 times the effective dose observed in prior mouse efficacy studies was used. General clinical conditions, body weight, food consumption, ophthalmologic findings, electrocardiography, blood pressure, hematological and biochemical parameters, and histopathological changes were systematically assessed. Results: miR-4711-5p significantly suppressed cancer stemness, cell proliferation, and invasion, while inducing apoptosis and delaying cell cycle progression in pancreatic cancer cells. RNA sequencing and bioinformatic analyses identified MET, CTSA, and ANO1 as potential target genes of miR-4711-5p. In the cynomolgus monkey study, administration of miR-4711-5p formulated with super carbonate apatite resulted in no apparent differences compared with the control group in body weight, clinical observations, laboratory parameters, or histopathological findings, indicating the absence of treatment-related adverse effects even at a supra-therapeutic dose. Conclusions: These findings demonstrate that miR-4711-5p exerts potent antitumor effects against pancreatic cancer cells while exhibiting a favorable safety profile in a non-human primate model. Collectively, this study provides strong preclinical evidence supporting miR-4711-5p as a novel and safe therapeutic strategy for pancreatic cancer and represents an important step toward clinical application. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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20 pages, 5495 KB

Open AccessArticle

Canady Helios Cold Plasma Induces Non-Thermal (24 °C), Non-Contact Irreversible Electroporation and Selective Tumor Cell Death at Surgical Margins

by Saravana R. K. Murthy, Taisen Zhuang, Olivia Z. Jones, Yasmine Dakak, Michael Keidar, Aviram Nissan and Jerome Canady

Cancers 2025, 17(23), 3869; https://doi.org/10.3390/cancers17233869 - 2 Dec 2025

Cited by 1 | Viewed by 1557

Abstract

Background: The Canady Helios Cold Plasma (CHCP) system is a non-thermal, non-contact cold atmospheric plasma technology that generates transient electric fields and reactive species capable of disrupting cancer cell membranes. This study investigated the voltage-dependent membrane irreversible electroporation (IRE) dynamics induced by CHCP across biologically distinct breast cancer subtypes. Methods: Four breast cancer cell lines, triple-negative (MDA-MB-231 and Hs578T), ER⁺/PR⁺/HER2⁻ (MCF-7), and ER⁺/PR⁺/HER2⁺ (BT-474), were exposed to CHCP for 5 min at 25 V (~1675 V/cm PTEF) or 30 V (~2010 V/cm), either directly or with Plasma Activated Media (PAM). Membrane permeability was assessed by propidium iodide (PI) uptake over 120 min. Morphological changes were evaluated microscopically. Functional electroporation was examined via BCL2A1-targeting siRNA delivery and clonogenic survival. Ex vivo analyses of Phase I clinical trial tumor specimens (NCT04267575) were performed to characterize CHCP-induced tissue responses. Results: CHCP produced voltage- and time-dependent membrane permeabilization in all breast cancer cell lines, with 30 V generating robust and sustained PI uptake compared to transient effects at 25 V. Treated cells exhibited morphological features consistent with membrane disruption. CHCP enabled intracellular siRNA delivery and significantly reduced clonogenic potential, confirming functional pore formation. Ex vivo CHCP treatment selectively damaged tumor cells while sparing adjacent non-cancerous tissue. Conclusions: This study demonstrates CHCP as a non-thermal (24 °C), non-contact plasma-based IRE platform which induces controlled membrane permeabilization and selective cancer cell death. CHCP offers a translational strategy to eradicate residual tumor cells at the surgical margins, and prevent local recurrence, positioning it as a versatile adjunct in precision surgical oncology. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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18 pages, 1179 KB

Open AccessArticle

Incidence and Clinical Features of Pseudoprogression in Brain Metastases After Immune-Checkpoint Inhibitor Therapy: A Retrospective Study

by Chris W. Govaerts, Miranda C. A. Kramer, Ingeborg Bosma, Frank A. E. Kruyt, Frederike Bensch, J. Marc C. van Dijk, Mathilde Jalving and Anouk van der Hoorn

Cancers 2025, 17(15), 2425; https://doi.org/10.3390/cancers17152425 - 22 Jul 2025

Cited by 3 | Viewed by 3289 | Correction

Abstract

Background: Pseudoprogression is known to occur after immune-checkpoint inhibitor (ICI) therapy in brain metastasis and can complicate clinical decision-making. Still, its incidence, timing, and clinical presentation remain unclear. A retrospective cohort study in melanoma and non-small cell lung cancer brain metastasis patients was conducted to address this. Materials and Methods: Brain metastasis patients showing progression on MRI according to response assessment in neuro-oncology brain metastases criteria after starting ICI therapy were included, irrespective of prior irradiation. Lesions were classified as tumour progression (TP) or pseudoprogression based on three-month radiological follow-up or histopathology. TP was assigned if progression was again shown at three months. Pseudoprogression was assigned if lesions showed stability, partial, or complete response at three months. ‘Non-classified’ lesions were those with new or changed treatment during follow-up. Results: A cohort of 98 patients with 233 lesions was included over a 13-year period; 170 lesions were considered non-classified, and 41 and 22 lesions were classified as TP and pseudoprogression respectively. This resulted in a lesion- and patient-specific incidence for pseudoprogression of 9.4% and 17.3% respectively. Due to the large number of lesions that could not be classified, as is the case in clinical practice, the reported incidence in this study is likely an underestimation and can be seen as a ‘minimum’ incidence rate. Ten pseudoprogression (45.5%) and 13 (31.7%) TP lesions were previously irradiated. Pseudoprogression occurred at a median of 2.7 months after starting ICI therapy. The only clinical feature distinguishing patients with TP from pseudoprogression was that TP patients were more likely to need dexamethasone for neurological symptoms. Conclusions: Pseudoprogression has a lesion-specific incidence rate of at least 9.4% and occurs at a median of 2.7 months after starting ICI therapy. Severe neurological symptoms requiring dexamethasone may be a clinical feature typical for TP. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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Review

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31 pages, 1192 KB

Open AccessReview

Next-Generation Immune Checkpoint Inhibitors in Gastrointestinal Cancers: Mechanisms, Resistance, and Emerging Therapeutic Strategies

by Mariam Ismail, Zaid Alabed, Khaled Alhallaq, Ebtesam Al-Najjar, Nour Mustafa, Yacoub Aldroubi, Yazan Hamdaneh and Abdullah Esmail

Cancers 2026, 18(16), 2593; https://doi.org/10.3390/cancers18162593 - 12 Aug 2026

Viewed by 265

Abstract

Immune checkpoint inhibitors (ICIs) have significantly changed the treatment landscape of several gastrointestinal (GI) malignancies, particularly microsatellite instability-high (MSI-H) and mismatch repair-deficient (dMMR) tumors. However, most GI cancers remain resistant to current PD-1/PD-L1-based immunotherapy because of complex and highly suppressive tumor microenvironments characterized by immune stromal exclusion, myeloid-driven immune suppression, defective antigen presentation, and adaptive immune resistance mechanisms. Emerging evidence suggests that alternative inhibitory pathways, including lymphocyte activation gene-3 (LAG-3), T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT), T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), and V-domain Ig suppressor of T-cell activation (VISTA), contribute substantially to persistent T-cell dysfunction and resistance to checkpoint blockade. This review summarizes the immune landscape of GI malignancies and discusses the biological mechanisms underlying resistance to current ICIs. We highlight the evolving role of next-generation immune checkpoints, ongoing clinical development of novel inhibitors, and emerging combination strategies involving chemotherapy, anti-angiogenic therapy, radiation, bispecific antibodies, and tumor microenvironment modulation. In addition, we discuss current limitations in biomarker development and the growing role of circulating tumor DNA, spatial immune profiling, and multi-omics approaches in patient selection. Finally, we explore future directions aimed at improving precision immunotherapy and expanding durable responses across GI cancers. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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Other

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4 pages, 313 KB

Open AccessCorrection

Correction: Govaerts et al. Incidence and Clinical Features of Pseudoprogression in Brain Metastases After Immune-Checkpoint Inhibitor Therapy: A Retrospective Study. Cancers 2025, 17, 2425

by Chris W. Govaerts, Miranda C. A. Kramer, Ingeborg Bosma, Frank A. E. Kruyt, Frederike Bensch, J. Marc C. van Dijk, Mathilde Jalving and Anouk van der Hoorn

Cancers 2026, 18(4), 572; https://doi.org/10.3390/cancers18040572 - 10 Feb 2026

Viewed by 601

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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8 pages, 705 KB

Open AccessViewpoint

Rethinking EPO: A Paradigm Shift in Oncology?

by Jean-Marc Ferrero, Baharia Mograbi, Rym Bouriga, Jocelyn Gal and Gérard Milano

Cancers 2025, 17(23), 3875; https://doi.org/10.3390/cancers17233875 - 3 Dec 2025

Cited by 2 | Viewed by 2270

Abstract

Erythropoietin (EPO) is a hormone mainly produced by the kidney. EPO stimulates red blood cell production in response to hypoxia. EPO represents one of the most compelling paradoxes in medical oncology. For decades, recombinant EPO has been prescribed as an effective therapy for cancer-related anemia and fatigue, significantly improving patients’ quality of life while reducing their dependence on blood transfusions. Yet, accumulating scientific evidence knowledge has highlighted the complex interactions between EPO and tumor biology that extend well beyond its hematopoietic functions. The putative expression of EPO receptors on tumor cells has raised concerns about a potential role of EPO in promoting tumor progression, although conclusive clinical evidence remains lacking. Recent studies have revealed that EPO may contribute to immunosuppressive mechanisms within the tumor microenvironment, thereby reshaping our understanding of its risk/benefit profile in oncology. This evolving body of evidence calls for an objective reassessment of EPO’s dual nature as both a therapeutic ally and a potential oncological threat, in order to bring more caution around decision-making in the current era of strongly evolving cancer care. Full article

(This article belongs to the Special Issue Feature Papers in the Section “Cancer Therapy” in 2025-2026)

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