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 18.2 days after submission; acceptance to publication is undertaken in 2.6 days (median values for papers published in this journal in the first 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
Therapeutic Targeting of Glioblastoma and the Interactions with Its Microenvironment
Cancers 2023, 15(24), 5790; https://doi.org/10.3390/cancers15245790 (registering DOI) - 10 Dec 2023
Abstract
Glioblastoma (GBM) is the most common primary malignant brain tumour, and it confers a dismal prognosis despite intensive multimodal treatments. Whilst historically, research has focussed on the evolution of GBM tumour cells themselves, there is growing recognition of the importance of studying the
[...] Read more.
Glioblastoma (GBM) is the most common primary malignant brain tumour, and it confers a dismal prognosis despite intensive multimodal treatments. Whilst historically, research has focussed on the evolution of GBM tumour cells themselves, there is growing recognition of the importance of studying the tumour microenvironment (TME). Improved characterisation of the interaction between GBM cells and the TME has led to a better understanding of therapeutic resistance and the identification of potential targets to block these escape mechanisms. This review describes the network of cells within the TME and proposes treatment strategies for simultaneously targeting GBM cells, the surrounding immune cells, and the crosstalk between them.
Full article
(This article belongs to the Special Issue Brain Tumor Microenvironment)
►
Show Figures
Open AccessArticle
AI-Based Risk Score from Tumour-Infiltrating Lymphocyte Predicts Locoregional-Free Survival in Nasopharyngeal Carcinoma
by
, , , , , , , and
Cancers 2023, 15(24), 5789; https://doi.org/10.3390/cancers15245789 (registering DOI) - 10 Dec 2023
Abstract
Background: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein–Barr virus DNA, are not sensitive to locoregional recurrence. Methods: We gathered 385 whole-slide
[...] Read more.
Background: Locoregional recurrence of nasopharyngeal carcinoma (NPC) occurs in 10% to 50% of cases following primary treatment. However, the current main prognostic markers for NPC, both stage and plasma Epstein–Barr virus DNA, are not sensitive to locoregional recurrence. Methods: We gathered 385 whole-slide images (WSIs) from haematoxylin and eosin (H&E)-stained NPC sections (n = 367 cases), which were collected from Sun Yat-sen University Cancer Centre. We developed a deep learning algorithm to detect tumour nuclei and lymphocyte nuclei in WSIs, followed by density-based clustering to quantify the tumour-infiltrating lymphocytes (TILs) into 12 scores. The Random Survival Forest model was then trained on the TILs to generate risk score. Results: Based on Kaplan–Meier analysis, the proposed methods were able to stratify low- and high-risk NPC cases in a validation set of locoregional recurrence with a statically significant result (p < 0.001). This finding was also found in distant metastasis-free survival (p < 0.001), progression-free survival (p < 0.001), and regional recurrence-free survival (p < 0.05). Furthermore, in both univariate analysis (HR: 1.58, CI: 1.13–2.19, p < 0.05) and multivariate analysis (HR:1.59, CI: 1.11–2.28, p < 0.05), we also found that our methods demonstrated a strong prognostic value for locoregional recurrence. Conclusion: The proposed novel digital markers could potentially be utilised to assist treatment decisions in cases of NPC.
Full article
(This article belongs to the Special Issue New Therapies and Immunological Findings in Nasopharyngeal Carcinoma)
►▼
Show Figures

Figure 1
Open AccessReview
Susceptibility Genes Associated with Multiple Primary Cancers
Cancers 2023, 15(24), 5788; https://doi.org/10.3390/cancers15245788 (registering DOI) - 10 Dec 2023
Abstract
With advancements in treatment and screening techniques, we have been witnessing an era where more cancer survivors harbor multiple primary cancers (MPCs), affecting approximately one in six patients. Identifying MPCs is crucial for tumor staging and subsequent treatment choices. However, the current clinicopathological
[...] Read more.
With advancements in treatment and screening techniques, we have been witnessing an era where more cancer survivors harbor multiple primary cancers (MPCs), affecting approximately one in six patients. Identifying MPCs is crucial for tumor staging and subsequent treatment choices. However, the current clinicopathological criteria for clinical application are limited and insufficient, making it challenging to differentiate them from recurrences or metastases. The emergence of next-generation sequencing (NGS) technology has provided a genetic perspective for defining multiple primary cancers. Researchers have found that, when considering multiple tumor pairs, it is crucial not only to examine well-known essential mutations like MLH1/MSH2, EGFR, PTEN, BRCA1/2, CHEK2, and TP53 mutations but also to explore certain pleiotropic loci. Moreover, specific deleterious mutations may serve as regulatory factors in second cancer development following treatment. This review aims to discuss these susceptibility genes and provide an explanation of their functions based on the signaling pathway background. Additionally, the association network between genetic signatures and different tumor pairs will be summarized.
Full article
(This article belongs to the Section Cancer Causes, Screening and Diagnosis)
Open AccessReview
Current State-of-the-Art Therapy for Malignant Pleural Mesothelioma and Future Options Centered on Immunotherapy
by
, , , , , , , , and
Cancers 2023, 15(24), 5787; https://doi.org/10.3390/cancers15245787 (registering DOI) - 10 Dec 2023
Abstract
Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two
[...] Read more.
Malignant pleural mesothelioma (MPM) is a locally aggressive disease related to asbestos exposure with a median survival for untreated patients of 4–8 months. The combination of chemotherapy based on platinum and antifolate is the standard treatment, and the addition of bevacizumab adds two months to median survival. Recently, in first-line treatment, immunotherapy combining nivolumab with ipilimumab has been shown to be superior to chemotherapy in the CheckMate-743 study in terms of overall survival (18.1 months), leading to its approval by the FDA and EMA. The positive results of this study represent a new standard of treatment for patients with MPM; however, not all patients will benefit from immunotherapy treatment. In an effort to improve the selection of patient candidates for immunotherapy for different tumors, biomarkers that have been associated with a greater possibility of response to treatment have been described. MPM is a type of tumor with low mutational load and neo-antigens, making it a relatively non-immunogenic tumor for T cells and possibly less susceptible to responding to immunotherapy. Different retrospective studies have shown that PD-L1 expression occurs in 20–40% of patients and is associated with a poor prognosis; however, the predictive value of PD-L1 in response to immunotherapy has not been confirmed. The purpose of this work is to review the state of the art of MPM treatment in the year 2023, focusing on the efficacy results of first-line or subsequent immunotherapy studies on patients with MPM and possible chemo-immunotherapy combination strategies. Additionally, potential biomarkers of response to immunotherapy will be reviewed, such as histology, PD-L1, lymphocyte populations, and TMB.
Full article
(This article belongs to the Section Cancer Immunology and Immunotherapy)
►▼
Show Figures

Figure 1
Open AccessReview
Life-Threatening Endocrinological Immune-Related Adverse Events of Immune Checkpoint Inhibitor Therapy
Cancers 2023, 15(24), 5786; https://doi.org/10.3390/cancers15245786 (registering DOI) - 10 Dec 2023
Abstract
Malignant neoplasms are currently one of the leading causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in research in cancer biology and immunity have led to the development of immunotherapy, which is now used on an
[...] Read more.
Malignant neoplasms are currently one of the leading causes of morbidity and mortality worldwide, posing a major public health challenge. However, recent advances in research in cancer biology and immunity have led to the development of immunotherapy, which is now used on an everyday basis in cancer treatment in addition to surgical treatment, classical cytostatics, and radiotherapy. The efficacy of immunotherapy has promoted the great popularity of this treatment among patients, as well as significant research interest. The increasing number of patients being treated with immunotherapy not only reassures physicians of the efficacy of this technique but also shows the wide spectrum of side effects of this therapy, which has not been considered before. Immune-related adverse events may affect many systems and organs, such as digestive, cardiovascular, respiratory, skin, or endocrine organs. Most complications have a mild or moderate course, but there are life-threatening manifestations that are essential to be aware of because if they are not properly diagnosed and treated on time, they can have fatal consequences. The purpose of this paper was to present the results of a literature review on the current state of knowledge on life-threatening endocrine side effects (such as adrenal crisis, thyroid storm, myxoedema crisis, diabetic ketoacidosis, and severe hypocalcaemia) of immune checkpoint inhibitors to provide information on symptoms, diagnostics, and management strategies.
Full article
(This article belongs to the Special Issue Immune Checkpoint Therapy and Biomarker in Cancer)
►▼
Show Figures

Graphical abstract
Open AccessArticle
One-Year Follow-Up after Multimodal Prehabilitation Interventions in Radical Cystectomy
Cancers 2023, 15(24), 5785; https://doi.org/10.3390/cancers15245785 (registering DOI) - 10 Dec 2023
Abstract
Multimodal prehabilitation is the process of enhancing physiological, nutritional, and psychological resilience to increase patients’ functional capacity before major cancer surgery and aims to empower the patient to withstand the pending stress of major surgery and ultimately to improve long-term outcomes. The effect
[...] Read more.
Multimodal prehabilitation is the process of enhancing physiological, nutritional, and psychological resilience to increase patients’ functional capacity before major cancer surgery and aims to empower the patient to withstand the pending stress of major surgery and ultimately to improve long-term outcomes. The effect of physical prehabilitation to counteract the physical decline in surgical cancer patients has been documented; however, long-term results have not yet been published. This follow-up study aims to evaluate 1-year results on the efficacy of physical prehabilitation after bladder cancer surgery. The efficacy of prehabilitation was measured over the course of 1 year in 107 patients randomized to (1) pre- and rehabilitation or (2) standard care divided by n = 50 in the intervention (I) and n = 57 in the standard group (S). Physical function was measured by muscle leg power, and nutritional status was expressed with handgrip strength. Prehabilitation in major bladder cancer surgery can significantly improve physical function with 19.8 Watt/kg (p = 0.04), lean body mass (p = 0.047) and body cell mass (p = 0.03), and regained nutritional status one year after surgery. The results demonstrate that the restoration of physical function is vital to a full recovery.
Full article
(This article belongs to the Special Issue Cystectomy for Bladder Cancer)
►▼
Show Figures

Figure 1
Open AccessReview
The Role of γδ T-Lymphocytes in Glioblastoma: Current Trends and Future Directions
by
, , , , , , and
Cancers 2023, 15(24), 5784; https://doi.org/10.3390/cancers15245784 (registering DOI) - 10 Dec 2023
Abstract
Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review
[...] Read more.
Cell-based immunotherapy for glioblastoma (GBM) encounters major challenges due to the infiltration-resistant and immunosuppressive tumor microenvironment (TME). γδ T cells, unconventional T cells expressing the characteristic γδ T cell receptor, have demonstrated promise in overcoming these challenges, suggesting great immunotherapeutic potential. This review presents the role of γδ T cells in GBM and proposes several research avenues for future studies. Using the PubMed, ScienceDirect, and JSTOR databases, we performed a review of the literature studying the biology of γδ T cells and their role in GBM treatment. We identified 15 studies focused on γδ T cells in human GBM. Infiltrative γδ T cells can incite antitumor immune responses in certain TMEs, though rapid tumor progression and TME hypoxia may impact the extent of tumor suppression. In the studies, available findings have shown both the potential for robust antitumor activity and the risk of protumor activity. While γδ T cells have potential as a therapeutic agent against GBM, the technical challenges of extracting, isolating, and expanding γδ T cells, and the activation of antitumoral versus protumoral cascades, remain barriers to their application. Overcoming these limitations may transform γδ T cells into a promising immunotherapy in GBM.
Full article
(This article belongs to the Special Issue The Role of Immunity in the Tumor Microenvironment)
►▼
Show Figures

Figure 1
Open AccessReview
How to Manage Philadelphia-Positive Acute Lymphoblastic Leukemia in Resource-Constrained Settings
by
and
Cancers 2023, 15(24), 5783; https://doi.org/10.3390/cancers15245783 (registering DOI) - 10 Dec 2023
Abstract
Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment
[...] Read more.
Recent studies have indicated that more than half of adult patients newly diagnosed with Ph+ ALL can now achieve a cure. However, determining the most suitable protocol for less-resourced settings can be challenging. In these situations, we must consider the potential for treatment toxicity and limited access to newer agents and alloSCT facilities. Currently, it is advisable to use less intensive induction regimens for Ph+ ALL. These regimens can achieve high rates of complete remission while causing fewer induction deaths. For consolidation therapy, chemotherapy should remain relatively intensive, with careful monitoring of the BCR-ABL1 molecular transcript and minimal residual disease. AlloSCT may be considered, especially for patients who do not achieve complete molecular remission or have high-risk genetic abnormalities, such as IKZF1-plus. If there is a loss of molecular response, it is essential to screen patients for ABL mutations and, ideally, change the TKI therapy. The T315I mutation is the most common mechanism for disease resistance, being targetable to ponatinib. Blinatumomab, a bispecific antibody, has shown significant synergy with TKIs in treating this disease. It serves as an excellent salvage therapy, aside from achieving outstanding results when incorporated into the frontline.
Full article
(This article belongs to the Section Cancer Epidemiology and Prevention)
►▼
Show Figures

Figure 1
Open AccessReview
Radiotherapy of Orbital and Ocular Adnexa Lymphoma: Literature Review and University of Catania Experience
by
, , , , , , , , , , , , , , , , and
Cancers 2023, 15(24), 5782; https://doi.org/10.3390/cancers15245782 (registering DOI) - 10 Dec 2023
Abstract
Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients
[...] Read more.
Orbital and ocular adnexa lymphomas are rare neoplasms confined to the orbital region. The prognosis is generally favorable, with a high proportion of localized disease, indolent clinical course, prolonged disease-free intervals, and low lymphoma-related mortality rate. We report our experience on eleven patients with confirmed histological diagnosis of lymphoma stage IE-IIE, treated between 2010 and 2021 with radiotherapy alone or in association with chemotherapy or immunotherapy. Eight patients were treated with primary radiotherapy only, while three received previous systemic treatments. Six patients were treated with Proton beam therapy (PBT), and five with external beam radiotherapy (EBRT). The five-year local control rate was 98%; only one patient developed an out-of-field recurrence. We also conducted a comprehensive literature review using electronic databases (PubMed, EMBASE, and Cochrane Library). Articles were selected based on their pertinence to treatment of the ocular and adnexal lymphoma focusing on radiotherapy techniques (electron beam radiotherapy, photon beam radiotherapy, or proton beam radiotherapy), treatment total dose, fractionation schedule, early and late radio-induced toxicities, and patient’s clinical outcome. Radiotherapy is an effective treatment option for orbital lymphoma, especially as standard treatment in the early stage of orbital lymphoma, with excellent local control rate and low rates of toxicity.
Full article
(This article belongs to the Special Issue Novel Insights in Ocular and Orbital Oncology: From Molecular Biology to Treatment Strategies)
►▼
Show Figures

Figure 1
Open AccessArticle
LincRNA01703 Facilitates CD81+ Exosome Secretion to Inhibit Lung Adenocarcinoma Metastasis via the Rab27a/SYTL1/CD81 Complex
by
, , , , , , , , , , , , and
Cancers 2023, 15(24), 5781; https://doi.org/10.3390/cancers15245781 (registering DOI) - 09 Dec 2023
Abstract
Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the
[...] Read more.
Metastasis, a major cause of cancer-related mortality worldwide, frequently occurs early in the diagnosis of lung adenocarcinoma (LUAD). However, the precise molecular mechanisms governing the aggressive metastatic behavior of LUAD remain incompletely understood. In this study, we present compelling evidence indicating that the long noncoding RNA linc01703 is significantly downregulated in metastatic lung cancer cells. Intriguingly, in vivo experiments revealed that Linc01703 exerted a profound inhibitory effect on lung cancer metastasis without discernible impact on the in vitro proliferation or invasion capacities of LUAD cells. Mechanistically, Linc01703 enhanced the interaction between Rab27a, SYTL1, and CD81, consequently promoting the secretion of CD81+ exosomes. These exosomes, in turn, suppressed the infiltration of immune cells within the tumor microenvironment, thereby impeding LUAD metastasis. Importantly, our analysis of lung cancer tissues revealed a correlation between reduced CD81 expression and an unfavorable patient prognosis. Collectively, our findings suggest that Linc01703 functions as a metastasis suppressor by facilitating the secretion of CD81+ exosomes through the formation of the Rab27a/SYTL1/CD81 complex.
Full article
(This article belongs to the Special Issue Exosomes in Cancer Metastasis)
►▼
Show Figures

Figure 1
Open AccessArticle
Prognostic Factors of Platinum-Refractory Advanced Urothelial Carcinoma Treated with Pembrolizumab
by
, , , , , , , , and
Cancers 2023, 15(24), 5780; https://doi.org/10.3390/cancers15245780 (registering DOI) - 09 Dec 2023
Abstract
Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for
[...] Read more.
Introduction: Immune checkpoint inhibitor (ICI) therapy has significantly improved the prognosis of some patients with advanced urothelial carcinoma (UC), but it does not provide high therapeutic efficacy in all patients. Therefore, identifying predictive biomarkers is crucial in determining which patients are candidates for ICI treatment. This study aimed to identify the predictors of ICI treatment response in patients with platinum-refractory advanced UC treated with pembrolizumab. Methods: Patients with platinum-refractory advanced UC who had received pembrolizumab at two hospitals in Japan were included. Univariate and multivariate analyses were performed to identify biomarkers for progression-free survival (PFS) and overall survival (OS). Results: Forty-one patients were evaluable for this analysis. Their median age was 75 years, and the vast majority of the patients were male (85.4%). The objective response rate was 29.3%, with a median overall survival (OS) of 17.8 months. On multivariate analysis, an Eastern Cooperative Oncology Group performance status (ECOG-PS) ≥ 2 (HR = 6.33, p = 0.03) and a baseline neutrophil-to-lymphocyte ratio (NLR) > 3 (HR = 2.79, p = 0.04) were significantly associated with poor OS. Antibiotic exposure did not have a significant impact on either PFS or OS. Conclusions: ECOG-PS ≥ 2 and baseline NLR > 3 were independent risk factors for OS in patients with platinum-refractory advanced UC treated with pembrolizumab. Antibiotic exposure was not a predictor of ICI treatment response.
Full article
(This article belongs to the Collection Urological Cancer)
►▼
Show Figures

Figure 1
Open AccessReview
In Vitro Three-Dimensional (3D) Models for Melanoma Immunotherapy
by
, , , , , , and
Cancers 2023, 15(24), 5779; https://doi.org/10.3390/cancers15245779 (registering DOI) - 09 Dec 2023
Abstract
Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may
[...] Read more.
Melanoma is responsible for the majority of skin cancer-related fatalities. Immune checkpoint inhibitor (ICI) treatments have revolutionized the management of the disease by significantly increasing patient survival rates. However, a considerable number of tumors treated with these drugs fail to respond or may develop resistance over time. Tumor growth and its response to therapies are critically influenced by the tumor microenvironment (TME); it directly supports cancer cell growth and influences the behavior of surrounding immune cells, which can become tumor-permissive, thereby rendering immunotherapies ineffective. Ex vivo modeling of melanomas and their response to treatment could significantly advance our understanding and predictions of therapy outcomes. Efforts have been directed toward developing reliable models that accurately mimic melanoma in its appropriate tissue environment, including tumor organoids, bioprinted tissue constructs, and microfluidic devices. However, incorporating and modeling the melanoma TME and immune component remains a significant challenge. Here, we review recent literature regarding the generation of in vitro 3D models of normal skin and melanoma and the approaches used to incorporate the immune compartment in such models. We discuss how these constructs could be combined and used to test immunotherapies and elucidate treatment resistance mechanisms. The development of 3D in vitro melanoma models that faithfully replicate the complexity of the TME and its interaction with the immune system will provide us with the technical tools to better understand ICI resistance and increase its efficacy, thereby improving personalized melanoma therapy.
Full article
(This article belongs to the Special Issue Tumor Microenvironment and Melanoma Therapy)
►▼
Show Figures

Graphical abstract
Open AccessArticle
Plasma Assay of Cell-Free Methylated DNA Markers of Colorectal Cancer: A Tumor-Agnostic Approach to Monitor Recurrence and Response to Anticancer Therapies
by
, , , , , , , , , , , , and
Cancers 2023, 15(24), 5778; https://doi.org/10.3390/cancers15245778 (registering DOI) - 09 Dec 2023
Abstract
Background: Radiographic surveillance of colorectal cancer (CRC) after curative-intent therapy is costly and unreliable. Methylated DNA markers (MDMs) detected primary CRC and metastatic recurrence with high sensitivity and specificity in cross-sectional studies. This study evaluated using serial MDMs to detect recurrence and monitor
[...] Read more.
Background: Radiographic surveillance of colorectal cancer (CRC) after curative-intent therapy is costly and unreliable. Methylated DNA markers (MDMs) detected primary CRC and metastatic recurrence with high sensitivity and specificity in cross-sectional studies. This study evaluated using serial MDMs to detect recurrence and monitor the treatment response to anti-cancer therapies. Methods: A nested case-control study was drawn from a prospective cohort of patients with CRC who completed curative-intent therapy for CRC of all stages. Plasma MDMs were assayed vis target enrichment long-probe quantitative-amplified signal assays, normalized to B3GALT6, and analyzed in combination with serum carcinoembryonic antigen to yield an MDM score. Clinical information, including treatment and radiographic measurements of the tumor burden, were longitudinally collected. Results: Of the 35 patients, 18 had recurrence and 17 had no evidence of disease during the study period. The MDM score was positive in 16 out of 18 patients who recurred and only 2 of the 17 patients without recurrence. The MDM score detected recurrence in 12 patients preceding clinical or radiographic detection of recurrent CRC by a median of 106 days (range 90–232 days). Conclusions: Plasma MDMs can detect recurrent CRC prior to radiographic detection; this tumor-agnostic liquid biopsy approach may assist cancer surveillance and monitoring.
Full article
(This article belongs to the Special Issue Liquid Biopsy in Cancer 2.0)
►▼
Show Figures

Figure 1
Open AccessArticle
Association of MGMT Promoter and Enhancer Methylation with Genetic Variants, Clinical Parameters, and Demographic Characteristics in Glioblastoma
by
, , , , , and
Daniel Berger
Cancers 2023, 15(24), 5777; https://doi.org/10.3390/cancers15245777 (registering DOI) - 09 Dec 2023
Abstract
The response of glioblastoma (GBM) patients to the alkylating agent temozolomide (TMZ) vitally depends on the expression level of the repair protein O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT is strongly regulated by promoter methylation, the methylation status of the MGMT promoter has emerged as
[...] Read more.
The response of glioblastoma (GBM) patients to the alkylating agent temozolomide (TMZ) vitally depends on the expression level of the repair protein O6-methylguanine-DNA methyltransferase (MGMT). Since MGMT is strongly regulated by promoter methylation, the methylation status of the MGMT promoter has emerged as a prognostic and predictive biomarker for GBM patients. By determining the methylation levels of the four enhancers located within or close to the MGMT gene, we recently found that enhancer methylation contributes to MGMT regulation. In this study, we investigated if methylation of the four enhancers is associated with SNP rs16906252, TERT promoter mutations C228T and C250T, TERT SNP rs2853669, proliferation index Ki-67, overall survival (OS), age, and sex of the patients. In general, associations with genetic variants, clinical parameters, and demographic characteristics were caused by a complex interplay of multiple CpGs in the MGMT promoter and of multiple CpGs in enhancer regions. The observed associations for intragenic enhancer 4, located in intron 2 of MGMT, differed from associations observed for the three intergenic enhancers. Some findings were restricted to subgroups of samples with either methylated or unmethylated MGMT promoters, underpinning the relevance of the MGMT promoter status in GBMs.
Full article
(This article belongs to the Special Issue Alterations in Cis-Regulatory Elements and Non-Coding RNAs in Human Cancer)
►▼
Show Figures

Figure 1
Open AccessArticle
Defining an Abnormal Geriatric Assessment: Which Deficits Matter Most?
Cancers 2023, 15(24), 5776; https://doi.org/10.3390/cancers15245776 (registering DOI) - 09 Dec 2023
Abstract
At present, there is no clear definition of what constitutes an abnormal geriatric assessment (GA) in geriatric oncology. Various threshold numbers of abnormal GA domains are often used, but how well these are associated with treatment plan modification (TPM) and whether specific GA
[...] Read more.
At present, there is no clear definition of what constitutes an abnormal geriatric assessment (GA) in geriatric oncology. Various threshold numbers of abnormal GA domains are often used, but how well these are associated with treatment plan modification (TPM) and whether specific GA domains are more important in this context remains uncertain. A retrospective review of the geriatric oncology clinic database at Princess Margaret Cancer Centre in Toronto, Canada, including new patients seen for treatment decision making from May 2015 to June 2022, was conducted. Logistic regression modelling was performed to determine the association between various predictor variables (including the GA domains and numerical thresholds) and TPM. The study cohort (n = 736) had a mean age of 80.7 years, 46.1% was female, and 78.3% had a VES-13 score indicating vulnerability (≥3). In the univariable analysis, the best-performing threshold number of abnormal domains based on area under the curve (AUC) was 4 (AUC 0.628). The best-performing multivariable model (AUC 0.704) included cognition, comorbidities, and falls risk. In comparison, the multivariable model with the sole addition of the threshold of 4 had an AUC of 0.689. Overall, an abnormal GA may be best defined as one with abnormalities in the domains of cognition, comorbidities, and falls risk. The optimal numerical threshold to predict TPM is 4.
Full article
(This article belongs to the Special Issue Current Challenges in Geriatric Oncology)
►▼
Show Figures

Figure 1
Open AccessArticle
Inhibition of Survivin Homodimerization Decreases Neuroblastoma Cell Growth
by
, , , , , , and
Cancers 2023, 15(24), 5775; https://doi.org/10.3390/cancers15245775 (registering DOI) - 09 Dec 2023
Abstract
Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are
[...] Read more.
Increased expression of BIRC5/survivin, a crucial regulator of the mitotic spindle checkpoint, is associated with poor prognosis in neuroblastoma (NB), the most common extracranial tumor of childhood. Transcriptional inhibitors of survivin have been tested in adult cancers and inhibitors of survivin homodimerization are emerging. We compared genetic inhibition of survivin transcription with the inhibition of survivin homodimerization by S12 and LQZ-7I, chosen from a larger panel of survivin dimerization inhibitors with activity against NB cells. Mice hemizygous for Birc5 were crossed with NB-prone TH-MYCN mice to generate Birc5+/-/MYCNtg/+ mice. The marked decrease of survivin transcription in these mice did not suffice to attenuate the aggressiveness of NB, even when tumors were transplanted into wild-type mice to assure that immune cell function was not compromised by the lack of survivin. In contrast, viability, clonogenicity and anchorage-independent growth of NB cells were markedly decreased by S12. S12 administered systemically to mice with subcutaneous NB xenotransplants decreased intratumoral hemorrhage, albeit not tumor growth. LQZ-7I, which directly targets the survivin dimerization interface, was efficacious in controlling NB cell growth in vitro at markedly lower concentrations compared to S12. LQZ-7I abrogated viability, clonogenicity and anchorage-independent growth, associated with massively distorted mitotic spindle formation. In vivo, LQZ-7I effectively reduced tumor size and cell proliferation of NB cells in CAM assays without apparent toxicity to the developing chick embryo. Collectively, these findings show that inhibiting survivin homodimerization with LQZ-7I holds promise for the treatment of NB and merits further investigation.
Full article
(This article belongs to the Section Pediatric Oncology)
►▼
Show Figures

Figure 1
Open AccessArticle
BR109, a Novel Fully Humanized T-Cell-Engaging Bispecific Antibody with GPRC5D Binding, Has Potent Antitumor Activities in Multiple Myeloma
by
, , , , , , , , , and
Cancers 2023, 15(24), 5774; https://doi.org/10.3390/cancers15245774 (registering DOI) - 09 Dec 2023
Abstract
At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to
[...] Read more.
At present, multiple myeloma (MM) is still an essentially incurable hematologic malignancy. Although BCMA-targeted therapies have achieved remarkable results, BCMA levels were found to be downregulated in patients with MM who relapsed after these treatments. Therefore, the search for other antigens specific to MM has become a priority. Independently of BCMA expression, G-protein-coupled receptor family C group 5 member D (GPRC5D) is mainly expressed in the plasma cells of MM patients, while it is expressed in a limited number of normal tissues. Combining MM-specific antigen GPRC5D and T-cell-mediated therapies would be a promising therapeutic strategy for MM. Recently, we constructed a new anti-GPRC5D × anti-CD3 T-cell-engaging bispecific antibody (TCB), BR109, which was capable of binding to human GPRC5D and human CD3ε. Moreover, BR109 was proven to have relatively good stability and antitumor activity. BR109 could specifically trigger T-cell-mediated cytotoxicity against many GPRC5D-positive MM cells in vitro. Meanwhile, antitumor activity was demonstrated in MM cell line xenograft mouse models with human immune cell reconstitution. These preclinical studies have formed a solid foundation for the evaluation of MM treatment efficacy in clinical trials.
Full article
(This article belongs to the Special Issue Multiple Myeloma—Biology, Diagnosis, Treatment and Prognosis)
►▼
Show Figures

Figure 1
Open AccessArticle
A Novel Metastatic Estrogen Receptor-Expressing Breast Cancer Model with Antiestrogen Responsiveness
by
, , , , , , , , , , , and
Cancers 2023, 15(24), 5773; https://doi.org/10.3390/cancers15245773 (registering DOI) - 09 Dec 2023
Abstract
Most women diagnosed with breast cancer (BC) have estrogen receptor alpha-positive (ER+) disease. The current mouse models of ER+ BC often rely on exogenous estrogen to encourage metastasis, which modifies the immune system and the function of some tissues like bone. Other studies
[...] Read more.
Most women diagnosed with breast cancer (BC) have estrogen receptor alpha-positive (ER+) disease. The current mouse models of ER+ BC often rely on exogenous estrogen to encourage metastasis, which modifies the immune system and the function of some tissues like bone. Other studies use genetically modified or immunocompromised mouse strains, which do not accurately replicate the clinical disease. To create a model of antiestrogen responsive BC with spontaneous metastasis, we developed a mouse model of 4T1.2 triple-negative (TN) breast cancer with virally transduced ER expression that metastasizes spontaneously without exogenous estrogen stimulation and is responsive to antiestrogen drugs. Our mouse model exhibited upregulated ER-responsive genes and multi-organ metastasis without exogenous estrogen administration. Additionally, we developed a second TN BC cell line, E0771/bone, to express ER, and while it expressed ER-responsive genes, it lacked spontaneous metastasis to clinically important tissues. Following antiestrogen treatment (tamoxifen, ICI 182,780, or vehicle control), 4T1.2- and E0771/bone-derived tumor volumes and weights were significantly decreased, exemplifying antiestrogen responsivity in both cell lines. This 4T1.2 tumor model, which expresses the estrogen receptor, metastasizes spontaneously, and responds to antiestrogen treatment, will allow for further investigation into the biology and potential treatment of metastasis.
Full article
(This article belongs to the Special Issue Bone and Spine Metastases)
►▼
Show Figures

Figure 1
Open AccessReview
Ampullary Adenocarcinoma: A Review of the Mutational Landscape and Implications for Treatment
Cancers 2023, 15(24), 5772; https://doi.org/10.3390/cancers15245772 (registering DOI) - 09 Dec 2023
Abstract
Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved
[...] Read more.
Ampullary carcinomas represent less than 1% of all gastrointestinal malignancies with an incidence of approximately 6 cases per 1 million. Histologic examination and immunohistochemistry have been traditionally used to categorize ampullary tumors into intestinal, pancreatobiliary or mixed subtypes. Intestinal-subtype tumors may exhibit improved survival versus the pancreatobiliary subtype, although studies on the prognostic value of immunomorphologic classification have been inconsistent. Genomic classifiers hold the promise of greater reliability, while providing potential targets for precision oncology. Multi-institutional collaboration will be necessary to better understand how molecular classification can guide type and sequencing of multimodality therapy.
Full article
(This article belongs to the Special Issue Surgical Management of Gastrointestinal Cancers)
Open AccessArticle
Impaired Expression of the Salvador Homolog-1 Gene Is Associated with the Development and Progression of Colorectal Cancer
by
, , , , , and
Cancers 2023, 15(24), 5771; https://doi.org/10.3390/cancers15245771 (registering DOI) - 08 Dec 2023
Abstract
Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study
[...] Read more.
Salvador homolog-1 (SAV1) is a component of the Hippo pathway that regulates tissue growth and homeostasis by affecting diverse cell processes, including apoptosis, cell division, and differentiation. The aberrant expression of Hippo pathway components has been observed in various human cancers. This study aimed to examine the expression level of the SAV1 gene in colorectal cancer (CRC) and its prognostic value and associations with tumor progression. We obtained matched pairs of tumor tissue and non-cancerous mucosa of the large intestine from 94 CRC patients as well as 40 colon biopsies of healthy subjects collected during screening colonoscopy. The tissue samples and CRC cell lines were quantified for SAV1 mRNA levels using the quantitative polymerase chain reaction method, while SAV1 protein expression was estimated in the paired tissues of CRC patients using immunohistochemistry. The average level of SAV1 mRNA was decreased in 93.6% of the tumor tissues compared to the corresponding non-cancerous tissues and biopsies of healthy colon mucosa. A downregulated expression of SAV1 mRNA was also noted in the CRC cell lines. Although the average SAV1 immunoreactivity was increased in the CRC samples compared to the non-cancerous tissues, a decreased immunoreactivity of the SAV1 protein in the tumor specimens was associated with lymph node involvement and higher TNM disease stage and histological grade. The results of our study suggest that the impaired expression of SAV1 is involved in CRC progression.
Full article
(This article belongs to the Special Issue Tumorigenesis Mechanism of Colorectal Cancer)

Journal Menu
► ▼ Journal Menu-
- Cancers Home
- Aims & Scope
- Editorial Board
- Reviewer Board
- Topical Advisory Panel
- Instructions for Authors
- Special Issues
- Topics
- Sections & Collections
- Article Processing Charge
- Indexing & Archiving
- Editor’s Choice Articles
- Most Cited & Viewed
- Journal Statistics
- Journal History
- Journal Awards
- Society Collaborations
- Conferences
- Editorial Office
Journal Browser
► ▼ Journal BrowserHighly Accessed Articles
Latest Books
E-Mail Alert
News
Topics
Topic in
Biology, Cancers, Current Oncology, Hematology Reports, Medical Sciences
Advances in Tumor Microenvironment
Topic Editors: Hongzhou Cai, Lixin Hua, Mantang Qiu, Wenzhi LiDeadline: 20 December 2023
Topic in
Biomedicines, Cancers, Diagnostics, JCM, Neurology International
Novel Diagnostic and Therapeutic Strategies in Gliomas
Topic Editors: Athanassios P. Kyritsis, George AlexiouDeadline: 31 December 2023
Topic in
Brain Sciences, Cancers, JCM, JVD, Neurology International
Inflammation in Neuro-Oncological Diseases and in Neuro-Vascular Diseases
Topic Editors: Erdem Güresir, Johannes Wach, Martin VychopenDeadline: 31 March 2024
Topic in
Biomedicines, BioMedInformatics, Cancers, JCM, Cells, Current Oncology
Cancer Immunity and Immunotherapy: Early Detection, Diagnosis, Systemic Treatments, Novel Biomarkers, and Resistance Mechanisms
Topic Editors: Tao Jiang, Yongchang ZhangDeadline: 20 April 2024

Conferences
Special Issues
Special Issue in
Cancers
Oxidative Stress and Cancer: Possible Beneficial and Antioxidant Strategies
Guest Editor: Rita RezzaniDeadline: 15 December 2023
Special Issue in
Cancers
Perihilar Cholangiocarcinoma
Guest Editors: Bas Groot Koerkamp, Stefan Büttner, Pim B. OlthofDeadline: 20 December 2023
Special Issue in
Cancers
Targeted Therapy for Bladder Cancer
Guest Editor: Maximilian BurgerDeadline: 31 December 2023
Special Issue in
Cancers
MRI Biomarkers of Cancer
Guest Editor: Alexey SurovDeadline: 5 January 2024
Topical Collections
Topical Collection in
Cancers
Drug Resistance and Novel Therapies in Cancers
Collection Editor: Zhixiang Wang