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Cancer Metastasis in 2025–2026

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

Deadline for manuscript submissions: 31 July 2026 | Viewed by 5806

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Prof. Dr. Lance A. Liotta

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Department of Systems Biology, Center for Applied Proteomics and Molecular Medicine, George Mason University, 10900 University Boulevard, MS 4E3, Manassas, VA 20110, USA
Interests: proteomics; biotechnology; metastasis; personalized medicine
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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 Special 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 A. 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 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-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
invasion

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Published Papers (4 papers)

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Research

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16 pages, 1054 KB

Open AccessArticle

The Prognostic Impact of the Ki-67 Proliferation Index in Patients with Surgically Treated Spinal Metastases

by Saif-Eldin Abedellatif, Marija Janjic, Logman Khalafov, Harun Asoglu, Juliane Dittmer, Muriel Heimann, Mohammed Jaber, Haitham Alenezi, Marieta Ioana Toma, Matthias Schneider, Hartmut Vatter, Motaz Hamed and Mohammed Banat

Cancers 2026, 18(8), 1210; https://doi.org/10.3390/cancers18081210 - 10 Apr 2026

Viewed by 331

Abstract

Background: The prognostic assessment of patients with spinal metastases is primarily based on clinical and radiological parameters. Biological tumor characteristics such as the proliferation marker Ki-67 have prognostic relevance in various metastatic settings. This study aimed to evaluate the prognostic impact of the Ki-67 proliferation index on survival outcomes in patients undergoing surgery for spinal metastases. Methods: We included 166 patients who underwent surgical treatment for spinal metastases at our university clinic between 2015 and 2024. Clinical, functional, tumor-related, and perioperative variables were collected. Receiver operating characteristic (ROC) analysis was performed to evaluate the discriminatory ability of Ki-67, and comparisons were made between patient groups according to Ki-67 expression (≤20% vs. >20%). Results: Based on ROC analysis, Ki-67 demonstrated a moderate but significant predictive ability for 1-year mortality (area under the curve [AUC]: 0.69, p = 0.001). Patients with a Ki-67 index of >20% showed a significantly shorter overall survival than those with a lower Ki-67 index of ≤20% (median overall survival: 5.0 vs. 14.5 months, p < 0.001). One-year mortality was significantly higher in the high Ki-67 group (78.9% vs. 41.8%, p = 0.001). High Ki-67 expression was associated with more aggressive tumor characteristics but was not associated with increased perioperative morbidity. Conclusions: The Ki-67 proliferation index is a significant prognostic biomarker in surgically treated patients with spinal metastases. A Ki-67 index threshold of 20% identifies patients at increased risk of early mortality and significantly reduced overall survival. Full article

(This article belongs to the Special Issue Cancer Metastasis in 2025–2026)

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19 pages, 2879 KB

Open AccessArticle

Prevalence and Outcomes of HER2-Low Versus HER2-0 Status in Patients with Metastatic Breast Cancer

by Akshara Singareeka Raghavendra, Diane D. Liu, Senthil Damodaran, Sarah Pasyar, Yu Shen, Jason A. Mouabbi, Carlos H. Barcenas, Kelly K. Hunt and Debu Tripathy

Cancers 2026, 18(2), 253; https://doi.org/10.3390/cancers18020253 - 14 Jan 2026

Viewed by 726

Abstract

Background: HER2-low breast cancer (HER2 immunohistochemical [IHC] score 1+, or IHC 2+ without HER2 gene amplification) is distinct from HER2-positive and HER2-0 breast cancer (IHC 0), with a differing prognosis and specific therapeutic options. The DESTINY-Breast04 trial demonstrated notable efficacy of the HER2 antibody–drug conjugate trastuzumab deruxtecan over standard chemotherapy in patients with metastatic breast cancer (MBC) defined as HER2-low. More recently, the DESTINY-Breast06 trial confirmed this benefit in hormone receptor-positive and HER2-ultralow (less than 1+, but with ≤10% of infiltrating cancer cells showing incomplete and faint/weak membrane staining) cases, prompting re-evaluation of HER2 diagnostic thresholds and treatment strategies. Methods: Eligible patients were women with HER2-low or HER2-0 MBC evaluated at MD Anderson between January 2006 and January 2019. HER2-low was defined as either (1) IHC 1+ or (2) IHC 2+ and negative on fluorescence in situ hybridization. Multivariate logistic regression was used to evaluate distinct clinicopathologic features of patients with HER2-low status. Overall survival (OS) was estimated by the Kaplan–Meier method. Multivariate Cox proportional hazards regression was applied to assess the effects of covariates of interest on OS across different HER2 groups. Results: We included 3834 women: 2637 (69%) with recurrent and 1197 (31%) with de novo MBC; HER2-low disease was present in 1575 (60%) and 712 (59%), respectively. In de novo cases, higher nuclear grade was associated with HER2-low status (grade 2 vs. 1, OR = 2.02, p = 0.007; grade 3 vs. 1, OR = 1.87, p = 0.015), while recurrent cases were associated with ER-positivity (OR = 1.96, p < 0.001) and prior adjuvant radiotherapy (OR = 0.79, p = 0.007). Median OS was 3.2 years (95% CI 3.0–3.5). In de novo disease, Black race (HR = 1.48), metaplastic (HR = 3.15) or other non-ductal/lobular histologies (HR = 2.36), and grade 3 (HR = 1.67) predicted worse OS, whereas Hispanic ethnicity (HR = 0.74) and Other races (HR = 0.57), higher ER (HR = 0.48–0.41) and PR (HR = 0.72–0.53), and HER2-low status (HR = 0.77) conferred improved outcomes. In recurrent disease, Black race predicted worse OS (HR = 1.21, 95% CI 1.05–1.39), while Other race (HR = 0.78, 95% CI 0.62–0.97), higher ER (HR = 0.69–0.44) and PR (HR = 0.73–0.73), and HER2-low (HR = 0.89) were protective. HER2 discordance between primary and metastatic sites occurred in 38.8% of recurrent and 13.1% of de novo cases. Conclusions: HER2-low status was significantly associated with longer OS compared to HER2-0 status in both recurrent and de novo MBC cases. These real-world data help establish the prevalence of HER2-low status and its distinct outcomes. The discrepancy in HER2-low status between the primary tumor and metastatic sites highlights the potential for changes in HER2 expression over time, exploring the interaction between HER2-low breast cancer and the tumor microenvironment and emphasizing the importance of monitoring and reassessing HER2 status at various stages to guide treatment decisions effectively and the need for more quantitative and reproducible HER assays. Full article

(This article belongs to the Special Issue Cancer Metastasis in 2025–2026)

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17 pages, 1349 KB

Open AccessArticle

Status of Pulmonary Metastasectomy After PuLMiCC Trial: A Survey Amongst Oncologists, Gynecologists, Urologists and Dermatologists on Medical Needs for Local Therapy

by Daniel Baum, Markus Grafe, Rahel Decker, Lysann Rostock, Andreas Friedrich and Till Plönes

Cancers 2025, 17(24), 3959; https://doi.org/10.3390/cancers17243959 - 11 Dec 2025

Viewed by 787

Abstract

Background: The role of pulmonary metastasectomy has been increasingly questioned in the surgical community after the PulMiCC trial challenged its benefit in colorectal cancer. However, the view on pulmonary metastasectomy among people in non-surgical disciplines remains unclear. This study explored interdisciplinary attitudes toward pulmonary metastasectomy and identified the clinical expectations shaping its future role. Methods: An anonymous online survey of active board-certified physicians in oncology, urology, gynecology and dermatology was conducted (December 2024–June 2025). Twenty items covered attitudes to local ablative therapy, referral criteria, preferred modalities and future relevance. Group comparisons used Pearson’s χ²; ordinal ratings were compared by one-way ANOVA; associations were explored with Spearman’s ρ. Results: Of 2884 contacted physicians, 165 participated (≈5.7%), and 106 completed the questionnaire. All 106 (100%) endorsed local ablative therapy as meaningful; 92/106 (86.8%) favored routine integration into multimodal care. Surgical metastasectomy was selected by 49/106 (46.2%), SBRT was selected by 27/106 (25.5%) and image-guided ablation was selected by 7/106 (6.6%); preference for surgery differed by specialty (χ²(4) = 15.31, p = 0.004), while institutional availability (in-house thoracic surgery or radiation oncology) showed no association with selecting surgery or SBRT. Key referral determinants were number of lesions (105/106; 99.1%), anatomical location (86/106; 81.1%; p < 0.02 across specialties), and lesion size (81/106; 76.4%; p < 0.05); other factors showed no consistent inter-specialty differences. The perceived usefulness of metastasectomy was high (mode 8/10) and showed a weak, non-significant correlation with referral experience (ρ = 0.172, p = 0.077). Looking ahead, 46/106 (43.4%) anticipated a declining role of local ablative therapy with novel systemic therapies; interest in biomarker analysis from metastatic tissue compared to primary tumor tissue was very high 97/106 (91.5%). Conclusions: Local ablative therapy, particularly pulmonary metastasectomy, continues to be viewed as an integral and trusted element of metastatic disease management across specialties. Despite limited prospective evidence, clinicians maintain strong confidence in its clinical value and foresee its evolution toward biologically and patient-tailored indications. However, the interpretation of these findings is limited by a low response rate and potential selection bias toward European, academically affiliated respondents. To our knowledge, this is the first study to systematically capture perceptions of pulmonary metastasectomy among non-surgical oncology-related specialists. Full article

(This article belongs to the Special Issue Cancer Metastasis in 2025–2026)

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Review

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18 pages, 509 KB

Open AccessReview

Impact of Anti-HER2 Therapies on Overall Survival in Patients with HER2-Positive Metastatic Breast Cancer: Focusing on Intracranial Efficacy of Emerging Treatments

by Denise Drittone, Claudia Lucci, Luisa Esposito, Federica Mazzuca and Simona Pisegna

Cancers 2025, 17(21), 3520; https://doi.org/10.3390/cancers17213520 - 31 Oct 2025

Cited by 1 | Viewed by 3034

Abstract

Therapies targeting human epidermal growth factor receptor 2 (HER2) have substantially improved overall survival in patients with HER2-positive metastatic breast cancer. Approximately 31% of these patients develop brain metastases, representing a significant therapeutic challenge. This review classifies anti-HER2 therapies into three categories: monoclonal antibodies (MABs), antibody-drug conjugates (ADCs), and tyrosine kinase inhibitors (TKIs). The mechanisms of action and clinical impacts of these agents are examined, with particular attention to intracranial efficacy. The introduction of trastuzumab increased overall survival (OS) from 20.3 to 25.1 months compared to chemotherapy alone. The addition of pertuzumab further extended survival to 57.1 months, as demonstrated in the CLEOPATRA trial. Among ADCs, T-DM1 improved OS to 29.9 months versus 25.9 months in the EMILIA trial, while T-DXd extended OS to 52.6 months in DESTINY-Breast03. T-DXd also demonstrated notable intracranial activity, achieving a 64.9% objective response rate in patients with active brain metastases. In the HER2CLIMB trial, tucatinib reduced intracranial progression by 68% and improved OS (24.7 vs. 19.2 months) in patients with active brain metastases. Recent advances have increased median OS from approximately 20 months prior to trastuzumab to over 50 months with current therapies. Future research should focus on optimizing treatment sequencing, refining biomarker-driven approaches, and developing targeted strategies for brain metastases to further improve long-term survival outcomes. Full article

(This article belongs to the Special Issue Cancer Metastasis in 2025–2026)

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