Cancers

Review

32 pages, 1209 KiB

Open AccessReview

The Role of Reactive Oxygen Species in Colorectal Cancer Initiation and Progression: Perspectives on Theranostic Approaches

by Teresa Catalano, Federico Selvaggi, Roberto Cotellese and Gitana Maria Aceto

Cancers 2025, 17(5), 752; https://doi.org/10.3390/cancers17050752 - 22 Feb 2025

Viewed by 1091

Abstract

Altered levels of reactive oxygen species (ROS) are recognized as one of the key factors in mediating tumor cell survival in the tissue microenvironment, where they play a role in the initiation, progression and recurrence/relapse of colorectal cancer (CRC). Tumor cells can adapt [...] Read more.

Altered levels of reactive oxygen species (ROS) are recognized as one of the key factors in mediating tumor cell survival in the tissue microenvironment, where they play a role in the initiation, progression and recurrence/relapse of colorectal cancer (CRC). Tumor cells can adapt to oxidative stress (OS) using genetic or metabolic reprogramming in the long or short term. In addition, tumor cells defend themselves through positive regulation of antioxidant molecules, enhancing ROS-driven proliferation. Balanced oxidative eustress levels can influence chemotherapy resistance, allowing tumor cells to survive treatment. Secondary effects of chemotherapy include increased ROS production and redox stress, which can kill cancer cells and eliminate drug resistance. Anticancer treatments based on manipulating ROS levels could represent the gold standard in CRC therapy. Therefore, exploring the modulation of the response to OS in deregulated signaling pathways may lead to the development of new personalized CRC treatments to overcome therapy resistance. In this review, we explore the role of ROS in the initiation and progression of CRC and their diagnostic implications as biomarkers of disease. Furthermore, we focused on the involvement of ROS in different CRC therapeutic options, such as surgery, radiotherapy, theranostic imaging, chemotherapy and immunotherapy and other precision medicine approaches. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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38 pages, 2883 KiB

Open AccessReview

Hepatic Iron Overload and Hepatocellular Carcinoma: New Insights into Pathophysiological Mechanisms and Therapeutic Approaches

by Elena Chatzikalil, Konstantinos Arvanitakis, Georgios Kalopitas, Matilda Florentin, Georgios Germanidis, Theocharis Koufakis and Elena E. Solomou

Cancers 2025, 17(3), 392; https://doi.org/10.3390/cancers17030392 - 24 Jan 2025

Viewed by 2222

Abstract

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is rising in global incidence and mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disease, is strongly linked to metabolic conditions that can progress to [...] Read more.

Hepatocellular carcinoma (HCC), the most common form of primary liver cancer, is rising in global incidence and mortality. Metabolic dysfunction-associated steatotic liver disease (MASLD), one of the leading causes of chronic liver disease, is strongly linked to metabolic conditions that can progress to liver cirrhosis and HCC. Iron overload (IO), whether inherited or acquired, results in abnormal iron hepatic deposition, significantly impacting MASLD development and progression to HCC. While the pathophysiological connections between hepatic IO, MASLD, and HCC are not fully understood, dysregulation of glucose and lipid metabolism and IO-induced oxidative stress are being investigated as the primary drivers. Genomic analyses of inherited IO conditions reveal inconsistencies in the association of certain mutations with liver malignancies. Moreover, hepatic IO is also associated with hepcidin dysregulation and activation of ferroptosis, representing promising targets for HCC risk assessment and therapeutic intervention. Understanding the relationship between hepatic IO, MASLD, and HCC is essential for advancing clinical strategies against liver disease progression, particularly with recent IO-targeted therapies showing potential at improving liver biochemistry and insulin sensitivity. In this review, we summarize the current evidence on the pathophysiological association between hepatic IO and the progression of MASLD to HCC, underscoring the importance of early diagnosis, risk stratification, and targeted treatment for these interconnected conditions. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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16 pages, 681 KiB

Open AccessReview

Exploring Chemoprevention in Colorectal Cancer for Patients with Inflammatory Bowel Disease: Mechanisms of Action and Clinical Aspects

by Fotios S. Fousekis, Konstantinos Mpakogiannis, Panagiotis Filis, Alexandros Skamnelos, Dimitrios K. Christodoulou, Davide Mauri and Konstantinos H. Katsanos

Cancers 2025, 17(2), 229; https://doi.org/10.3390/cancers17020229 - 12 Jan 2025

Viewed by 1542

Abstract

Background: Inflammatory bowel diseases (IBDs) have been associated with a higher risk of colorectal cancer (CRC) development and chronic colonic inflammation seems to have a critical role in the pathogenesis of CRC in patients suffering from IBD. In respect to that, surveillance colonoscopy [...] Read more.

Background: Inflammatory bowel diseases (IBDs) have been associated with a higher risk of colorectal cancer (CRC) development and chronic colonic inflammation seems to have a critical role in the pathogenesis of CRC in patients suffering from IBD. In respect to that, surveillance colonoscopy at regular intervals is recommended in patients with colitis. Objective: This review aims to explore the chemopreventive potential of a range of agents, including mesalazine, thiopurines, anti-TNF agents, statins, ursodeoxycholic acid, aspirin, folic acid, and nutraceuticals. Results: These agents target inflammation, oxidative stress, and oncogenic pathways, thereby offering the potential to reduce the risk of CRC in patients with IBD. Anti-TNF agents, such as infliximab and adalimumab, not only reduce colonic inflammation, but also play a protective role against CRC by lessening the carcinogenic effects associated with prolonged inflammatory processes. Furthermore, mesalazine and thiopurines have demonstrated established efficacy, while newer biologics, including interleukin inhibitors, show promising advancements. Although nutraceuticals and dietary interventions require further clinical validation, they offer additional possibilities for non-pharmacological prevention. Conclusion: Despite progress, knowledge gaps persist regarding the long-term safety, optimal dosing, and combined use of these agents. A significant reduction in the incidence of CRC in patients with IBD could be achieved by advancing chemoprevention and personalizing strategies. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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29 pages, 1367 KiB

Open AccessReview

Current Paradigm and Future Directions in the Management of Nodal Disease in Locally Advanced Cervical Cancer

by Elki Sze-Nga Cheung and Philip Yuguang Wu

Cancers 2025, 17(2), 202; https://doi.org/10.3390/cancers17020202 - 9 Jan 2025

Cited by 1 | Viewed by 1094

Abstract

Approximately 36% of patients with cervical cancer present with regional nodal metastasis at diagnosis, which is associated with adverse survival outcomes after definitive treatment. In the modern era of chemoradiotherapy (CRT) and image-guided adaptive brachytherapy (IGABT), where excellent local control is achieved for [...] Read more.

Approximately 36% of patients with cervical cancer present with regional nodal metastasis at diagnosis, which is associated with adverse survival outcomes after definitive treatment. In the modern era of chemoradiotherapy (CRT) and image-guided adaptive brachytherapy (IGABT), where excellent local control is achieved for patients with locally advanced cervical cancer (LACC), nodal failure remains a major challenge to cure. To optimize treatment outcomes for node-positive LACC and reduce the incidence of nodal failure, various treatment approaches have been explored, including methods of surgical nodal staging or dissection, RT dose escalation strategies, such as intensity-modulated radiotherapy (IMRT) with simultaneous integrated boost (SIB) to involved nodes, and elective treatment of subclinical para-aortic (PAO) disease. Additionally, there is growing interest in emerging precision RT techniques, such as magnetic resonance-guided radiotherapy (MRgRT) and proton therapy, which may allow for further improvement in the therapeutic ratio. This review outlines the various methods of detection of nodal metastasis, treatment options for node-positive LACC, techniques of nodal radiotherapy and their clinical evidence in efficacy and toxicity profiles. Furthermore, recent advances in systemic therapy and promising novel therapeutic directions that may shape the management of node-positive LACC are discussed. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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43 pages, 8085 KiB

Open AccessReview

Very High-Energy Electron Therapy Toward Clinical Implementation

by Costanza Maria Vittoria Panaino, Simona Piccinini, Maria Grazia Andreassi, Gabriele Bandini, Andrea Borghini, Marzia Borgia, Angelo Di Naro, Luca Umberto Labate, Eleonora Maggiulli, Maurizio Giovanni Agostino Portaluri and Leonida Antonio Gizzi

Cancers 2025, 17(2), 181; https://doi.org/10.3390/cancers17020181 - 8 Jan 2025

Viewed by 2015

Abstract

The use of very high energy electron (VHEE) beams, with energies between 50 and 400 MeV, has drawn considerable interest in radiotherapy due to their deep tissue penetration, sharp beam edges, and low sensitivity to tissue density. VHEE beams can be precisely steered [...] Read more.

The use of very high energy electron (VHEE) beams, with energies between 50 and 400 MeV, has drawn considerable interest in radiotherapy due to their deep tissue penetration, sharp beam edges, and low sensitivity to tissue density. VHEE beams can be precisely steered with magnetic components, positioning VHEE therapy as a cost-effective option between photon and proton therapies. However, the clinical implementation of VHEE therapy (VHEET) requires advances in several areas: developing compact, stable, and efficient accelerators; creating sophisticated treatment planning software; and establishing clinically validated protocols. In addition, the perspective of VHEE to access ultra-high dose–rate regime presents a promising avenue for the practical integration of FLASH radiotherapy of deep tumors and metastases with VHEET (FLASH-VHEET), enhancing normal tissue sparing while maintaining the inherent dosimetric advantages of VHEET. However, FLASH-VHEET systems require validation of time-dependent dose parameters, thus introducing additional technological challenges. Here, we discuss recent progress in VHEET research, focusing on both conventional and FLASH modalities, and covering key aspects including dosimetric properties, radioprotection, accelerator technology, beam focusing, radiobiological effects, and clinical outcomes. Furthermore, we comprehensively analyze initial VHEET in silico studies on coverage across various tumor sites. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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33 pages, 1875 KiB

Open AccessReview

New Relevant Evidence in Cholangiocarcinoma Biology and Characterization

by Nunzia Porro, Elena Spínola-Lasso, Mirella Pastore, Alessandra Caligiuri, Luca di Tommaso, Fabio Marra and Alessandra Gentilini

Cancers 2024, 16(24), 4239; https://doi.org/10.3390/cancers16244239 - 19 Dec 2024

Viewed by 1225

Abstract

Among solid tumors, cholangiocarcinoma (CCA) emerges as one of the most difficult to eradicate. The silent and asymptomatic nature of this tumor, particularly in its early stages, as well as the high heterogeneity at genomic, epigenetic, and molecular levels delay the diagnosis, significantly [...] Read more.

Among solid tumors, cholangiocarcinoma (CCA) emerges as one of the most difficult to eradicate. The silent and asymptomatic nature of this tumor, particularly in its early stages, as well as the high heterogeneity at genomic, epigenetic, and molecular levels delay the diagnosis, significantly compromising the efficacy of current therapeutic options and thus contributing to a dismal prognosis. Extensive research has been conducted on the molecular pathobiology of CCA, and recent advances have been made in the classification and characterization of new molecular targets. Both targeted therapy and immunotherapy have emerged as effective and safe strategies for various types of cancers, demonstrating potential benefits in advanced CCA. Furthermore, the deeper comprehension of the cellular and molecular components in the tumor microenvironment (TME) has opened up possibilities for new innovative treatment methods. This review discusses recent evidence in the characterization and molecular biology of CCA, highlighting novel possible druggable targets. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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Graphical abstract

29 pages, 4275 KiB

Open AccessReview

Artificial Intelligence-Assisted Stimulated Raman Histology: New Frontiers in Vibrational Tissue Imaging

by Manu Krishnan Krishnan Nambudiri, V. G. Sujadevi, Prabaharan Poornachandran, C. Murali Krishna, Takahiro Kanno and Hemanth Noothalapati

Cancers 2024, 16(23), 3917; https://doi.org/10.3390/cancers16233917 - 22 Nov 2024

Viewed by 2121

Abstract

Frozen section biopsy, introduced in the early 1900s, still remains the gold standard methodology for rapid histologic evaluations. Although a valuable tool, it is labor-, time-, and cost-intensive. Other challenges include visual and diagnostic variability, which may complicate interpretation and potentially compromise the [...] Read more.

Frozen section biopsy, introduced in the early 1900s, still remains the gold standard methodology for rapid histologic evaluations. Although a valuable tool, it is labor-, time-, and cost-intensive. Other challenges include visual and diagnostic variability, which may complicate interpretation and potentially compromise the quality of clinical decisions. Raman spectroscopy, with its high specificity and non-invasive nature, can be an effective tool for dependable and quick histopathology. The most promising modality in this context is stimulated Raman histology (SRH), a label-free, non-linear optical process which generates conventional H&E-like images in short time frames. SRH overcomes limitations of conventional Raman scattering by leveraging the qualities of stimulated Raman scattering (SRS), wherein the energy gets transferred from a high-power pump beam to a probe beam, resulting in high-energy, high-intensity scattering. SRH’s high resolution and non-requirement of preprocessing steps make it particularly suitable when it comes to intrasurgical histology. Combining SRH with artificial intelligence (AI) can lead to greater precision and less reliance on manual interpretation, potentially easing the burden of the overburdened global histopathology workforce. We review the recent applications and advances in SRH and how it is tapping into AI to evolve as a revolutionary tool for rapid histologic analysis. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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22 pages, 2221 KiB

Open AccessReview

An Overview for Clinicians on Intraductal Papillary Mucinous Neoplasms (IPMNs) of the Pancreas

by Dimitrios Moris, Ioannis Liapis, Piyush Gupta, Ioannis A. Ziogas, Georgia-Sofia Karachaliou, Nikolaos Dimitrokallis, Brian Nguyen and Pejman Radkani

Cancers 2024, 16(22), 3825; https://doi.org/10.3390/cancers16223825 - 14 Nov 2024

Viewed by 1717

Abstract

Currently, there is no reliable method of discerning between low-risk and high-risk intraductal papillary mucinous neoplasms (IPMNs). Operative resection is utilized in an effort to resect those lesions with high-grade dysplasia (HGD) prior to the development of invasive disease. The current guidelines recommend [...] Read more.

Currently, there is no reliable method of discerning between low-risk and high-risk intraductal papillary mucinous neoplasms (IPMNs). Operative resection is utilized in an effort to resect those lesions with high-grade dysplasia (HGD) prior to the development of invasive disease. The current guidelines recommend resection for IPMN that involve the main pancreatic duct. Resecting lesions with HGD before their progression to invasive disease and the avoidance of resection in those patients with low-grade dysplasia is the optimal clinical scenario. Therefore, the importance of developing preoperative models able to discern HGD in IPMN patients cannot be overstated. Low-risk patients should be managed with nonsurgical treatment options (typically MRI surveillance), while high-risk patients would undergo resection, hopefully prior to the formation of invasive disease. Current research is evolving in multiple directions. First, there is an ongoing effort to identify reliable markers for predicting malignant transformation of IPMN, mainly focusing on genomic and transcriptomic data from blood, tissue, and cystic fluid. Also, multimodal models of combining biomarkers with clinical and radiographic data seem promising for providing robust and accurate answers of risk levels for IPMN patients. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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16 pages, 1068 KiB

Open AccessReview

The Influence of Microbiota on Breast Cancer: A Review

by Cara-Xenia-Rafaela Neagoe, Mihaela Ionică, Octavian Constantin Neagoe and Adrian Pavel Trifa

Cancers 2024, 16(20), 3468; https://doi.org/10.3390/cancers16203468 - 13 Oct 2024

Cited by 2 | Viewed by 2700

Abstract

Breast cancer remains one of the leading causes of death among women worldwide, and recent research highlights its growing connection to alterations in the microbiota. This review delves into the intricate relationship between microbiotas and breast cancer, exploring its presence in healthy breast [...] Read more.

Breast cancer remains one of the leading causes of death among women worldwide, and recent research highlights its growing connection to alterations in the microbiota. This review delves into the intricate relationship between microbiotas and breast cancer, exploring its presence in healthy breast tissue, its changes during cancer progression, and its considerable impact on both the tumor microenvironment (TME) and the tumor immune microenvironment (TIME). We extensively analyze how the microbiota influences cancer growth, invasion, metastasis, resistance to drugs, and the evasion of the immune system, with a special focus on its effects on the TIME. Furthermore, we investigate distinct microbial profiles associated with the four primary molecular subtypes of breast cancer, examining how the microbiota in tumor tissues compares with that in adjacent normal tissues. Emerging studies suggest that microbiotas could serve as valuable diagnostic and prognostic biomarkers, as well as targets for therapy. This review emphasizes the urgent need for further research to improve strategies for breast cancer prevention, diagnosis, and treatment. By offering a detailed examination of the microbiota’s critical role in breast cancer, this review aims to foster the development of novel microbiota-based approaches for managing the disease. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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27 pages, 965 KiB

Open AccessEditor’s ChoiceReview

Clinical Prediction Models for Prognosis of Colorectal Liver Metastases: A Comprehensive Review of Regression-Based and Machine Learning Models

by Stamatios Kokkinakis, Ioannis A. Ziogas, Jose D. Llaque Salazar, Dimitrios P. Moris and Georgios Tsoulfas

Cancers 2024, 16(9), 1645; https://doi.org/10.3390/cancers16091645 - 25 Apr 2024

Cited by 4 | Viewed by 2159

Abstract

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of “high-risk” patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to [...] Read more.

Colorectal liver metastasis (CRLM) is a disease entity that warrants special attention due to its high frequency and potential curability. Identification of “high-risk” patients is increasingly popular for risk stratification and personalization of the management pathway. Traditional regression-based methods have been used to derive prediction models for these patients, and lately, focus has shifted to artificial intelligence-based models, with employment of variable supervised and unsupervised techniques. Multiple endpoints, like overall survival (OS), disease-free survival (DFS) and development or recurrence of postoperative complications have all been used as outcomes in these studies. This review provides an extensive overview of available clinical prediction models focusing on the prognosis of CRLM and highlights the different predictor types incorporated in each model. An overview of the modelling strategies and the outcomes chosen is provided. Specific patient and treatment characteristics included in the models are discussed in detail. Model development and validation methods are presented and critically appraised, and model performance is assessed within a proposed framework. Full article

(This article belongs to the Special Issue Advanced Research in Oncology in 2024)

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