Journal Description
Cancers
Cancers
is a peer-reviewed, open access journal of oncology, published semimonthly online by MDPI. The Irish Association for Cancer Research (IACR), Spanish Association for Cancer Research (ASEICA), Biomedical Research Centre (CIBM), British Neuro-Oncology Society (BNOS) and Spanish Group for Cancer Immuno-Biotherapy (GÉTICA) are affiliated with Cancers and their members receive a discount on the article processing charges.
- Open Access— free for readers, with article processing charges (APC) paid by authors or their institutions.
- High Visibility: indexed within Scopus, SCIE (Web of Science), PubMed, PMC, Embase, CAPlus / SciFinder, and other databases.
- Journal Rank: JCR - Q2 (Oncology) / CiteScore - Q1 (Oncology)
- Rapid Publication: manuscripts are peer-reviewed and a first decision is provided to authors approximately 17.9 days after submission; acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the second half of 2023).
- Recognition of Reviewers: reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.
- Sections: published in 18 topical sections.
- Companion journals for Cancers include: Radiation and Onco.
Impact Factor:
5.2 (2022);
5-Year Impact Factor:
5.6 (2022)
Latest Articles
Interventional Treatments of Colorectal Liver Metastases Using Thermal Ablation and Transarterial Chemoembolization: A Single-Center Experience over 26 Years
Cancers 2024, 16(9), 1756; https://doi.org/10.3390/cancers16091756 (registering DOI) - 30 Apr 2024
Abstract
The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department
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The aim of this study was to analyze the long-term results of different locoregional treatments for colorectal cancer liver metastases (CRLM), including transarterial chemoembolization (TACE), laser-induced thermotherapy (LITT) and microwave ablation (MWA). A total of 2140 patients with CRLM treated at our department between 1993 and 2020 were included in this retrospective study. The patients were divided into the following groups: LITT (573 patients; median age: 62 years), TACE + LITT (346 patients; median age: 62 years), MWA (67 patients; median age: 59 years), TACE + MWA (152 patients; median age: 65 years), and TACE (1002 patients; median age: 62 years). Median survival was 1.9 years in the LITT group and 1.7 years in the TACE + LITT group. The median survival times in the MWA group and TACE + MWA group were 3.1 years and 2.1 years, respectively. The median survival in the TACE group was 0.8 years. The 1-, 3-, and 5-year survival rates were 77%, 27%, and 9% in the LITT group and 74%, 18%, and 5% in the TACE + LITT group, respectively. The corresponding survival rates were 80%, 55%, and 33% in the MWA group, 74%, 36%, and 20% in the TACE + MWA group and 37%, 3%, and 0% in the TACE group, respectively. The long-term results of this study demonstrate the efficacy of locoregional treatments in treating patients with CRLM. The longest survival was found in the MWA group, followed by the combination therapy of TACE and MWA.
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(This article belongs to the Section Cancer Epidemiology and Prevention)
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Activation of the Anaphase Promoting Complex Restores Impaired Mitotic Progression and Chemosensitivity in Multiple Drug-Resistant Human Breast Cancer
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Mathew Lubachowski, Cordell VanGenderen, Sarah Valentine, Zach Belak, Gerald Floyd Davies, Terra Gayle Arnason and Troy Anthony Alan Harkness
Cancers 2024, 16(9), 1755; https://doi.org/10.3390/cancers16091755 - 30 Apr 2024
Abstract
The development of multiple-drug-resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrate that the Anaphase Promoting Complex (APC) is impaired in
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The development of multiple-drug-resistant (MDR) cancer all too often signals the need for alternative toxic therapy or palliative care. Our recent in vivo and in vitro studies using canine MDR lymphoma cancer cells demonstrate that the Anaphase Promoting Complex (APC) is impaired in MDR cells compared to normal canine control and drug-sensitive cancer cells. Here, we sought to establish whether this phenomena is a generalizable mechanism independent of species, malignancy type, or chemotherapy regime. To test the association of blunted APC activity with MDR cancer behavior, we used matched parental and MDR MCF7 human breast cancer cells, and a patient-derived xenograft (PDX) model of human triple-negative breast cancer. We show that APC activating mechanisms, such as APC subunit 1 (APC1) phosphorylation and CDC27/CDC20 protein associations, are reduced in MCF7 MDR cells when compared to chemo-sensitive matched cell lines. Consistent with impaired APC function in MDR cells, APC substrate proteins failed to be effectively degraded. Similar to our previous observations in canine MDR lymphoma cells, chemical activation of the APC using Mad2 Inhibitor-1 (M2I-1) in MCF7 MDR cells enhanced APC substrate degradation and resensitized MDR cells in vitro to the cytotoxic effects of the alkylating chemotherapeutic agent, doxorubicin (DOX). Using cell cycle arrest/release experiments, we show that mitosis is delayed in MDR cells with elevated substrate levels. When pretreated with M2I-1, MDR cells progress through mitosis at a faster rate that coincides with reduced levels of APC substrates. In our PDX model, mice growing a clinically MDR human triple-negative breast cancer tumor show significantly reduced tumor growth when treated with M2I-1, with evidence of increased DNA damage and apoptosis. Thus, our results strongly support the hypothesis that APC impairment is a driver of aggressive tumor development and that targeting the APC for activation has the potential for meaningful clinical benefits in treating recurrent cases of MDR malignancy.
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(This article belongs to the Special Issue Molecular Insights into Drug Resistance in Cancer)
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Antiretroviral Drug Repositioning for Glioblastoma
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Sarah R. Rivas, Mynor J. Mendez Valdez, Jay S. Chandar, Jelisah F. Desgraves, Victor M. Lu, Leo Ampie, Eric B. Singh, Deepa Seetharam, Christian K. Ramsoomair, Anna Hudson, Shreya M. Ingle, Vaidya Govindarajan, Tara T. Doucet-O’Hare, Catherine DeMarino, John D. Heiss, Avindra Nath and Ashish H. Shah
Cancers 2024, 16(9), 1754; https://doi.org/10.3390/cancers16091754 - 30 Apr 2024
Abstract
Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in
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Outcomes for glioblastoma (GBM) remain poor despite standard-of-care treatments including surgical resection, radiation, and chemotherapy. Intratumoral heterogeneity contributes to treatment resistance and poor prognosis, thus demanding novel therapeutic approaches. Drug repositioning studies on antiretroviral therapy (ART) have shown promising potent antineoplastic effects in multiple cancers; however, its efficacy in GBM remains unclear. To better understand the pleiotropic anticancer effects of ART on GBM, we conducted a comprehensive drug repurposing analysis of ART in GBM to highlight its utility in translational neuro-oncology. To uncover the anticancer role of ART in GBM, we conducted a comprehensive bioinformatic and in vitro screen of antiretrovirals against glioblastoma. Using the DepMap repository and reversal of gene expression score, we conducted an unbiased screen of 16 antiretrovirals in 40 glioma cell lines to identify promising candidates for GBM drug repositioning. We utilized patient-derived neurospheres and glioma cell lines to assess neurosphere viability, proliferation, and stemness. Our in silico screen revealed that several ART drugs including reverse transcriptase inhibitors (RTIs) and protease inhibitors (PIs) demonstrated marked anti-glioma activity with the capability of reversing the GBM disease signature. RTIs effectively decreased cell viability, GBM stem cell markers, and proliferation. Our study provides mechanistic and functional insight into the utility of ART repurposing for malignant gliomas, which supports the current literature. Given their safety profile, preclinical efficacy, and neuropenetrance, ARTs may be a promising adjuvant treatment for GBM.
Full article
(This article belongs to the Special Issue Glioblastoma: Advances in Molecular Insights and Therapeutic Strategies)
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The Evolving Classification of Meningiomas: Integration of Molecular Discoveries to Inform Patient Care
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S. Joy Trybula, Mark W. Youngblood, Constantine L. Karras, Nikhil K. Murthy, Amy B. Heimberger, Rimas V. Lukas, Sean Sachdev, John A. Kalapurakal, James P. Chandler, Daniel J. Brat, Craig M. Horbinski and Stephen T. Magill
Cancers 2024, 16(9), 1753; https://doi.org/10.3390/cancers16091753 - 30 Apr 2024
Abstract
Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart’s description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication
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Meningioma classification and treatment have evolved over the past eight decades. Since Bailey, Cushing, and Eisenhart’s description of meningiomas in the 1920s and 1930s, there have been continual advances in clinical stratification by histopathology, radiography and, most recently, molecular profiling, to improve prognostication and predict response to therapy. Precise and accurate classification is essential to optimizing management for patients with meningioma, which involves surveillance imaging, surgery, primary or adjuvant radiotherapy, and consideration for clinical trials. Currently, the World Health Organization (WHO) grade, extent of resection (EOR), and patient characteristics are used to guide management. While these have demonstrated reliability, a substantial number of seemingly benign lesions recur, suggesting opportunities for improvement of risk stratification. Furthermore, the role of adjuvant radiotherapy for grade 1 and 2 meningioma remains controversial. Over the last decade, numerous studies investigating the molecular drivers of clinical aggressiveness have been reported, with the identification of molecular markers that carry clinical implications as well as biomarkers of radiotherapy response. Here, we review the historical context of current practices, highlight recent molecular discoveries, and discuss the challenges of translating these findings into clinical practice.
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(This article belongs to the Special Issue Molecular Pathology of Brain Tumors)
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Drivers Underlying Metastasis and Relapse in Medulloblastoma and Targeting Strategies
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Karl O. Holmberg, Anna Borgenvik, Miao Zhao, Géraldine Giraud and Fredrik J. Swartling
Cancers 2024, 16(9), 1752; https://doi.org/10.3390/cancers16091752 - 30 Apr 2024
Abstract
Medulloblastomas comprise a molecularly diverse set of malignant pediatric brain tumors in which patients are stratified according to different prognostic risk groups that span from very good to very poor. Metastasis at diagnosis is most often a marker of poor prognosis and the
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Medulloblastomas comprise a molecularly diverse set of malignant pediatric brain tumors in which patients are stratified according to different prognostic risk groups that span from very good to very poor. Metastasis at diagnosis is most often a marker of poor prognosis and the relapse incidence is higher in these children. Medulloblastoma relapse is almost always fatal and recurring cells have, apart from resistance to standard of care, acquired genetic and epigenetic changes that correlate with an increased dormancy state, cell state reprogramming and immune escape. Here, we review means to carefully study metastasis and relapse in preclinical models, in light of recently described molecular subgroups. We will exemplify how therapy resistance develops at the cellular level, in a specific niche or from therapy-induced secondary mutations. We further describe underlying molecular mechanisms on how tumors acquire the ability to promote leptomeningeal dissemination and discuss how they can establish therapy-resistant cell clones. Finally, we describe some of the ongoing clinical trials of high-risk medulloblastoma and suggest or discuss more individualized treatments that could be of benefit to specific subgroups.
Full article
(This article belongs to the Special Issue The Biological Diversity and Therapeutic Implications of Medulloblastoma Metastases and Recurrence)
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Challenges and Opportunities in Breast Cancer Care in Low-Resourced Countries, Jordan as An Example
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Hikmat Abdel-Razeq and Asem Mansour
Cancers 2024, 16(9), 1751; https://doi.org/10.3390/cancers16091751 - 30 Apr 2024
Abstract
Jordan is a relatively small country with a rapidly growing population and a challenged economy. Breast cancer is the most diagnosed cancer among women worldwide and also in Jordan. Though the age-standardized rate (ASR) of breast cancer incidence is still lower than that
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Jordan is a relatively small country with a rapidly growing population and a challenged economy. Breast cancer is the most diagnosed cancer among women worldwide and also in Jordan. Though the age-standardized rate (ASR) of breast cancer incidence is still lower than that in Western societies, the number of newly diagnosed cases continues to increase, involving younger women, and new cases are usually detected at more advanced stages. Improvements in breast cancer care across the health care continuum, including early detection, prevention, treatment, and survivorship and palliative care, have become very visible, but may not match the magnitude of the problem. More organized, goal-oriented work is urgently needed to downstage the disease and improve awareness of, access to, and participation in early detection programs. The cost of recently introduced anti-cancer therapies poses a great challenge, but the impact of these therapies on treatment outcomes, including overall survival, is becoming very noticeable. Though the concept of a multidisciplinary approach to breast cancer treatment is often used at most health care facilities, its implementation in real practice varies significantly. The availability of breast reconstruction procedures, survivorship programs, germline genetic testing, counselling, and palliative care is improving, but these are not widely practiced. In this manuscript, we review the status of breast cancer in Jordan and highlight some of the existing challenges and opportunities.
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(This article belongs to the Special Issue Health Services Research in Cancer Care)
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Anticancer Activity of Encapsulated Pearl Millet Polyphenol-Rich Extract against Proliferating and Non-Proliferating Breast Cancer Cells In Vitro
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Latifa Hajri, Anna Lewińska, Iwona Rzeszutek, Bernadetta Oklejewicz, Renata Wojnarowska-Nowak, Agnieszka Krogul-Sobczak, Ewa Szpyrka, Alfredo Aires, Soumaya Ghodbane, Mohamed Ammari and Maciej Wnuk
Cancers 2024, 16(9), 1750; https://doi.org/10.3390/cancers16091750 - 30 Apr 2024
Abstract
Plant-derived polyphenols are bioactive compounds with potential health-promoting properties including antioxidant, anti-inflammatory, and anticancer activity. However, their beneficial effects and biomedical applications may be limited due to their low bioavailability. In the present study, we have considered a microencapsulation-based drug delivery system to
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Plant-derived polyphenols are bioactive compounds with potential health-promoting properties including antioxidant, anti-inflammatory, and anticancer activity. However, their beneficial effects and biomedical applications may be limited due to their low bioavailability. In the present study, we have considered a microencapsulation-based drug delivery system to investigate the anticancer effects of polyphenol-rich (apigenin, caffeic acid, and luteolin) fractions, extracted from a cereal crop pearl millet (Pennisetum glaucum), using three phenotypically different cellular models of breast cancer in vitro, namely triple negative HCC1806, ER-positive HCC1428, and HER2-positive AU565 cells. Encapsulated polyphenolic extract induced apoptotic cell death in breast cancer cells with different receptor status, whereas it was ineffective against non-tumorigenic MCF10F cells. Encapsulated polyphenolic extract was also found to be cytotoxic against drug-resistant doxorubicin-induced senescent breast cancer cells that were accompanied by increased levels of apoptotic and necrotic markers, cell cycle inhibitor p21 and proinflammatory cytokine IL8. Furthermore, diverse responses to the stimulation with encapsulated polyphenolic extract in senescent breast cancer cells were observed, as in the encapsulated polyphenolic extract-treated non-proliferating AU565 cells, the autophagic pathway, here cytotoxic autophagy, was also induced, as judged by elevated levels of beclin-1 and LC3b. We show for the first time the anti-breast cancer activity of encapsulated polyphenolic extract of pearl millet and postulate that microencapsulation may be a useful approach for potentiating the anticancer effects of phytochemicals with limited bioavailability.
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(This article belongs to the Section Cancer Drug Development)
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Real-World Experience among Elderly Metastatic Breast Cancer Patients Treated with CDK4/6 Inhibitor-Based Therapy
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Thomas N. O’Connor, Emily Schultz, Jianxin Wang, Tracey O’Connor, Ellis Levine, Erik S. Knudsen and Agnieszka K. Witkiewicz
Cancers 2024, 16(9), 1749; https://doi.org/10.3390/cancers16091749 - 30 Apr 2024
Abstract
The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320
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The largest portion of breast cancer patients diagnosed after 70 years of age present with hormone receptor-positive (HR+) breast cancer subtypes. Cyclin-dependent kinase (CDK) 4/6 inhibitor treatment, in conjunction with endocrine therapy, has become standard-of-care for metastatic HR+ breast cancer. In total, 320 patients with metastatic breast cancer receiving CDK4/6 inhibitor combined with fulvestrant or an aromatase inhibitor were enrolled in an ongoing observational study or were included in an IRB-approved retrospective study. All patients receiving CDK4/6 inhibitor-based therapy that were ≥70 years of age (n = 111) displayed prolonged progression-free survival (27.6 months) as compared to patients <70 years of age (n = 209, 21.1 months, HR = 1.38, p < 0.05). Specifically, patients receiving a CDK4/6 inhibitor with an aromatase inhibitor who were ≥70 years of age (n = 79) displayed exceptionally prolonged progression-free survival (46.0 months) as compared to patients receiving the same treatment who were <70 years of age (n = 161, 21.8 months, HR = 1.71, p < 0.01). However, patients ≥70 years of age also experienced more frequent adverse responses to CDK4/6 inhibitor-based treatment leading to dose reduction, hold, or discontinuation than the younger cohort (69% and 53%, respectively). Treatment strategies that may decrease toxicity without affecting efficacy (such as dose titration) are worth further exploration.
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(This article belongs to the Special Issue The Long Reach of the Retinoblastoma Tumor Suppressor Pathway)
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Programmed Death Ligand-1 and Tumor Burden Score Dictate Treatment Responses in Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma
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Ming-Yu Lien, Chih-Chun Wang, Tzer-Zen Hwang, Ching-Yun Hsieh, Chuan-Chien Yang, Chien-Chung Wang, Ching-Feng Lien, Yu-Chen Shih, Shyh-An Yeh and Meng-Che Hsieh
Cancers 2024, 16(9), 1748; https://doi.org/10.3390/cancers16091748 - 30 Apr 2024
Abstract
Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden
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Background: The significance of tumor burden for survival is unknown for patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The purpose of our study was to evaluate the prognostic impact of programmed death ligand-1 (PD-L1) and tumor burden score (TBS) in patients with R/M HNSCC. Patients and Methods: R/M HNSCC patients who were treated with cisplatin, 5-fluorouracil plus cetuximab (EPF) or pembrolizumab (PPF) as first-line treatment were included in our study. PD-L1 and TBS were estimated and correlated with treatment responses. Kaplan–Meier curves were plotted for outcomes estimation. Results: A total of 252 R/M HNSCC patients were included, with 126 high tumor burden (HTB) and 126 low tumor burden (LTB) patients. Median progression-free survival (PFS) was 7.1 months in LTB and 3.9 months in HTB (p < 0.001) and median overall survival (OS) was 14.2 months in LTB and 9.2 months in HTB (p = 0.001). Patients with LTB had better PFS and OS than those with HTB independent of PD-L1 status. Subgroup analysis showed HTB patients treated with EPF had better survival than those treated with PPF, regardless of PD-L1 expression. For LTB PD-L1 positive patients, there was a longer survival with PPF than EPF, while for LTB PD-L1 negative patients, survival was similar between PPF and EPF. Multivariate analysis exhibited that tumor burden was significantly correlated with OS. Conclusions: Tumor burden is significantly correlated with survival in patients with R/M HNSCC. PD-L1 and TBS should be taken into consideration to determine first-line treatment.
Full article
(This article belongs to the Special Issue Head and Neck Cancers—Novel Approaches and Future Outlook)
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Recent Progress in Treatment for HER2-Positive Advanced Gastric Cancer
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Takeshi Kawakami and Kentaro Yamazaki
Cancers 2024, 16(9), 1747; https://doi.org/10.3390/cancers16091747 - 30 Apr 2024
Abstract
Human epidermal receptor (HER) 2-positive advanced gastric cancer is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. Although combination therapy with trastuzumab and chemotherapy provides meaningful survival benefit, clinical trials targeting HER2 have failed to demonstrate clinical
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Human epidermal receptor (HER) 2-positive advanced gastric cancer is one of the major subtypes of gastric cancer, accounting for ~20% of all cases. Although combination therapy with trastuzumab and chemotherapy provides meaningful survival benefit, clinical trials targeting HER2 have failed to demonstrate clinical benefits in first- or subsequent-line treatment. Trastuzumab deruxtecan, an antibody–drug conjugate, has shown positive results even in later-line treatment and has become new standard treatment. In first-line therapy, combination therapy with pembrolizumab and trastuzumab plus chemotherapy demonstrated a dramatic response rate. Therefore, the FDA rapidly approved it without waiting for the results of survival time. The emergence of combination therapy including immunotherapy with HER2-targeting agents and the development of HER2 targeting agents with or without immunotherapy have been advancing for treating HER2-positive gastric cancer. In this review, we will discuss the current status of treatment development and future perspectives for HER2-positive gastric cancer.
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(This article belongs to the Special Issue Feature Review Papers on Advanced Gastric Cancer)
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Bovine Meat and Milk Factor-like Sequences Are Frequently Detected in Renal Cell Carcinoma Tissues
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Ghalib Mobaraki, Shuai Shi, Kim M. Smits, Kim Severens, Kim Lommen, Dorit Rennspiess, Emil Chteinberg, Véronique Winnepenninckx, Iryna Samarska, Faisal Klufah and Axel zur Hausen
Cancers 2024, 16(9), 1746; https://doi.org/10.3390/cancers16091746 - 29 Apr 2024
Abstract
Previous studies have indicated a potential role of diet in the pathogenesis of renal cell carcinoma (RCC). Recently, circular bovine meat and milk factor (BMMF) DNAs have been identified in peritumoral tissues of human colon and breast cancers. Here, we investigated the prevalence
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Previous studies have indicated a potential role of diet in the pathogenesis of renal cell carcinoma (RCC). Recently, circular bovine meat and milk factor (BMMF) DNAs have been identified in peritumoral tissues of human colon and breast cancers. Here, we investigated the prevalence of the DNA of these novel human pathogenic infectious agents in RCC and adjacent peritumoral renal tissues. DNA was extracted from formalin-fixed and paraffin-embedded (FFPE) RCC and peritumoral kidney tissues, including a test (n = 11) and a validation (n = 152) collection. BMMF1 and BMMF2 consensus primers were designed to screen for the presence of BMMF1- and BMMF2-like DNA. In addition, BMMF-specific PCR was performed on selected cases to test for the presence of additional regions of BMMF1 and BMMF2 genomes. A reference collection of hepatocellular carcinomas (HCCs; n = 60) and adjacent peritumoral liver tissues (n = 50) was also included. Our results demonstrated that BMMF1 and BMMF2 DNAs are frequently found in human RCC tissues and are particularly more prevalent in peritumoral kidney tissues. Of note, BMMF1 and BMMF2 genotype heterogeneity was higher in peritumoral kidney tissues compared to RCC tissues. This is the first study to directly test human FFPE tissues for BMMF1- and BMMF2-like DNA using consensus PCR and demonstrate BMMF DNA in neoplastic and peritumoral kidney tissues. The findings are in line with the recently proposed indirect etiopathogenetic role of BMMFs in, e.g., colorectal carcinogenesis. Follow-up studies are needed to explore the potential role of BMMFs in the etiopathogenesis of RCC.
Full article
(This article belongs to the Section Methods and Technologies Development)
Open AccessArticle
Incident Cancer Risk in Patients with Incident Type 2 Diabetes Mellitus in Hungary (Part 1)
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Zsolt Abonyi-Tóth, György Rokszin, Ibolya Fábián, Zoltán Kiss, György Jermendy, Péter Kempler, Csaba Lengyel, István Wittmann, Gergő A. Molnár and Gábor Sütő
Cancers 2024, 16(9), 1745; https://doi.org/10.3390/cancers16091745 - 29 Apr 2024
Abstract
(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed
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(1) Background: Patients with type 2 diabetes mellitus (T2DM) are at higher risk of cancer but how these two diseases associate is still debated. The goal of this study was the assessment of the overall incidence of cancer among patients with newly diagnosed T2DM in Hungary. (2) Methods: A nationwide, retrospective, longitudinal study was performed using a Hungarian database. After exclusion of cases of age < 18 years, with gestational diabetes, with polycystic ovary syndrome, and with type 1 and prevalent type 2 diabetes mellitus, the incident T2DM (approx. 50,000 cases yearly) and for comparison, the diabetes-free Hungarian adult population (approx. 7,000,000 cases yearly) was included in the study. The primary endpoints were the overall and site-specific incidence and annual percentage change of the incidence of cancer in both populations. (3) Results: The overall incidence of cancer in patients amounted to 29.4/1000 and 6.6/1000 with or without T2DM, respectively, and the OR (95%CI) of cancer of the T2DM group was 4.32 (4.14–4.53), p < 0.0001. The risk of having cancer was age dependent. The incidence of cancer was declining in the non-diabetic but was unchanged in the T2DM population. The average lag time of diagnosing cancer after the detection of T2DM was 3.86 months. (4) Conclusions: Incident T2DM is associated with a significantly higher overall risk of incident cancer, with a reverse correlation of age. Newly registered T2DM patients were suggested to be screened for cancer within 6 months.
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(This article belongs to the Special Issue Cancer and Diabetes: What Connections Lie between Them?)
Open AccessArticle
Evolution of Complexity of Palliative Care Needs and Patient Profiles According to the PALCOM Scale (Part Two): Pooled Analysis of the Cohorts for the Development and Validation of the PALCOM Scale in Advanced Cancer Patients
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Albert Tuca, Margarita Viladot, Gemma Carrera, Lucia Llavata, Carmen Barrera, Manoli Chicote, Javier Marco-Hernández, Joan Padrosa, Carles Zamora-Martínez, Ignacio Grafia, Anais Pascual, Carme Font and Elena Font
Cancers 2024, 16(9), 1744; https://doi.org/10.3390/cancers16091744 - 29 Apr 2024
Abstract
Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialized multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains developed in 2018 and validated in 2023 to identify
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Introduction: Identifying the complexity of palliative care needs is a key aspect of referral to specialized multidisciplinary early palliative care (EPC) teams. The PALCOM scale is an instrument consisting of five multidimensional assessment domains developed in 2018 and validated in 2023 to identify the level of complexity in patients with advanced cancer. (1) Objectives: The main objective of this study was to determine the degree of instability (likelihood of level change or death), health resource consumption and the survival of patients according to the level of palliative complexity assigned at the baseline visit during a 6-month follow-up. (2) Method: An observational, prospective, multicenter study was conducted using pooled data from the development and validation cohort of the PALCOM scale. The main outcome variables were as follows: (a) instability ratio (IR), defined as the probability of level change or death; (b) emergency department visits; (c) days of hospitalization; (d) hospital death; (e) survival. All the variables were analyzed monthly according to the level of complexity assigned at the baseline visit. (3) Results: A total of 607 patients with advanced cancer were enrolled. According to the PALCOM scale, 20% of patients were classified as low complexity, 50% as medium and 30% as high complexity. The overall IR was 45% in the low complexity group, 68% in the medium complexity group and 78% in the high complexity group (p < 0.001). No significant differences in mean monthly emergency department visits (0.2 visits/ patient/month) were observed between the different levels of complexity. The mean number of days spent in hospital per month was 1.5 in the low complexity group, 1.8 in the medium complexity group and 3.2 in the high complexity group (p < 0.001). The likelihood of in-hospital death was significantly higher in the high complexity group (29%) compared to the medium (16%) and low (8%) complexity groups (p < 0.001). Six-month survival was significantly lower in the high complexity group (24%) compared to the medium (37%) and low (57%) complexity groups (p < 0.001). Conclusion: According to the PALCOM scale, more complex cases are associated with greater instability and use of hospital resources and lower survival. The data also confirm that the PALCOM scale is a consistent and useful tool for describing complexity profiles, targeting referrals to the EPC and managing the intensity of shared care.
Full article
(This article belongs to the Section Cancer Survivorship and Quality of Life)
Open AccessArticle
Quantitative Assessment of Tumor Contact with Neurogenic Zones and Its Effects on Survival: Insights beyond Traditional Predictors
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Kirsten Jung, Johanna Kempter, Georg Prokop, Tim Herrmann, Michael Griessmair, Su-Hwan Kim, Claire Delbridge, Bernhard Meyer, Denise Bernhardt, Stephanie E. Combs, Claus Zimmer, Benedikt Wiestler, Friederike Schmidt-Graf and Marie-Christin Metz
Cancers 2024, 16(9), 1743; https://doi.org/10.3390/cancers16091743 - 29 Apr 2024
Abstract
So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate
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So far, the cellular origin of glioblastoma (GBM) needs to be determined, with prevalent theories suggesting emergence from transformed endogenous stem cells. Adult neurogenesis primarily occurs in two brain regions: the subventricular zone (SVZ) and the subgranular zone (SGZ) of the hippocampal dentate gyrus. Whether the proximity of GBM to these neurogenic niches affects patient outcome remains uncertain. Previous studies often rely on subjective assessments, limiting the reliability of those results. In this study, we assessed the impact of GBM’s relationship with the cortex, SVZ and SGZ on clinical variables using fully automated segmentation methods. In 177 glioblastoma patients, we calculated optimal cutpoints of minimal distances to the SVZ and SGZ to distinguish poor from favorable survival. The impact of tumor contact with neurogenic zones on clinical parameters, such as overall survival, multifocality, MGMT promotor methylation, Ki-67 and KPS score was also examined by multivariable regression analysis, chi-square test and Mann–Whitney-U. The analysis confirmed shorter survival in tumors contacting the SVZ with an optimal cutpoint of 14 mm distance to the SVZ, separating poor from more favorable survival. In contrast, tumor contact with the SGZ did not negatively affect survival. We did not find significant correlations with multifocality or MGMT promotor methylation in tumors contacting the SVZ, as previous studies discussed. These findings suggest that the spatial relationship between GBM and neurogenic niches needs to be assessed differently. Objective measurements disprove prior assumptions, warranting further research on this topic.
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(This article belongs to the Section Cancer Survivorship and Quality of Life)
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Long-Term Results of Stereotactic Radiotherapy in Patients with at Least 10 Brain Metastases at Diagnosis
by
Rémy Kinj, Andreas Felix Hottinger, Till Tobias Böhlen, Mahmut Ozsahin, Véronique Vallet, Vincent Dunet, Hasna Bouchaab, Solange Peters, Constantin Tuleasca, Jean Bourhis and Luis Schiappacasse
Cancers 2024, 16(9), 1742; https://doi.org/10.3390/cancers16091742 - 29 Apr 2024
Abstract
Purpose: to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis. Methods: This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could
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Purpose: to evaluate an SRT approach in patients with at least 10 lesions at the time of BM initial diagnosis. Methods: This is a monocentric prospective cohort of patients treated by SRT, followed by a brain MRI every two months. Subsequent SRT could be delivered in cases of new BMs during follow-up. The main endpoints were local control rate (LCR), overall survival (OS), and strategy success rate (SSR). Acute and late toxicity were evaluated. Results: Seventy patients were included from October 2014 to January 2019, and the most frequent primary diagnosis was non-small-cell lung cancer (N = 36, 51.4%). A total of 1174 BMs were treated at first treatment, corresponding to a median number of 14 BMs per patient. Most of the patients (N = 51, 72.6%) received a single fraction of 20–24 Gy. At 1 year, OS was 62.3%, with a median OS of 19.2 months, and SSR was 77.8%. A cumulative number of 1537 BM were treated over time, corresponding to a median cumulative number of 16 BM per patient. At 1-year, the LCR was 97.3%, with a cumulative incidence of radio-necrosis of 2.1% per lesion. Three patients (4.3%) presented Grade 2 toxicity, and there was no Grade ≥ 3 toxicity. The number of treated BMs and the treatment volume did not influence OS or SSR (p > 0.05). Conclusions: SRT was highly efficient in controlling the BM, with minimal side effects. In this setting, an SRT treatment should be proposed even in patients with ≥10 BMs at diagnosis.
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(This article belongs to the Special Issue Stereotactic Radiotherapy in Tumor Ablation (Volume II))
Open AccessReview
Gastric Cancer Surgery: Balancing Oncological Efficacy against Postoperative Morbidity and Function Detriment
by
Andrianos Tsekrekos, Yasuhiro Okumura, Ioannis Rouvelas and Magnus Nilsson
Cancers 2024, 16(9), 1741; https://doi.org/10.3390/cancers16091741 - 29 Apr 2024
Abstract
Significant progress has been made in the surgical management of gastric cancer over the years, and previous discrepancies in surgical practice between different parts of the world have gradually lessened. A transition from the earlier period of progressively more extensive surgery to the
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Significant progress has been made in the surgical management of gastric cancer over the years, and previous discrepancies in surgical practice between different parts of the world have gradually lessened. A transition from the earlier period of progressively more extensive surgery to the current trend of a more tailored and evidence-based approach is clear. Prophylactic resection of adjacent anatomical structures or neighboring organs and extensive lymph node dissections that were once assumed to increase the chances of long-term survival are now performed selectively. Laparoscopic gastrectomy has been widely adopted and its indications have steadily expanded, from early cancers located in the distal part of the stomach, to locally advanced tumors where total gastrectomy is required. In parallel, function-preserving surgery has also evolved and now constitutes a valid option for early gastric cancer. Pylorus-preserving and proximal gastrectomy have improved the postoperative quality of life of patients, and sentinel node navigation surgery is being explored as the next step in the process of further refining the minimally invasive concept. Moreover, innovative techniques such as indocyanine green fluorescence imaging and robot-assisted gastrectomy are being introduced in clinical practice. These technologies hold promise for enhancing surgical precision, ultimately improving the oncological and functional outcomes.
Full article
(This article belongs to the Special Issue Gastric Cancer: Evolving Landscape and Emerging Therapies)
Open AccessArticle
The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults
by
Zhi-Feng Shi, Kay Ka-Wai Li, Anthony Pak-Yin Liu, Nellie Yuk-Fei Chung, Sze-Ching Wong, Hong Chen, Peter Yat-Ming Woo, Danny Tat-Ming Chan, Ying Mao and Ho-Keung Ng
Cancers 2024, 16(9), 1740; https://doi.org/10.3390/cancers16091740 - 29 Apr 2024
Abstract
Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the
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Pediatric brain tumors are often noted to be different from their adult counterparts in terms of molecular features. Primary CNS lymphomas (PCNSLs) are mostly found in elderly adults and are uncommon in children and teenagers. There has only been scanty information about the molecular features of PCNSLs at a young age. We examined PCNSLs in 34 young patients aged between 7 and 39 years for gene rearrangements of BCl2, BCL6, CCND1, IRF4, IGH, IGL, IGK, and MYC, homozygous deletions (HD) of CDKN2A, and HLA by FISH. Sequencing was performed using WES, panel target sequencing, or Sanger sequencing due to the small amount of available tissues. The median OS was 97.5 years and longer than that for older patients with PCNSLs. Overall, only 14 instances of gene rearrangement were found (5%), and patients with any gene rearrangement were significantly older (p = 0.029). CDKN2A HD was associated with a shorter OS (p < 0.001). Only 10/31 (32%) showed MYD88 mutations, which were not prognostically significant, and only three of them were L265P mutations. CARD11 mutations were found in 8/24 (33%) cases only. Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.
Full article
(This article belongs to the Special Issue Molecular Pathology of Brain Tumors)
Open AccessReview
Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma
by
Kuo-Shyang Jeng, Chiung-Fang Chang, Yuk-Ming Tsang, I-Shyan Sheen and Chi-Juei Jeng
Cancers 2024, 16(9), 1739; https://doi.org/10.3390/cancers16091739 - 29 Apr 2024
Abstract
HCC remains one of the leading causes of cancer-related death globally. The main challenges in treatments of hepatocellular carcinoma (HCC) primarily arise from high rates of postoperative recurrence and the limited efficacy in treating advanced-stage patients. Various signaling pathways involved in HCC have
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HCC remains one of the leading causes of cancer-related death globally. The main challenges in treatments of hepatocellular carcinoma (HCC) primarily arise from high rates of postoperative recurrence and the limited efficacy in treating advanced-stage patients. Various signaling pathways involved in HCC have been reported. Among them, the Sonic hedgehog (SHH) signaling pathway is crucial. The presence of SHH ligands is identified in approximately 60% of HCC tumor tissues, including tumor nests. PTCH-1 and GLI-1 are detected in more than half of HCC tissues, while GLI-2 is found in over 84% of HCC tissues. The SHH signaling pathway (including canonical and non-canonical) is involved in different aspects of HCC, including hepatocarcinogenesis, tumor growth, tumor invasiveness, progression, and migration. The SHH signaling pathway also contributes to recurrence, metastasis, modulation of the cancer microenvironment, and sustaining cancer stem cells. It also affects the resistance of HCC cells to chemotherapy, target therapy, and radiotherapy. Reappraisal of the roles of the SHH signaling pathway in HCC may trigger some novel therapies for HCC.
Full article
(This article belongs to the Section Molecular Cancer Biology)
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Open AccessArticle
The Impact of the COVID-19 Pandemic on Time to Treatment in Surgical Oncology: A National Registry Study in the Netherlands
by
Roos M. G. van Vuren, Yester F. Janssen, Rianne N. M. Hogenbirk, Michelle R. de Graaff, Rinske van den Hoek, Schelto Kruijff, David J. Heineman, Willemijn Y. van der Plas and Michel W. J. M. Wouters
Cancers 2024, 16(9), 1738; https://doi.org/10.3390/cancers16091738 - 29 Apr 2024
Abstract
To avoid delay in oncological treatment, a 6-weeks norm for time to treatment has been agreed on in the Netherlands. However, the impact of the COVID-19 pandemic on health systems resulted in reduced capacity for regular surgical care. In this study, we investigated
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To avoid delay in oncological treatment, a 6-weeks norm for time to treatment has been agreed on in the Netherlands. However, the impact of the COVID-19 pandemic on health systems resulted in reduced capacity for regular surgical care. In this study, we investigated the impact of the COVID-19 pandemic on time to treatment in surgical oncology in the Netherlands. Methods: A population-based analysis of data derived from five surgical audits, including patients who underwent surgery for lung cancer, colorectal cancer, upper gastro-intestinal, and hepato-pancreato-biliary (HPB) malignancies, was performed. The COVID-19 cohort of 2020 was compared to the historic cohorts of 2018 and 2019. Primary endpoints were time to treatment initiation and the proportion of patients whose treatment started within 6 weeks. The secondary objective was to evaluate the differences in characteristics and tumour stage distribution between patients treated before and during the COVID-19 pandemic. Results: A total of 14,567 surgical cancer patients were included in this study, of these 3292 treatments were started during the COVID-19 pandemic. The median time to treatment decreased during the pandemic (26 vs. 27 days, p < 0.001) and the proportion of patients whose treatment started within 6 weeks increased (76% vs. 73%, p < 0.001). In a multivariate logistic regression analysis, adjusting for patient characteristics, no significant difference in post-operative outcomes between patients who started treatment before or after 6 weeks was found. Overall, the number of procedures performed per week decreased by 8.1% during the pandemic. This reduction was most profound for patients with stage I lung carcinoma and colorectal carcinoma. There were fewer patients with pulmonary comorbidities in the pandemic cohort (11% vs. 13%, p = 0.003). Conclusions: Despite pressure on the capacity of the healthcare system during the COVID-19 pandemic, a larger proportion of surgical oncological patients started treatment within six weeks, possibly due to prioritisation of cancer care and reductions in elective procedures. However, during the pandemic, a decrease in the number of surgical oncological procedures performed in the Netherlands was observed, especially for patients with stage I disease.
Full article
(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)
Open AccessArticle
High Serum Levels of CCL20 Are Associated with Recurrence and Unfavorable Overall Survival in Advanced Melanoma Patients Receiving Immunotherapy
by
Julian Kött, Inka Lilott Hoehne, Isabel Heidrich, Noah Zimmermann, Kim-Lea Reese, Tim Zell, Glenn Geidel, Alessandra Rünger, Stefan W. Schneider, Klaus Pantel, Daniel J. Smit and Christoffer Gebhardt
Cancers 2024, 16(9), 1737; https://doi.org/10.3390/cancers16091737 - 29 Apr 2024
Abstract
Background: Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression. Methods: In this prospective study, we analyzed the
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Background: Immune checkpoint inhibition has revolutionized melanoma therapy, but many patients show primary or secondary resistance. Biomarkers are, therefore, urgently required to predict response prior to the initiation of therapy and to monitor disease progression. Methods: In this prospective study, we analyzed the serum C-C motif chemokine ligand 20 (CCL20) concentration using an enzyme-linked immunosorbent assay. Blood was obtained at baseline before the initiation of immunotherapy with anti-PD-1 monotherapy or Nivolumab and Ipilimumab in advanced melanoma patients (stages III and IV) enrolled at the University Medical Center Hamburg-Eppendorf. The CCL20 levels were correlated with clinico-pathological parameters and disease-related outcomes. Results: An increased C-C motif chemokine ligand 20 (CCL20) concentration (≥0.34 pg/mL) at baseline was associated with a significantly impaired progression-free survival (PFS) in the high-CCL20 group (3 months (95% CI: 2–6 months) vs. 11 months (95% CI: 6–26 months)) (p = 0.0033) and could be identified as an independent negative prognostic factor for PFS in univariate (Hazard Ratio (HR): 1.98, 95% CI 1.25–3.12, p = 0.004) and multivariate (HR: 1.99, 95% CI 1.21–3.29, p = 0.007) Cox regression analysis, which was associated with a higher risk than S100 (HR: 1.74). Moreover, high CCL20 levels were associated with impaired overall survival (median OS not reached for low-CCL20 group, p = 0.042) with an HR of 1.85 (95% CI 1.02–3.37, p = 0.043) in univariate analysis similar to the established prognostic marker S100 (HR: 1.99, 95% CI: 1.02–3.88, p = 0.043). Conclusions: CCL20 may represent a novel blood-based biomarker for the prediction of resistance to immunotherapy that can be used in combination with established strong clinical predictors (e.g., ECOG performance score) and laboratory markers (e.g., S100) in advanced melanoma patients. Future prospective randomized trials are needed to establish CCL20 as a liquid biopsy-based biomarker in advanced melanoma.
Full article
(This article belongs to the Special Issue Novel Developments on Skin Cancer Diagnostics and Treatment)
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