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Cancers
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Colorectal Cancer Metastasis (Volume II)
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Colorectal Cancer Metastasis (Volume II)

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

Deadline for manuscript submissions: closed (25 May 2025) | Viewed by 2913

Special Issue Editors

Dr. Massimiliano Berretta

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Guest Editor
Department of Clinical and Experimental Medicine, University of Messina, 98121 Messina, Italy
Interests: colorectal cancer; breast cancer; complementary and alternative medicine
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Alessandro Ottaiano

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Guest Editor
SSD-Innovative Therapies for Abdominal Metastases, Department of Abdominal Oncology, Istituto Nazionale Tumori di Napoli IRCCS “G. Pascale”, via M. Semmola, 80131 Naples, Italy
Interests: cancer genetics; gastro-intestinal oncology; oligo-metastatic disease; molecular oncology; precision oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Mariachiara Santorsola

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Guest Editor
Istituto Nazionale Tumori IRCCS–Fondazione G Pascale, Napoli, Naples, Italy
Interests: cancer genetics; translational studies; molecular oncology; oligometastatic disease
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

This collection is the second edition of the previous one, “Colorectal Cancer Metastasis”: https://www.mdpi.com/journal/cancers/special_issues/3C

The primary objective of the inaugural edition of this Special Issue was to stimulate interdisciplinary research on the intricate genetics of metastatic colorectal cancer (mCRC), providing insights into its prognosis, predictive markers, and cancer plasticity.

In contrast, the second edition is geared towards furthering our comprehension of mCRC to facilitate precision medicine and treatment design. Over recent years, substantial strides have been made in the management of mCRC. In addition to traditional chemotherapy agents, such as fluorouracil, irinotecan, and oxaliplatin, a novel class of drugs has emerged, encompassing biologically targeted agents like cetuximab, panitumumab, aflibercept, regorafenib, and encorafenib, alongside innovative “non-selective” mechanism-of-action oral medications like capecitabine and trifluridine/tipiracil. Nonetheless, it is important to note that immunotherapy remains applicable to only a small subset of patients with microsatellite instability, constituting less than 5% of cases.

While numerous therapeutic options remain under investigation, lacking widespread consensus regarding their effectiveness or regulatory approval, it is evident that mCRC has not experienced the same level of progress in systemic therapy management observed in other cancer types, such as lung and breast cancer. This disparity underscores the intricacy of the disease, marked by biological diversity and a relatively constrained understanding of its molecular drivers.

Acknowledging the pressing need for further progress in the field, this second edition of the Special Issue “Colorectal Cancer Metastasis” aspires to contribute to the existing body of knowledge by promoting research that can potentially lead to the discovery of new treatments and therapeutic strategies (including treatment sequences, real-world clinical case series, and patient selection criteria) for mCRC. We invite submissions of scientific articles to facilitate more profound insights into this challenging condition.

Articles that solely comprise bioinformatics or computational analyses of publicly available databases will not be considered for acceptance. We welcome submissions of analyses and studies that originate from real-world clinical practice and independent patient cohorts. Additionally, we highly value and encourage the submission of review articles.

Dr. Massimiliano Berretta
Prof. Dr. Alessandro Ottaiano
Dr. Mariachiara Santorsola
Guest Editors

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

  • colorectal cancer
  • genetics
  • epigenetics
  • metastases
  • prognosis
  • cancer evolution
  • precision medicine

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Published Papers (3 papers)

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Research

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11 pages, 1515 KiB  
Article
RAS-Beppu Classification: A New Recurrence Risk Classification System Incorporating the Beppu Score and RAS Status for Colorectal Liver Metastases
by Takuya Tajiri, Kosuke Mima, Toru Beppu, Hiromitsu Hayashi, Taichi Horino, Yuki Adachi, Katsunori Imai, Toshiro Masuda, Yuji Miyamoto and Masaaki Iwatsuki
Cancers 2025, 17(4), 640; https://doi.org/10.3390/cancers17040640 - 14 Feb 2025
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Abstract
Background: Preoperative recurrence risk stratification for colorectal liver metastases (CRLM) undergoing hepatectomy is essential when designing a treatment strategy. We developed a Beppu classification system consisting of three risk groups and found that the RAS mutation increased risk in low- and moderate-risk [...] Read more.
Background: Preoperative recurrence risk stratification for colorectal liver metastases (CRLM) undergoing hepatectomy is essential when designing a treatment strategy. We developed a Beppu classification system consisting of three risk groups and found that the RAS mutation increased risk in low- and moderate-risk patients. Methods: A total of 173 patients undergoing initial hepatectomy for CRLM between 2004 and 2020 were analyzed. Disease-free survival (DFS) and overall survival (OS) were assessed. Patients in the low- and moderate-risk groups of the Beppu classification with RAS mutations were moved into the moderate- and high-risk groups, respectively, in the RAS-Beppu classification. Results: The DFS curves of the three risk groups in the Beppu and RAS-Beppu classification were significantly different. Five-year DFS rates were 57%, 31%, and 16% in the RAS-Beppu classification of low-, moderate-, and high-risk groups, respectively. With multivariate analysis, Beppu classifications (p = 0.0017) and RAS-Beppu classifications (p = 0.0002) were independent prognostic factors for DFS. The RAS-Beppu classification showed higher hazard ratios than the Beppu classification, as well as the genetic and morphological evaluation score and the modified clinical risk score, which include the RAS status. The hazard ratios in the RAS-Beppu classification were significant in all two-group comparisons (2.22 for moderate vs. low, 3.48 for high vs. low, and 1.70 for high vs. moderate). The multivariate analysis of OS showed benefits of the RAS-Beppu classification in the high- vs. low-risk and high- vs. moderate-risk comparisons. Conclusions: The RAS-Beppu classification using standard parameters is a novel suitable tool for predicting recurrence risk before liver resection. Full article
(This article belongs to the Special Issue Colorectal Cancer Metastasis (Volume II))
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11 pages, 1871 KiB  
Article
Relationship of Desmoplastic Reaction and Tumour Budding in Primary and Lung Metastatic Lesions of Colorectal Cancer and Their Prognostic Significance
by Toshinori Kobayashi, Mitsuaki Ishida, Hiroshi Matsui, Hiroki Uehara, Shoichiro I, Norikazu Yamada, Yuto Igarashi, Chie Hagiwara, Yoshihiro Mori, Yohei Taniguchi, Tomohito Saito, Haruaki Hino, Yoshinobu Hirose, Tomohiro Murakawa and Jun Watanabe
Cancers 2025, 17(4), 583; https://doi.org/10.3390/cancers17040583 - 8 Feb 2025
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Abstract
Background/Objectives: Histopathological indicators, including desmoplastic reaction (DR) and tumour budding (TB), are significant prognostic indicators for metastatic liver lesions in patients with colorectal cancer (CRC). However, the relationship of DR and TB in primary CRC and metastatic lung lesions and their prognostic significance [...] Read more.
Background/Objectives: Histopathological indicators, including desmoplastic reaction (DR) and tumour budding (TB), are significant prognostic indicators for metastatic liver lesions in patients with colorectal cancer (CRC). However, the relationship of DR and TB in primary CRC and metastatic lung lesions and their prognostic significance has not yet been examined. This study aimed to elucidate the association of DR and TB in primary CRC and metastatic lung lesions. Methods: Patients with pT3 or pT4 CRC with lung metastasis who underwent surgical resection of the primary CRC and synchronous or metachronous metastatic lung lesions were enrolled. DR was classified into immature (IM) and non-IM types, and TB was classified into TB1 (<4 buds), TB2 (5–9 buds) and TB3 (≥10 buds) in both the primary CRC and metastatic lung lesions. Results: Overall, 40 patients with CRC (males, 21; females, 19; median age, 70 years; right-side colon, 6; left-side colon, 9; rectum, 25; pT3, 31; pT4, 9) were evaluated. Six and thirty-four patients were classified as having IM and non-IM DR in the metastatic lung lesions, respectively. Thirty-one, seven, and two patients were classified as having TB1, TB2, and TB3, respectively. There was no significant correlation between primary and lung metastatic lesions for DR (κ = 0.08, p = 0.086), whereas TB demonstrated a moderate correlation (κ = 0.47, p = 0.015). The presence of IM DR and TB2/3 in metastatic lung lesions significantly correlated with poor overall survival (p = 0.0020 and 0.044, respectively). Conclusions: histological indicators of metastatic lung lesions in CRC may provide important prognostic information for better patient care. Full article
(This article belongs to the Special Issue Colorectal Cancer Metastasis (Volume II))
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Review

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13 pages, 3775 KiB  
Review
Histotripsy of Liver Tumors: Patient Selection, Ethical Discussions, and How We Do It
by Melis Uysal, Chase J. Wehrle, Sangeeta Satish, Emily Knott, Hanna Hong, Erlind Allkushi, Andrea Schlegel, Eren Berber, Federico Aucejo, JaeKeun Kim and David C. H. Kwon
Cancers 2025, 17(7), 1100; https://doi.org/10.3390/cancers17071100 - 25 Mar 2025
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Abstract
Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced [...] Read more.
Liver malignancies, both primary and metastatic tumors, are a major cause of cancer-related mortality. Colorectal cancer alone results in liver metastases in nearly 50% of patients, with approximately 85% presenting with unresectable disease. Similarly, hepatocellular carcinoma and intrahepatic cholangiocarcinoma frequently present at advanced stages, limiting curative options. Systemic therapies provide modest survival benefits, underscoring the need for alternative treatments. Locoregional approaches, such as thermal ablation and chemoembolization, while effective, have notable limitations, including invasiveness, peri-procedural risks, and the requirement to interrupt systemic treatments. Histotripsy is a novel, non-invasive method that uses focused ultrasound-induced cavitation to enable precise tumor ablation without heat or radiation. Our institution utilizes a multidisciplinary tumor board approach to evaluate patients for histotripsy, particularly in cases involving unresectable disease, complex surgical candidacy, palliative intent related to disease control and symptom management, or as bridging therapy for transplantation. Early results, including preclinical data and the THERESA and #HOPE4LIVER trials, highlight its efficacy in treating liver tumors with minimal complications. This review outlines institutional protocols for histotripsy, covering pre- and post-procedural management, along with ethical considerations of current treatment paradigms. As a patient-centered approach, histotripsy offers a novel treatment option with a favorable safety profile and compatibility with systemic therapies. Full article
(This article belongs to the Special Issue Colorectal Cancer Metastasis (Volume II))
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