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
Monitoring Response and Resistance to Treatment in Chronic Lymphocytic Leukemia
Cancers 2024, 16(11), 2049; https://doi.org/10.3390/cancers16112049 - 28 May 2024
Abstract
The recent evolution in chronic lymphocytic leukemia (CLL) targeted therapies led to a progressive change in the way clinicians manage the goals of treatment and evaluate the response to treatment in respect to the paradigm of the chemoimmunotherapy era. Continuous therapies with BTK
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The recent evolution in chronic lymphocytic leukemia (CLL) targeted therapies led to a progressive change in the way clinicians manage the goals of treatment and evaluate the response to treatment in respect to the paradigm of the chemoimmunotherapy era. Continuous therapies with BTK inhibitors achieve prolonged and sustained control of the disease. On the other hand, venetoclax and anti-CD20 monoclonal antibodies or, more recently, ibrutinib plus venetoclax combinations, given for a fixed duration, achieve undetectable measurable residual disease (uMRD) in the vast majority of patients. On these grounds, a time-limited MRD-driven strategy, a previously unexplored scenario in CLL, is being attempted. On the other side of the spectrum, novel genetic and non-genetic mechanisms of resistance to targeted treatments are emerging. Here we review the response assessment criteria, the evolution and clinical application of MRD analysis and the mechanisms of resistance according to the novel treatment strategies within clinical trials. The extent to which this novel evidence will translate in the real-life management of CLL patients remains an open issue to be addressed.
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(This article belongs to the Section Cancer Therapy)
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Utility of a Multi-Marker Panel with Ultrasound for Enhanced Classification of Adnexal Mass
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Andrew N. Stephens, Simon J. Hobbs, Sung-Woog Kang, Martin K. Oehler, Tom W. Jobling and Richard Allman
Cancers 2024, 16(11), 2048; https://doi.org/10.3390/cancers16112048 - 28 May 2024
Abstract
Pre-surgical clinical assessment of an adnexal mass typically relies on transvaginal ultrasound for comprehensive morphological assessment, with further support provided by biomarker measurements and clinical evaluation. Whilst effective for masses that are obviously benign or malignant, a large proportion of masses remain sonographically
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Pre-surgical clinical assessment of an adnexal mass typically relies on transvaginal ultrasound for comprehensive morphological assessment, with further support provided by biomarker measurements and clinical evaluation. Whilst effective for masses that are obviously benign or malignant, a large proportion of masses remain sonographically indeterminate at surgical referral. As a consequence, post-surgical diagnoses of benign disease can outnumber malignancies up to 9-fold, while less than 50% of cancer cases receive a primary referral to a gynecological oncology specialist. We recently described a blood biomarker signature (multi-marker panel—MMP) that differentiated patients with benign from malignant ovarian disease with high accuracy. In this study, we have examined the use of the MMP, both individually and in combination with transvaginal ultrasound, as an alternative tool to CA-125 for enhanced decision making in the pre-surgical referral process.
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(This article belongs to the Special Issue New Challenges in Gynaecological Cancers Diagnosis and Treatment)
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Biological Insights and Radiation–Immuno–Oncology Developments in Primary and Secondary Brain Tumors
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Fabiana Gregucci, Kathryn Beal, Jonathan P. S. Knisely, Paul Pagnini, Alba Fiorentino, Elisabetta Bonzano, Claire I. Vanpouille-Box, Babacar Cisse, Susan C. Pannullo, Philip E. Stieg and Silvia C. Formenti
Cancers 2024, 16(11), 2047; https://doi.org/10.3390/cancers16112047 - 28 May 2024
Abstract
Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts,
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Malignant central nervous system (CNS) cancers include a group of heterogeneous dis-eases characterized by a relative resistance to treatments and distinguished as either primary tumors arising in the CNS or secondary tumors that spread from other organs into the brain. Despite therapeutic efforts, they often cause significant mortality and morbidity across all ages. Radiotherapy (RT) remains the main treatment for brain cancers, improving associated symptoms, improving tumor control, and inducing a cure in some. However, the ultimate goal of cancer treatment, to improve a patient’s survival, remains elusive for many CNS cancers, especially primary tumors. Over the years, there have thus been many preclinical studies and clinical trials designed to identify and overcome mechanisms of resistance to improve outcomes after RT and other therapies. For example, immunotherapy delivered concurrent with RT, especially hypo-fractionated stereotactic RT, is synergistic and has revolutionized the clinical management and outcome of some brain tumors, in particular brain metastases (secondary brain tumors). However, its impact on gliomas, the most common primary malignant CNS tumors, remains limited. In this review, we provide an overview of radioresistance mechanisms, the emerging strategies to overcome radioresistance, the role of the tumor microenviroment (TME), and the selection of the most significant results of radiation–immuno–oncological investigations. We also identify novel therapeutic opportunities in primary and secondary brain tumors with the purpose of elucidating current knowledge and stimulating further research to improve tumor control and patients’ survival.
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(This article belongs to the Special Issue Advances in Radiation Immuno-Oncology: Progress at the Interface of Radiation Oncology and Immunotherapy—A Themed Issue in Honor of Prof. Dr. Gabriele Multhoff)
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Factors Associated with Primary Liver Cancer Survival in a Southern Italian Setting in a Changing Epidemiological Scenario
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Sergio Mazzola, Martina Vittorietti, Santo Fruscione, Daniele Domenico De Bella, Alessandra Savatteri, Miriam Belluzzo, Daniela Ginevra, Alice Gioia, Davide Costanza, Maria Domenica Castellone, Claudio Costantino, Maurizio Zarcone, Barbara Ravazzolo, Giorgio Graziano, Rita Mannino, Rosalba Amodio, Vito Di Marco, Francesco Vitale and Walter Mazzucco
Cancers 2024, 16(11), 2046; https://doi.org/10.3390/cancers16112046 - 28 May 2024
Abstract
A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male),
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A retrospective observational study utilising cancer incidence data from a population-based registry investigated determinants affecting primary liver cancer survival in a southern Italian region with high hepatitis viral infection rates and obesity prevalence. Among 2687 patients diagnosed between 2006 and 2019 (65.3% male), a flexible hazard-based regression model revealed factors influencing 5-year survival rates. High deprivation levels [HR = 1.41 (95%CI = 1.15–1.76); p < 0.001], poor access to care [HR = 1.99 (95%IC = 1.70–2.35); p < 0.0001], age between 65 and 75 [HR = 1.48 (95%IC = 1.09–2.01); p < 0.05] or >75 [HR = 2.21 (95%CI = 1.62–3.01); p < 0.0001] and residing in non-urban areas [HR = 1.35 (95%CI = 1.08–1.69); p < 0.01] were associated with poorer survival estimates. While deprivation appeared to be a risk factor for primary liver cancer patients residing within the urban area, the geographic distance from specialised treatment centres emerged as a potential determinant of lower survival estimates for residents in the non-urban areas. After balancing the groups of easy and poor access to care using a propensity score approach, poor access to care and a lower socioeconomic status resulted in potentially having a negative impact on primary liver cancer survival, particularly among urban residents. We emphasise the need to interoperate cancer registries with other data sources and to deploy innovative digital solutions to improve cancer prevention.
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(This article belongs to the Section Cancer Epidemiology and Prevention)
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Open AccessReview
Pharmacologic Management of End-of-Life Delirium: Translating Evidence into Practice
by
David Hui, Shao-Yi Cheng and Carlos Eduardo Paiva
Cancers 2024, 16(11), 2045; https://doi.org/10.3390/cancers16112045 - 28 May 2024
Abstract
End-of-life delirium affects a vast majority of patients before death. It is highly distressing and often associated with restlessness or agitation. Unlike delirium in other settings, it is considered irreversible, and non-pharmacologic measures may be less feasible. The objective of this review is
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End-of-life delirium affects a vast majority of patients before death. It is highly distressing and often associated with restlessness or agitation. Unlike delirium in other settings, it is considered irreversible, and non-pharmacologic measures may be less feasible. The objective of this review is to provide an in-depth discussion of the clinical trials on delirium in the palliative care setting, with a particular focus on studies investigating pharmacologic interventions for end-of-life delirium. To date, only six randomized trials have examined pharmacologic options in palliative care populations, and only two have focused on end-of-life delirium. These studies suggest that neuroleptics and benzodiazepines may be beneficial for the control of the terminal restlessness or agitation associated with end-of-life delirium. However, existing studies have significant methodologic limitations. Further studies are needed to confirm these findings and examine novel therapeutic options to manage this distressing syndrome.
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(This article belongs to the Special Issue Advances in Supportive and Palliative Care in Cancer)
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Chronic Stress Related to Cancer Incidence, including the Role of Metabolic Syndrome Components
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An Thanh Pham, Boukje A. C. van Dijk, Eline S. van der Valk, Bert van der Vegt, Elisabeth F. C. van Rossum and Geertruida H. de Bock
Cancers 2024, 16(11), 2044; https://doi.org/10.3390/cancers16112044 - 28 May 2024
Abstract
Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed
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Epidemiological results on the link between chronic stress and cancer initiation have been inconsistent. This study examined the relation between chronic biological stress, indicated as hair cortisol (HairF) and hair cortisone (HairE), and cancer incidence, adjusting for metabolic syndrome (MetS) components. We analyzed HairF and HairE samples from 6341 participants from the population-based cohort Lifelines in 2014. A linkage with the Dutch Nationwide Pathology Databank (Palga) provided the cancer incidence from 2015 to 2021. The association between dichotomized HairF and log-transformed HairE (LogHairE) and cancer incidence was estimated using Cox regression. MetS components were evaluated as confounders or moderators. Of the 2776 participants with known HairF levels and no cancer history, 238 developed cancer. The HairF level did not predict cancer incidence (HR: 0.993, 95%CI: 0.740–1.333). No confounders or moderators were identified. Among the 4699 participants with known HairE levels and no cancer history, 408 developed cancer. There was no association between LogHairE and cancer incidence (HR: 1.113, 95%CI: 0.738–1.678). When including age as a confounder and gender as a moderator, LogHairE was statistically significantly associated with cancer incidence (HR: 6.403, 95%CI: 1.110–36.92). In a population-based cohort, chronic biological stress, measured by HairE, was associated with cancer incidence, after controlling for age and gender.
Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
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Cervical Intraepithelial Neoplasia Grade 3 (CIN3) in Women Younger than 30 Years Was Significantly Associated with HPV16/18 Genotypes
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Maria Teresa Bruno, Marco Marzio Panella, Gaetano Valenti, Zaira Ruggeri, Francesco Sgalambro, Salvatore Reina and Liliana Mereu
Cancers 2024, 16(11), 2043; https://doi.org/10.3390/cancers16112043 - 28 May 2024
Abstract
Background. The objective of the present study is to investigate the age-specific distribution of HPV genotypes in CIN3 lesions in screened unvaccinated women. These data are essential to optimize current and future screening programs. Methods. A multicenter retrospective study was conducted. A total
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Background. The objective of the present study is to investigate the age-specific distribution of HPV genotypes in CIN3 lesions in screened unvaccinated women. These data are essential to optimize current and future screening programs. Methods. A multicenter retrospective study was conducted. A total of 408 unvaccinated women with positive histology and a high-risk HPV genotype were enrolled. Each woman at baseline had HPV DNA testing and HPV genotyping, and all women underwent targeted biopsy and/or treatment with a loop electrosurgical excision procedure (LEEP) before entering the study. We divided the genotypes into HPV16/18 and HPV non-16/18 (HPV31/33/45/35/39/51/52/58/59/66/68). Women were divided into increasing age categories: <30, 30–44, and ≥45. Results. The percentage of CIN3 associated with HPV16/18 is maximum in women under 30 years of age (85.1%), drops to 75.6% in women aged between 30 and 44 years, and up to 47.2% in women over 45 years. CIN3 in women younger than 30 years was significantly associated with HPV16/18 genotypes (p = 0). Discussion. The data from the present study suggest that the risk of CIN3 is related to the woman’s age and hr HPV genotype. The data highlight two different types of CIN3: a more frequent type, related to HPV16/18, which develops rapidly and in young women, and another, relating to non-16/18 HPV, which develops later at an advanced age and slowly, through low-grade lesions.
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(This article belongs to the Section Infectious Agents and Cancer)
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Immune Checkpoint Inhibitors in Hepatocellular Carcinoma and Their Hepatic-Related Side Effects: A Review
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Thomas M. Ruli, Jr., Ethan D. Pollack, Atul Lodh, Charles D. Evers III, Christopher A. Price and Mohamed Shoreibah
Cancers 2024, 16(11), 2042; https://doi.org/10.3390/cancers16112042 - 28 May 2024
Abstract
Primary liver cancer is one of the leading causes of cancer mortality worldwide, with hepatocellular carcinoma (HCC) being the most prevalent type of liver cancer. The prognosis of patients with advanced, unresectable HCC has historically been poor. However, with the emergence of immunotherapy,
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Primary liver cancer is one of the leading causes of cancer mortality worldwide, with hepatocellular carcinoma (HCC) being the most prevalent type of liver cancer. The prognosis of patients with advanced, unresectable HCC has historically been poor. However, with the emergence of immunotherapy, specifically immune checkpoint inhibitors (ICIs), there is reason for optimism. Nevertheless, ICIs do not come without risk, especially when administered in patients with HCC, given their potential underlying poor hepatic reserve. Given their novelty in the management of HCC, there are few studies to date specifically investigating ICI-related side effects on the liver in patients with underlying HCC. This review will serve as a guide for clinicians on ICIs’ role in the management of HCC and their potential side effect profile. There will be a discussion on ICI-related hepatotoxicity, the potential for hepatitis B and C reactivation with ICI use, the potential for the development of autoimmune hepatitis with ICI use, and the risk of gastrointestinal bleeding with ICI use. As ICIs become more commonplace as a treatment option in patients with advanced HCC, it is imperative that clinicians not only understand the mechanism of action of such agents but also understand and are able to identify hepatic-related side effects.
Full article
(This article belongs to the Special Issue Hepatocellular Carcinoma: Advances and Challenges in Research and Treatment)
Open AccessArticle
Synergistic Antitumor Activity of Talazoparib and Temozolomide in Malignant Rhabdoid Tumors
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Elena Mironova, Sebastian Molinas, Vanessa Del Pozo, Abhik M. Bandyopadhyay, Zhao Lai, Dias Kurmashev, Eric L. Schneider, Daniel V. Santi, Yidong Chen and Raushan T. Kurmasheva
Cancers 2024, 16(11), 2041; https://doi.org/10.3390/cancers16112041 - 28 May 2024
Abstract
Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1
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Malignant rhabdoid tumors (MRTs) are among the most aggressive and treatment-resistant malignancies affecting infants, originating in the kidney, brain, liver, and soft tissues. The 5-year event-free survival rate for these cancers is a mere 20%. In nearly all cases of MRT, the SMARCB1 gene (occasionally SMARCA4)—a pivotal component of the SWI/SNF chromatin remodeling complex—is homozygously deleted, although the precise etiology of these tumors remains unknown. While young patients with localized MRT generally show improved outcomes, especially those who are older and have early-stage disease, the overall prognosis remains poor despite optimal standard treatments. This highlights the urgent need for more effective treatment strategies. We investigated the antitumor activity of a PARP1 inhibitor (talazoparib, TLZ) combined with a DNA alkylating agent (temozolomide, TMZ) in MRT xenograft models. PARP1 is a widely targeted molecule in cancer treatment and, beyond its role in DNA repair, it participates in transcriptional regulation by recruiting chromatin remodeling complexes to modulate DNA accessibility for RNA polymerases. To widen the therapeutic window of the drug combination, we employed PEGylated TLZ (PEG~TLZ), which has been reported to reduce systemic toxicity through slow drug release. Remarkably, our findings indicate that five out of six MRT xenografts exhibited an objective response to PEG~TLZ+TMZ therapy. Significantly, the loss of SMARCB1 was found to confer a protective effect, correlating with higher expression levels of DNA damage and repair proteins in SMARCB1-deficient MRT cells. Additionally, we identified MGMT as a potential biomarker indicative of in vivo MRT response to PEG~TLZ+TMZ therapy. Moreover, our analysis revealed alterations in signaling pathways associated with the observed antitumor efficacy. This study presents a novel and efficacious therapeutic approach for MRT, along with a promising candidate biomarker for predicting tumor response.
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(This article belongs to the Special Issue Pediatric Cancer: From Molecular Targets to Effective Therapies)
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Single-Cell Profiling Reveals the Impact of Genetic Alterations on the Differentiation of Inflammation-Induced Murine Colon Tumors
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Ahmed H. Ghobashi, Rosie Lanzloth, Christopher A. Ladaika, Ashiq Masood and Heather M. O’Hagan
Cancers 2024, 16(11), 2040; https://doi.org/10.3390/cancers16112040 - 28 May 2024
Abstract
Genetic mutations and chronic inflammation of the colon contribute to the development of colorectal cancer (CRC). Using a murine model of inflammation-induced colon tumorigenesis, we determined how genetic mutations alter colon tumor cell differentiation. Inflammation induced by enterotoxigenic Bacteroides fragilis (ETBF) colonization of
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Genetic mutations and chronic inflammation of the colon contribute to the development of colorectal cancer (CRC). Using a murine model of inflammation-induced colon tumorigenesis, we determined how genetic mutations alter colon tumor cell differentiation. Inflammation induced by enterotoxigenic Bacteroides fragilis (ETBF) colonization of multiple intestinal neoplasia (MinApcΔ716/+) mice triggers loss of heterozygosity of Apc causing colon tumor formation. Here, we report that the addition of BRAFV600E mutation (BRAFF-V600ELgr5tm1(Cre/ERT2)CleMinApcΔ716/+, BLM) or knocking out Msh2 (Msh2LoxP/LoxPVil1-creMinApcΔ716/+, MSH2KO) in the Min model altered colon tumor differentiation. Using single-cell RNA sequencing, we uncovered the differences between BLM, Min, and MSH2KO tumors at a single-cell resolution. BLM tumors showed an increase in differentiated tumor epithelial cell lineages and a reduction in the tumor stem cell population. Interestingly, the tumor stem cell population of BLM tumors had revival colon stem cell characteristics with low WNT signaling and an increase in RevCSC marker gene expression. In contrast, MSH2KO tumors were characterized by an increased tumor stem cell population that had higher WNT signaling activity compared to Min tumors. Furthermore, overall BLM tumors had higher expression of transcription factors that drive differentiation, such as Cdx2, than Min tumors. Using RNA velocity, we identified additional potential regulators of BLM tumor differentiation such as NDRG1. The role of CDX2 and NDRG1 as putative regulators for BLM tumor cell differentiation was verified using organoids derived from BLM tumors. Our results demonstrate the critical connections between genetic mutations and cell differentiation in inflammation-induced colon tumorigenesis. Understanding such roles will deepen our understanding of inflammation-associated colon cancer.
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(This article belongs to the Section Cancer Informatics and Big Data)
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Preoperative Classification of Peripheral Nerve Sheath Tumors on MRI Using Radiomics
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Christianne Y. M. N. Jansma, Xinyi Wan, Ibtissam Acem, Douwe J. Spaanderman, Jacob J. Visser, David Hanff, Walter Taal, Cornelis Verhoef, Stefan Klein, Enrico Martin and Martijn P. A. Starmans
Cancers 2024, 16(11), 2039; https://doi.org/10.3390/cancers16112039 - 28 May 2024
Abstract
Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors prevalent in neurofibromatosis type 1 (NF1) patients, posing a significant risk of metastasis and recurrence. Current magnetic resonance imaging (MRI) imaging lacks decisiveness in distinguishing benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs,
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Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft-tissue tumors prevalent in neurofibromatosis type 1 (NF1) patients, posing a significant risk of metastasis and recurrence. Current magnetic resonance imaging (MRI) imaging lacks decisiveness in distinguishing benign peripheral nerve sheath tumors (BPNSTs) and MPNSTs, necessitating invasive biopsies. This study aims to develop a radiomics model using quantitative imaging features and machine learning to distinguish MPNSTs from BPNSTs. Clinical data and MRIs from MPNST and BPNST patients (2000–2019) were collected at a tertiary sarcoma referral center. Lesions were manually and semi-automatically segmented on MRI scans, and radiomics features were extracted using the Workflow for Optimal Radiomics Classification (WORC) algorithm, employing automated machine learning. The evaluation was conducted using a 100× random-split cross-validation. A total of 35 MPNSTs and 74 BPNSTs were included. The T1-weighted (T1w) MRI radiomics model outperformed others with an area under the curve (AUC) of 0.71. The incorporation of additional MRI scans did not enhance performance. Combining T1w MRI with clinical features achieved an AUC of 0.74. Experienced radiologists achieved AUCs of 0.75 and 0.66, respectively. Radiomics based on T1w MRI scans and clinical features show some ability to distinguish MPNSTs from BPNSTs, potentially aiding in the management of these tumors.
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(This article belongs to the Special Issue Innovations in Soft Tissue Sarcoma Diagnosis and Treatment)
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Clinical Relevance of Resection Margins in Patients with Total Laryngectomy or Laryngopharyngectomy
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Simone E. Bernard, Cornelia G. F. van Lanschot, Aniel Sewnaik, Maria A. J. de Ridder, Jose A. Hardillo, Dominiek A. Monserez, Robert J. Baatenburg de Jong and Senada Koljenović
Cancers 2024, 16(11), 2038; https://doi.org/10.3390/cancers16112038 - 28 May 2024
Abstract
Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with
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Background: Laryngeal and hypopharyngeal cancer is complex and resection margins are therefore constrained. The aim of this study was to investigate the clinical relevance of resection margins in laryngeal and hypopharyngeal surgery. Methods: A retrospective cohort study was performed for patients treated with a total laryngectomy (TL) or laryngopharyngectomy (TLP) for laryngeal or hypopharyngeal squamous cell carcinoma (LSCC and HSCC, respectively). Within the groups primary LSCC, recurrent LSCC, primary HSCC, and recurrent HSCC the relationship between the status of the resection margin according to the Royal Collage of Pathology and the recurrence and survival rates were investigated. Results: Positive resection margins were found in 54% for primary LSCC, 29% for recurrent LSCC, 62% for primary HSCC, and 44% for recurrent HSCC. For primary and recurrent LSCC, there was a linear association between total recurrence and narrowing margins (p = 0.007 resp. p = 0.008). Multivariate survival analysis for primary and recurrent LSCC showed a significantly worse disease free and disease-specific survival in case of positive margins compared to clear margins. Conclusion: Similar survival rates were recorded for close and clear margins for primary and recurrent LSCC. This may suggest that a margin > 5 mm is not clinically relevant in terms of survival. Therefore, a margin of 1–5 mm should be accepted in certain subsites. Margins < 1 mm are related to significantly worse outcomes and should be avoided.
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(This article belongs to the Section Cancer Therapy)
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Open AccessCorrection
Correction: Corsaro et al. Notch, SUMOylation, and ESR-Mediated Signalling Are the Main Molecular Pathways Showing Significantly Different Epimutation Scores between Expressing or Not Oestrogen Receptor Breast Cancer in Three Public EWAS Datasets. Cancers 2023, 15, 4109
by
Luigi Corsaro, Davide Gentilini, Luciano Calzari and Vincenzo Sandro Gambino
Cancers 2024, 16(11), 2037; https://doi.org/10.3390/cancers16112037 - 28 May 2024
Abstract
Additional Affiliation(s) [...]
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Open AccessArticle
Bimodal Effect of NKG2A Blockade on Intratumoral and Systemic CD8 T Cell Response Induced by Cancer Vaccine
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Erika Riva, Susanna Carboni, Wilma di Berardino-Besson, Mati Moyat, Elodie Belnoue, Laetitia Devy-Dimanche and Matteo Rossi
Cancers 2024, 16(11), 2036; https://doi.org/10.3390/cancers16112036 - 27 May 2024
Abstract
Immune check-point blockade (ICB) has revitalized cancer immunotherapy, showing unprecedented efficacy despite only a narrow number of indications and with limited long-term protection. Cancer vaccines are promising combination partners for ICB to widen the patient population profiting from these treatments. Therapeutic heterologous prime-boost
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Immune check-point blockade (ICB) has revitalized cancer immunotherapy, showing unprecedented efficacy despite only a narrow number of indications and with limited long-term protection. Cancer vaccines are promising combination partners for ICB to widen the patient population profiting from these treatments. Therapeutic heterologous prime-boost vaccination with KISIMATM protein vaccine and VSV-GP-TAg oncolytic virus was shown to inflame the tumor microenvironment, promoting significant infiltration of antigen-specific CD8 T cells resulting in robust antitumoral efficacy in mouse tumor models, and clinical trials are currently ongoing. Here, we report the impact of NKG2A blockade on antitumoral CD8 T cell immune response elicited by KISIMA—VSV-GP-TAg vaccination in tumor mouse models. Combination therapy significantly reduced the amount of vaccine-induced exhausted CD8 T cells infiltrating the tumor, resulting in short-term improved tumor growth control and prolonged mouse survival, while it also influenced the establishment of systemic effector memory CD8 T cell response. Taken together, these data show a compartment-dependent effect of NKG2A blockade on cancer vaccine-induced T cell immunity, increasing intratumoral T cell efficacy and attenuating the development of peripheral effector memory CD8 T cell response.
Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
Open AccessArticle
Type IX Collagen Turnover Is Altered in Patients with Solid Tumors
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Helena Port, Yi He, Morten A. Karsdal, Emilie A. Madsen, Anne-Christine Bay-Jensen, Nicholas Willumsen and Signe Holm Nielsen
Cancers 2024, 16(11), 2035; https://doi.org/10.3390/cancers16112035 - 27 May 2024
Abstract
The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs)
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The fibrotic tumor microenvironment, characterized by its intricate extracellular matrix (ECM), consists of many collagens with diverse functions and unexplored biomarker potential. Type IX collagen is a member of the low-abundance collagen family known as the fibril-associated collagen with interrupted triple helices (FACITs) and is found mostly in cartilage. Its role in the tumor microenvironment remains unexplored. To investigate the biomarker potential of a type IX collagen in cancer, an immuno-assay was developed (PRO-C9) and technical assay performance was evaluated for the assessment of serum. PRO-C9 levels were measured in serum samples from 259 patients with various solid tumor types compared to serum levels from 73 healthy controls. PRO-C9 levels were significantly elevated in patients with solid tumors including bladder, breast, colorectal, gastric, head and neck, lung, melanoma, ovarian, pancreatic, and renal compared to levels in healthy controls (p < 0.05–p < 0.0001). PRO-C9 could discriminate between patients with cancer and healthy controls, with the area under the receiver operating characteristic values ranging from 0.58 to 0.86 (p < 0.3–p < 0.0001), indicating potential diagnostic utility. This study suggests that type IX collagen turnover is altered in patients with solid tumors and demonstrates the feasibility of using PRO-C9 as a non-invasive serum-based biomarker with relevance in multiple cancer types. Furthermore, these results underscore the potential utility of PRO-C9 to better elucidate the biology of FACITs in cancers.
Full article
(This article belongs to the Special Issue New Biomarkers in Cancers (Volume II))
Open AccessReview
Hepatocellular Carcinoma: Beyond the Border of Advanced Stage Therapy
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Yusra Zarlashat, Shakil Abbas and Abdul Ghaffar
Cancers 2024, 16(11), 2034; https://doi.org/10.3390/cancers16112034 - 27 May 2024
Abstract
Hepatocellular carcinoma (HCC) is the deadliest emergent health issue around the globe. The stronger oncogenic effect, proteins, and weakened immune response are precisely linked with a significant prospect of developing HCC. Several conventional systemic therapies, antiangiogenic therapy, and immunotherapy techniques have significantly improved
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Hepatocellular carcinoma (HCC) is the deadliest emergent health issue around the globe. The stronger oncogenic effect, proteins, and weakened immune response are precisely linked with a significant prospect of developing HCC. Several conventional systemic therapies, antiangiogenic therapy, and immunotherapy techniques have significantly improved the outcomes for early-, intermediate-, and advanced-stage HCC patients, giving new hope for effective HCC management and prolonged survival rates. Innovative therapeutic approaches beyond conventional treatments have altered the landscape of managing HCC, particularly focusing on targeted therapies and immunotherapies. The advancement in HCC treatment suggested by the Food and Drug Administration is multidimensional treatment options, including multikinase inhibitors (sorafenib, lenvatinib, regorafenib, ramucirumab, and cabozantinib) and immune checkpoint inhibitors (atezolizumab, pembrolizumab, durvalumab, tremelimumab, ipilimumab, and nivolumab), in monotherapy and in combination therapy to increase life expectancy of HCC patients. This review highlights the efficacy of multikinase inhibitors and immune checkpoint inhibitors in monotherapy and combination therapy through the analysis of phase II, and III clinical trials, targeting the key molecular pathways involved in cellular signaling and immune response for the prospective treatment of advanced and unresectable HCC and discusses the upcoming combinations of immune checkpoint inhibitors-tyrosine kinase inhibitors and immune checkpoint inhibitors-vascular endothelial growth factor inhibitors. Finally, the hidden challenges with pharmacological therapy for HCC, feasible solutions for the future, and implications of possible presumptions to develop drugs for HCC treatment are reported.
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(This article belongs to the Special Issue Advances in the Treatment of Hepatocellular Carcinoma)
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Open AccessArticle
N-Benzylated 5-Hydroxybenzothiophene-2-carboxamides as Multi-Targeted Clk/Dyrk Inhibitors and Potential Anticancer Agents
by
Noha Mostafa, Po-Jen Chen, Sarah S. Darwish, Yu-Chieh Su, Ming-Hua Shiao, Gary A. Piazza, Ashraf H. Abadi, Matthias Engel and Mohammad Abdel-Halim
Cancers 2024, 16(11), 2033; https://doi.org/10.3390/cancers16112033 - 27 May 2024
Abstract
Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective
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Numerous studies have reported that Dyrk1A, Dyrk1B, and Clk1 are overexpressed in multiple cancers, suggesting a role in malignant disease. Here, we introduce a novel class of group-selective kinase inhibitors targeting Dyrk1A, Dyrk1B, and Clk1. This was achieved by modifying our earlier selective Clk1 inhibitors, which were based on the 5-methoxybenzothiophene-2-carboxamide scaffold. By incorporating a 5-hydroxy group, we increased the potential for additional hydrogen bond interactions that broadened the inhibitory effect to include Dyrk1A and Dyrk1B kinases. Within this series, compounds 12 and 17 emerged as the most potent multi-kinase inhibitors against Dyrk1A, Dyrk1B, and Clk1. Furthermore, when assessed against the most closely related kinases also implicated in cancer, the frontrunner compounds revealed additional inhibitory activity against Haspin and Clk2. Compounds 12 and 17 displayed high potency across various cancer cell lines with minimal effect on non-tumor cells. By examining the effect of these inhibitors on cell cycle distribution, compound 17 retained cells in the G2/M phase and induced apoptosis. Compounds 12 and 17 could also increase levels of cleaved caspase-3 and Bax, while decreasing the expression of the antiapoptotic Bcl-2 protein. These findings support the further study and development of these compounds as novel anticancer therapeutics.
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(This article belongs to the Special Issue Cancer Drug Discovery and Development)
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Open AccessArticle
Prognostic Impact of TERT Promoter Mutations in Adult-Type Diffuse Gliomas Based on WHO2021 Criteria
by
Yujin Lee, Chul-Kee Park and Sung-Hye Park
Cancers 2024, 16(11), 2032; https://doi.org/10.3390/cancers16112032 - 27 May 2024
Abstract
Mutation in the telomerase reverse transcriptase promoter (TERTp )is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this
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Mutation in the telomerase reverse transcriptase promoter (TERTp )is commonly observed in various malignancies, such as central nervous system (CNS) tumors, malignant melanoma, bladder cancer, and thyroid carcinoma. These mutations are recognized as significant poor prognostic factors for these tumors. In this investigation, a total of 528 cases of adult-type diffuse gliomas diagnosed at a single institution were reclassified according to the 2021 WHO classifications of CNS tumors, 5th edition (WHO2021). The study analyzed clinicopathological and genetic features, including TERTp mutations in each tumor. The impact of known prognostic factors on patient outcomes was analyzed through Kaplan–Meier survival and Cox regression analysis. TERTp mutations were predominantly identified in 94.1% of oligodendrogliomas (ODG), followed by 66.3% in glioblastoma, IDH-wildtype (GBM-IDHwt), and 9.2% of astrocytomas, IDH-mutant (A-IDHm). When considering A-IDHm and GBM as astrocytic tumors (Group 1) and ODGs (Group 2), TERTp mutations emerged as a significant adverse prognostic factor (p = 0.013) in Group 1. However, within each GBM-IDHwt and A-IDHm, the presence of TERTp mutations did not significantly impact patient prognosis (p = 0.215 and 0.268, respectively). Due to the high frequency of TERTp mutations in Group 2 (ODG) and their consistent prolonged survival, a statistical analysis to evaluate their impact on overall survival was deemed impractical. When considering MGMTp status, the combined TERTp-mutated and MGMTp-unmethylated group exhibited the worst prognosis in OS (p = 0.018) and PFS (p = 0.034) of GBM. This study confirmed that the classification of tumors according to the WHO2021 criteria effectively reflected prognosis. Both uni- and multivariate analyses in GBM, age, MGMTp methylation, and CDKN2A/B homozygous deletion were statistically significant prognostic factors while in univariate analysis in A-IDHm, grade 4, the Ki-67 index and MYCN amplifications were statistically significant prognostic factors. This study suggests that it is important to classify and manage tumors based on their genetic characteristics in adult-type diffuse gliomas.
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(This article belongs to the Special Issue Molecular Pathology of Brain Tumors)
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Influence of Aldehyde Dehydrogenase Inhibition on Stemness of Endometrial Cancer Stem Cells
by
Beatriz Serambeque, Catarina Mestre, Gabriela Correia-Barros, Ricardo Teixo, Carlos Miguel Marto, Ana Cristina Gonçalves, Francisco Caramelo, Isabel Silva, Artur Paiva, Hans C. Beck, Ana Sofia Carvalho, Maria Filomena Botelho, Maria João Carvalho, Rune Matthiesen and Mafalda Laranjo
Cancers 2024, 16(11), 2031; https://doi.org/10.3390/cancers16112031 - 27 May 2024
Abstract
Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role
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Endometrial cancer is one of the most common gynaecological malignancies. Although often diagnosed at an early stage, there is a subset of patients with recurrent and metastatic disease for whom current treatments are not effective. Cancer stem cells (CSCs) play a pivotal role in triggering tumorigenesis, disease progression, recurrence, and metastasis, as high aldehyde dehydrogenase (ALDH) activity is associated with invasiveness and chemotherapy resistance. Therefore, this study aimed to evaluate the effects of ALDH inhibition in endometrial CSCs. ECC-1 and RL95-2 cells were submitted to a sphere-forming protocol to obtain endometrial CSCs. ALDH inhibition was evaluated through ALDH activity and expression, sphere-forming capacity, self-renewal, projection area, and CD133, CD44, CD24, and P53 expression. A mass spectrometry-based proteomic study was performed to determine the proteomic profile of endometrial cancer cells upon N,N-diethylaminobenzaldehyde (DEAB). DEAB reduced ALDH activity and expression, along with a significant decrease in sphere-forming capacity and projection area, with increased CD133 expression. Additionally, DEAB modulated P53 expression. Endometrial cancer cells display a distinct proteomic profile upon DEAB, sharing 75 up-regulated and 30 down-regulated proteins. In conclusion, DEAB inhibits ALDH activity and expression, influencing endometrial CSC phenotype. Furthermore, ALDH18A1, SdhA, and UBAP2L should be explored as novel molecular targets for endometrial cancer.
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(This article belongs to the Special Issue Insights into Cancer Stem Cells)
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Nanomaterial-Driven Precision Immunomodulation: A New Paradigm in Therapeutic Interventions
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Alaa A. A. Aljabali, Mohammad A. Obeid, Omar Gammoh, Mohamed El-Tanani, Vijay Mishra, Yachana Mishra, Sumedha Kapre, Sushesh Srivatsa Palakurthi, Sk. Sarif Hassan, Debaleena Nawn, Kenneth Lundstrom, Altijana Hromić-Jahjefendić, Ángel Serrano-Aroca, Elrashdy M. Redwan, Vladimir N. Uversky and Murtaza M. Tambuwala
Cancers 2024, 16(11), 2030; https://doi.org/10.3390/cancers16112030 - 27 May 2024
Abstract
Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including
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Immunotherapy is a rapidly advancing field of research in the treatment of conditions such as cancer and autoimmunity. Nanomaterials can be designed for immune system manipulation, with precise targeted delivery and improved immunomodulatory efficacy. Here, we elaborate on various strategies using nanomaterials, including liposomes, polymers, and inorganic NPs, and discuss their detailed design intricacies, mechanisms, and applications, including the current regulatory issues. This type of nanomaterial design for targeting specific immune cells or tissues and controlling release kinetics could push current technological frontiers and provide new and innovative solutions for immune-related disorders and diseases without off-target effects. These materials enable targeted interactions with immune cells, thereby enhancing the effectiveness of checkpoint inhibitors, cancer vaccines, and adoptive cell therapies. Moreover, they allow for fine-tuning of immune responses while minimizing side effects. At the intersection of nanotechnology and immunology, nanomaterial-based platforms have immense potential to revolutionize patient-centered immunotherapy and reshape disease management. By prioritizing safety, customization, and compliance with regulatory standards, these systems can make significant contributions to precision medicine, thereby significantly impacting the healthcare landscape.
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(This article belongs to the Section Cancer Immunology and Immunotherapy)
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