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Cancers
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“Cancer Metastasis” in 2023–2024
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“Cancer Metastasis” in 2023–2024

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

Deadline for manuscript submissions: 30 June 2025 | Viewed by 7237

Special Issue Editor

Prof. Dr. Lance Liotta

E-Mail Website
Guest Editor
Center for Applied Proteomics and Molecular Medicine, George Mason University, Manassas, VA, 20110, USA
Interests: diagnostics; cancer molecular therapeutics; microdissection (laser capture microdissection); proteomics (reverse phase protein microarrays); biomarker harvesting nanoparticles; preservation chemistries for molecular analysis

Special Issue Information

Dear Colleagues,

The topic of this Special Issue is cancer metastasis, the lethal aspect of malignant neoplasms. Recently, there has been a surge of discoveries addressing critical mechanistic questions about individual steps within the complicated process of metastasis. Nevertheless, there is much we do not know about this insidious property of cancer. For this issue, we broadly invite investigators to submit original research articles, or opinion pieces, on any aspect of metastasis biology or the clinical treatment of metastasis. Example topics include (but are not limited to) the following: (a) transition from pre malignant to invasive cancer, (b) molecular mechanisms of invasion and cancer cell plasticity, (c) immune cooperation/suppression of metastasis, (d) lymphatic versus hematogenous spread, tumor suppression of the draining lymph node, (e) extravasation and circulating tumor cells, (f) clonal evolution and stem-like cells in metastasis, (g) bone metastasis, (h) personalized treatment of metastasis, (i) dormancy of metastasis, (j) exosome biology and metastasis, (k) clinical detection of metastasis, and (l) immunotherapy of metastasis.

Prof. Dr. Lance Liotta
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • immunotherapy
  • tumor suppression
  • cancer metastasis

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Published Papers (6 papers)

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Research

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13 pages, 1184 KiB  
Article
Outcome and Survival Analysis of Multicenter Lung Metastasectomy for Primary Liver Tumor with Pulmonary Metastasis
by Yu-Cheng Chang, Xu-Heng Chiang, Yu-Ting Tseng, Shuenn-Wen Kuo, Pei-Ming Huang, Mong-Wei Lin, Hsao-Hsun Hsu and Jin-Shing Chen
Cancers 2024, 16(17), 3007; https://doi.org/10.3390/cancers16173007 - 29 Aug 2024
Viewed by 445
Abstract
Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary [...] Read more.
Oligopulmonary metastases from primary liver tumors are typically treated surgically. We evaluated the clinical outcomes after lung metastasectomy in patients with pulmonary metastases from primary liver tumors. We retrospectively enrolled 147 consecutive patients with lung metastases from liver cancer who had undergone pulmonary metastasectomies at three medical centers between February 2007 and December 2020. All patients were pathologically confirmed to have lung metastases from liver cancer. Among the 147 patients, 110, 17, and 20 initially underwent surgical resection, radiofrequency ablation, and transcatheter arterial embolization, respectively. The 5-year overall survival (OS) in the study cohort was 22%. Univariate analysis revealed four factors associated with better OS: surgical resection as the initial primary liver tumor treatment (p = 0.004), a disease-free interval exceeding 12 months after the initial liver surgery (p = 0.036), a lower Model for End-Stage Liver Disease (MELD)-Na score (≤20) for liver cirrhosis (p = 0.044), and the absence of local liver tumor recurrence at the time of pulmonary metastasectomy (p = 0.004). Multivariate analysis demonstrated that surgical resection as the initial primary liver tumor treatment and lower MELD-Na scores significantly correlated with better OS. Our findings can assist thoracic surgeons in selecting suitable patients for surgery and predicting surgical outcomes. Full article
(This article belongs to the Special Issue “Cancer Metastasis” in 2023–2024)
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11 pages, 960 KiB  
Article
Inverse Correlation between pks-Carrying Escherichia coli Abundance in Colorectal Cancer Liver Metastases and the Number of Organs Involved in Recurrence
by Yasuyuki Shigematsu, Rumiko Saito, Hiroaki Kanda, Yu Takahashi, Kengo Takeuchi, Shunji Takahashi and Kentaro Inamura
Cancers 2024, 16(17), 3003; https://doi.org/10.3390/cancers16173003 - 29 Aug 2024
Viewed by 514
Abstract
Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but [...] Read more.
Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of pks+ E. coli in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of pks+ E. coli in fresh-frozen specimens were quantified as “very low” (<50th percentile), “low” (50th to 75th percentiles), and “high” (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. pks+ E. coli was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of pks+E. coli were associated with decreased serum CRP levels and reduced densities of CD4+ cells and CD163+ cells in the tumor-immune microenvironment. The “high” pks+ E. coli group had fewer metastatic organs involved than the “very low” pks+ E. coli group (mean number of organs: 1.00 vs. 1.23). These findings suggest that pks+ E. coli play a modulating role in CRC metastasis. Full article
(This article belongs to the Special Issue “Cancer Metastasis” in 2023–2024)
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13 pages, 1250 KiB  
Article
Navigating Post-Operative Outcomes: A Comprehensive Reframing of an Original Graded Prognostic Assessment in Patients with Brain Metastases
by Maria Goldberg, Michel G. Mondragon-Soto, Laura Dieringer, Ghaith Altawalbeh, Paul Pöser, Lea Baumgart, Benedikt Wiestler, Jens Gempt, Bernhard Meyer and Amir Kaywan Aftahy
Cancers 2024, 16(2), 291; https://doi.org/10.3390/cancers16020291 - 10 Jan 2024
Cited by 1 | Viewed by 1637
Abstract
Background: Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. [...] Read more.
Background: Graded Prognostic Assessment (GPA) has been proposed for various brain metastases (BMs) tailored to the primary histology and molecular profiles. However, it does not consider whether patients have been operated on or not and does not include surgical outcomes as prognostic factors. The residual tumor burden (RTB) is a strong predictor of overall survival. We validated the GPA score and introduced “volumetric GPA” in the largest cohort of operated patients and further explored the role of RTB as an additional prognostic factor. Methods: A total of 630 patients with BMs between 2007 and 2020 were included. The four GPA components were analyzed. The validity of the original score was assessed using Cox regression, and a modified index incorporating RTB was developed by comparing the accuracy, sensitivity, specificity, F1-score, and AUC parameters. Results: GPA categories showed an association with survival: age (p < 0.001, hazard ratio (HR) 2.9, 95% confidence interval (CI) 2.5–3.3), Karnofsky performance status (KPS) (p < 0.001, HR 1.3, 95% CI 1.2–1.5), number of BMs (p = 0.019, HR 1.4, 95% CI 1.1–1.8), and the presence of extracranial manifestation (p < 0.001, HR 3, 95% CI 1.6–2.5). The median survival for GPA 0–1 was 4 months; for GPA 1.5–2, it was 12 months; for GPA 2.5–3, it was 21 months; and for GPA 3.5–4, it was 38 months (p < 0.001). RTB was identified as an independent prognostic factor. A cut-off of 2 cm3 was used for further analysis, which showed a median survival of 6 months (95% CI 4–8) vs. 13 months (95% CI 11–14, p < 0.001) for patients with RTB > 2 cm3 and <2 cm3, respectively. RTB was added as an additional component for a modified volumetric GPA score. The survival rates with the modified GPA score were: GPA 0–1: 4 months, GPA 1.5–2: 7 months, GPA 2.5–3: 18 months, and GPA 3.5–4: 34 months. Both scores showed good stratification, with the new score showed a trend towards better discrimination in patients with more favorable prognoses. Conclusion: The prognostic value of the original GPA was confirmed in our cohort of patients who underwent surgery for BM. The RTB was identified as a parameter of high prognostic significance and was incorporated into an updated “volumetric GPA”. This score provides a novel tool for prognosis and clinical decision making in patients undergoing surgery. This method may be useful for stratification and patient selection for further treatment and in future clinical trials. Full article
(This article belongs to the Special Issue “Cancer Metastasis” in 2023–2024)
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21 pages, 2454 KiB  
Article
Clinical Application of the Association between Genetic Alteration and Intraoperative Fluorescence Activity of 5-Aminolevulinic Acid during the Resection of Brain Metastasis of Lung Adenocarcinoma
by Hyeon Yeong Jeong, Won Jun Suh, Seung Hwan Kim, Taek Min Nam, Ji Hwan Jang, Kyu Hong Kim, Seok Hyun Kim and Young Zoon Kim
Cancers 2024, 16(1), 88; https://doi.org/10.3390/cancers16010088 - 23 Dec 2023
Viewed by 879
Abstract
The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection [...] Read more.
The primary objective of this study was to investigate the association of certain genetic alterations and intraoperative fluorescent activity of 5-aminolevulinic acid (ALA) in brain metastasis (BM) of lung adenocarcinoma. A retrospective cohort study was conducted among 72 patients who underwent surgical resection of BM of lung adenocarcinoma at our institute for five years. Cancer cell infiltration was estimated by the intraoperative fluorescent activity of 5-ALA, and genetic alterations were analyzed by next-generation sequencing (NGS). The sensitivity and specificity for detecting cancer cell infiltration using 5-ALA were 87.5% and 96.4%, respectively. Genes associated with cell cycle regulation (p = 0.003) and cell proliferation (p = 0.044) were significantly associated with positive fluorescence activity of 5-ALA in the adjacent brain tissue. Genetic alterations in cell cycle regulation and cell proliferation were also associated with shorter recurrence-free survival (p = 0.013 and p = 0.042, respectively) and overall survival (p = 0.026 and p = 0.042, respectively) in the multivariate analysis. The results suggest that genetic alterations in cell cycle regulation and cell proliferation are associated with positive fluorescence activity of 5-ALA in the adjacent infiltrative brain tissue and influence the clinical outcome of BM of lung adenocarcinoma. Full article
(This article belongs to the Special Issue “Cancer Metastasis” in 2023–2024)
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Review

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11 pages, 651 KiB  
Review
Treatment Strategies for Locoregional Recurrence in Esophageal Squamous-Cell Carcinoma: An Updated Review
by Atsushi Mitamura, Shingo Tsujinaka, Toru Nakano, Kentaro Sawada and Chikashi Shibata
Cancers 2024, 16(14), 2539; https://doi.org/10.3390/cancers16142539 - 14 Jul 2024
Viewed by 1247
Abstract
Emerging evidence has shown remarkable advances in the multimodal treatment of esophageal squamous-cell carcinoma. Despite these advances, the oncological outcomes for advanced esophageal cancer remain controversial due to the frequent observation of local recurrence in the regional or other lymph nodes and distant [...] Read more.
Emerging evidence has shown remarkable advances in the multimodal treatment of esophageal squamous-cell carcinoma. Despite these advances, the oncological outcomes for advanced esophageal cancer remain controversial due to the frequent observation of local recurrence in the regional or other lymph nodes and distant metastasis after curative treatment. For cases of locoregional recurrence in the cervical lymph nodes alone, salvage surgery with lymph node dissection generally provides a good prognosis. However, if recurrence occurs in multiple regions, the oncological efficacy of surgery may be limited. Radiotherapy/chemoradiotherapy can be employed for unresectable or recurrent cases, as well as for selected cases in neo- or adjuvant settings. Dose escalation and toxicity are potential issues with conventional three-dimensional conformal radiotherapy; however, more precise therapeutic efficacy can be obtained using technical modifications with improved targeting and conformality, or with the use of proton beam therapy. The introduction of immune checkpoint inhibitors, including pembrolizumab or nivolumab, in addition to chemotherapy, has been shown to improve the overall survival in unresectable, advanced/recurrent cases. For patients with lymph node recurrence in multiple regions, chemotherapy (5-fluorouracil [5-FU] plus cisplatin) and combination therapy with nivolumab and ipilimumab have shown comparable oncological efficacy. Further prospective studies are needed to improve the treatment outcomes in patients with esophageal cancer with locoregional recurrence. Full article
(This article belongs to the Special Issue “Cancer Metastasis” in 2023–2024)
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Other

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14 pages, 1136 KiB  
Systematic Review
A Systematic Review on Artificial Intelligence Evaluating Metastatic Prostatic Cancer and Lymph Nodes on PSMA PET Scans
by Jianliang Liu, Thomas P. Cundy, Dixon T. S. Woon and Nathan Lawrentschuk
Cancers 2024, 16(3), 486; https://doi.org/10.3390/cancers16030486 - 23 Jan 2024
Cited by 2 | Viewed by 1779
Abstract
Early detection of metastatic prostate cancer (mPCa) is crucial. Whilst the prostate-specific membrane antigen (PSMA) PET scan has high diagnostic accuracy, it suffers from inter-reader variability, and the time-consuming reporting process. This systematic review was registered on PROSPERO (ID CRD42023456044) and aims to [...] Read more.
Early detection of metastatic prostate cancer (mPCa) is crucial. Whilst the prostate-specific membrane antigen (PSMA) PET scan has high diagnostic accuracy, it suffers from inter-reader variability, and the time-consuming reporting process. This systematic review was registered on PROSPERO (ID CRD42023456044) and aims to evaluate AI’s ability to enhance reporting, diagnostics, and predictive capabilities for mPCa on PSMA PET scans. Inclusion criteria covered studies using AI to evaluate mPCa on PSMA PET, excluding non-PSMA tracers. A search was conducted on Medline, Embase, and Scopus from inception to July 2023. After screening 249 studies, 11 remained eligible for inclusion. Due to the heterogeneity of studies, meta-analysis was precluded. The prediction model risk of bias assessment tool (PROBAST) indicated a low overall risk of bias in ten studies, though only one incorporated clinical parameters (such as age, and Gleason score). AI demonstrated a high accuracy (98%) in identifying lymph node involvement and metastatic disease, albeit with sensitivity variation (62–97%). Advantages included distinguishing bone lesions, estimating tumour burden, predicting treatment response, and automating tasks accurately. In conclusion, AI showcases promising capabilities in enhancing the diagnostic potential of PSMA PET scans for mPCa, addressing current limitations in efficiency and variability. Full article
(This article belongs to the Special Issue “Cancer Metastasis” in 2023–2024)
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