Feature Paper in Section “Cancer Therapy” in 2024

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

Deadline for manuscript submissions: 31 December 2024 | Viewed by 10335

Special Issue Editors


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Guest Editor
1. Section of Gastrointestinal Oncology—Houston Methodist Neal Cancer Center and Institute of Academic Medicine, 6445 Fannin, OPC-24, Houston, TX 77030, USA
2. Houston Methodist Research Institute, Houston, TX 77030, USA
Interests: transplant oncology; liver cancer; cholangiocarcinoma; targeted therapy; immunotherapy
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Guest Editor
1. Section of Nephrology, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2. Director of Clinical Research, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
Interests: onco-nephrology; transplant oncology; immunotherapy; immunotherapy toxicity; renal transplant

Special Issue Information

Dear Colleagues,

As a result of the development and improvement of modalities for systematic and localized treatment routes, the field of oncology that was established has undergone a complete revolution. To effectively manage the progression of cancer, it is essential to have therapeutic approaches that are both precise and targeted, as well as those that are particular to the affected area and may be utilized at an early stage. The major method that is utilized for people who are qualified to undergo surgical removal of the tumor is the utilization of these. Chemotherapy is a medication that is frequently used in the treatment of cancer, yet it is notorious for the significant toxicity that it causes in patients. On the other hand, as a pharmaceutical intervention, it is currently being utilized increasingly frequently in conjunction with immunotherapy. The effectiveness of immunotherapy is based on its capacity to strengthen the immune system of the host, which makes it an appropriate supplement to the standard of care that has been established for long-term treatment. In addition, immunotherapy has undergone substantial changes, particularly since the Food and Drug Administration (FDA) authorized it for the treatment of more advanced cancers. Additionally, the increasing validity and effectiveness of immunotherapies have been demonstrated in recent clinical research trials conducted all over the world with the purpose of improving oncology treatments. For the purpose of improving both survival rates and quality of life in the field of cancer, it is essential to continue developing each therapy technique. This Special Issue will discuss the innovation of recent therapy, chemo- and immunotherapy developments and specializations, and targeted therapy.

Dr. Abdullah Esmail
Dr. Ala Abudayyeh
Guest Editors

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Keywords

  • chemotherapy
  • immunotherapy for cancer
  • oncology
  • systemic treatment and targeted therapy

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Published Papers (10 papers)

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Research

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12 pages, 1462 KiB  
Article
The Importance of Patient Systemic Health Status in High-Grade Chondrosarcoma Prognosis: A National Multicenter Study
by Veroniek M. van Praag, Dominique Molenaar, Guus A. H. Tendijck, Gerard R. Schaap, Paul C. Jutte, Ingrid C. M. van der Geest, Marta Fiocco and Michiel A. J. van de Sande
Cancers 2024, 16(20), 3484; https://doi.org/10.3390/cancers16203484 - 14 Oct 2024
Viewed by 513
Abstract
Background: Due to the relatively advanced age and high mortality rate of patients with high-grade chondrosarcoma (CS), it is important to holistically assess patient- and tumor characteristics in multidisciplinary team and shared decision-making with regard to treatment options. While current prognostic models include [...] Read more.
Background: Due to the relatively advanced age and high mortality rate of patients with high-grade chondrosarcoma (CS), it is important to holistically assess patient- and tumor characteristics in multidisciplinary team and shared decision-making with regard to treatment options. While current prognostic models include multiple tumor and treatment characteristics, the only patient characteristics that are commonly included are age and gender. Based on clinical experience, we believe that factors related to patient preoperative systemic health status such as the American Society of Anesthesiologists (ASA) score may be equally important prognostic factors for overall survival (OS). Methods: A retrospective nationwide cohort study was identified from four specialized bone sarcoma centers in The Netherlands. Patients with a primary CS grade II, III, and dedifferentiated CS were eligible. Prognostic factors including age at presentation, gender, ASA score, CVD, tobacco use, BMI, histological tumor grade, tumor size, pathological fracture, presentation after unplanned excision, type of surgery and surgical margin were evaluated. The outcome measure was OS at the time of surgery. The Kaplan–Meier methodology was employed to estimate OS; a log-rank test was used to assess the difference in survival. To study the impact of prognostic factors on OS, a multivariate Cox proportional hazard regression model was estimated. Results: In total, 249 patients were eligible for this study, and 89 were deceased at the end of follow-up. In multivariate analysis, histological grade (HR 2.247, 95% CI 1.334–3.783), ASA score III (HR 2.615, 95% CI 1.145–5.976, vs. ASA I), and age per year (HR: 1.025, 95% CI 1.004–1.045) were negatively associated with OS. No association was found between tobacco use, BMI, gender or cardiovascular disease and OS in this cohort. Pathological fracture and tumor size were only associated with OS in univariate analysis. Conclusions: This multicenter study is the first on sarcomas to include ASA in a prognostic model. Results show that ASA score as a proxy for patients’ systemic health status should be included when providing a prognosis for patients with a high-grade primary CS, besides the conventional risk factors such as tumor grade and age. Specifically, severe systemic disease (ASA score III) is a strong negative predictor. Conversely, we found no difference in OS between ASA scores I and II. These findings aid multidisciplinary team and shared decision-making with regard to these complex sarcoma patients that often require life-changing surgeries. Level of Evidence: Prognostic level III. See the instructions for authors for the complete description of levels of evidence. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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16 pages, 2365 KiB  
Article
Optimizing Siglec-8-Directed Immunotherapy for Eosinophilic and Mast Cell Disorders
by Sheryl Y. T. Lim, Jenny Huo, George S. Laszlo, Frances M. Cole, Allie R. Kehret, Junyang Li, Margaret C. Lunn-Halbert, Jasmyn L. Persicke, Peter B. Rupert, Roland K. Strong and Roland B. Walter
Cancers 2024, 16(20), 3476; https://doi.org/10.3390/cancers16203476 - 14 Oct 2024
Viewed by 581
Abstract
Background/Objective: Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily [...] Read more.
Background/Objective: Current treatments for eosinophilic and mast cell disorders are often ineffective. One promising target to improve outcomes is sialic acid-binding immunoglobulin-like lectin-8 (Siglec-8). As limitations, there are few Siglec-8 monoclonal antibodies (mAbs) available to date, and Siglec-8-directed treatments have so far primarily focused on unconjugated mAbs, which may be inadequate, especially against mast cells. Methods: Here, we used transgenic mice to raise a diverse panel of fully human mAbs that either recognize the V-set domain, membrane-distal C2-set domain, or membrane-proximal C2-set domain of full-length Siglec-8 as a basis for novel therapeutics. Results: All mAbs were efficiently internalized into Siglec-8-expressing cells, suggesting their potential to deliver cytotoxic payloads. Tool T cell-engaging bispecific antibodies (BiAbs) and chimeric antigen receptor (CAR)-modified natural killer (NK) cells using single-chain variable fragments from Siglec-8 mAbs showed highly potent cytolytic activity against Siglec-8-positive cells even in cases of very low target antigen abundance, whereas they elicited no cytolytic activity against Siglec-8-negative target cells. Siglec-8V-set-directed T cell-engaging BiAbs and Siglec-8V-set-directed CAR-modified NK cells induced substantially greater cytotoxicity against cells expressing an artificial smaller Siglec-8 variant containing only the V-set domain than cells expressing full-length Siglec-8, consistent with the notion that targeting membrane-proximal epitopes enhances effector functions of Siglec-8 antibody-based therapeutics. Indeed, unconjugated Siglec-8C2-set mAbs, Siglec-8C2-set-directed T cell-engaging BiAbs, and Siglec-8C2-set-directed CAR-modified NK cells showed high antigen-specific cytolytic activity against Siglec-8-positive human cell lines and primary patient eosinophils. Conclusions: Together, these data demonstrate Siglec-8-directed immunotherapies can be highly potent, supporting their further development for eosinophilic and mast cell disorders. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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19 pages, 4792 KiB  
Article
Curcumin-Dichloroacetate Hybrid Molecule as an Antitumor Oral Drug against Multidrug-Resistant Advanced Bladder Cancers
by Kunj Bihari Gupta, Truett L. Taylor, Siva S. Panda, Muthusamy Thangaraju and Bal. L. Lokeshwar
Cancers 2024, 16(17), 3108; https://doi.org/10.3390/cancers16173108 - 8 Sep 2024
Viewed by 993
Abstract
Tumor cells produce excessive reactive oxygen species (ROS) but cannot detoxify ROS if they are due to an external agent. An agent that produces toxic levels of ROS, specifically in tumor cells, could be an effective anticancer drug. CMC-2 is a molecular hybrid [...] Read more.
Tumor cells produce excessive reactive oxygen species (ROS) but cannot detoxify ROS if they are due to an external agent. An agent that produces toxic levels of ROS, specifically in tumor cells, could be an effective anticancer drug. CMC-2 is a molecular hybrid of the bioactive polyphenol curcumin conjugated to dichloroacetate (DCA) via a glycine bridge. The CMC-2 was tested for its cytotoxic antitumor activities and killed both naïve and multidrug-resistant (MDR) bladder cancer (BCa) cells with equal potency (<1.0 µM); CMC-2 was about 10–15 folds more potent than curcumin or DCA. Growth of human BCa xenograft in mice was reduced by >50% by oral gavage of 50 mg/kg of CMC-2 without recognizable systemic toxicity. Doses that used curcumin or DCA showed minimum antitumor effects. In vitro, the toxicity of CMC-2 in both naïve and MDR cells depended on increased intracellular ROS in tumor cells but not in normal cells at comparable doses. Increased ROS caused the permeabilization of mitochondria and induced apoptosis. Further, adding N-Acetyl cysteine (NAC), a hydroxyl radical scavenger, abolished excessive ROS production and CMC-2’s cytotoxicity. The lack of systemic toxicity, equal potency against chemotherapy -naïve and resistant tumors, and oral bioavailability establish the potential of CMC-2 as a potent drug against bladder cancers. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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11 pages, 964 KiB  
Article
Evaluating Treatment Patterns and the Role of Neoadjuvant Chemotherapy in Plasmacytoid Urothelial Carcinoma: Insights from a Combined National and Institutional Series
by Syed Rahman, Victoria Kong, Michael Jalfon, David Hesse, Joseph Kim, Jonathan L. Wright, Adebowale Adeniran, Peter Humphrey, Darryl T. Martin and Fady Ghali
Cancers 2024, 16(17), 3050; https://doi.org/10.3390/cancers16173050 - 1 Sep 2024
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Abstract
Background: Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience. Methods: The NCDB was queried for localized [...] Read more.
Background: Plasmacytoid urothelial carcinoma (PUC) is a rare histologic subtype of urothelial carcinoma of the bladder (BC). Our objective was to characterize treatment patterns and outcomes of PUC in the NCDB and our recent institutional experience. Methods: The NCDB was queried for localized PUC cases between 2004 and 2020. Patients with PUC from a single institution (Yale School of Medicine) were also incorporated from 2021 onwards to not double-count patients. The primary outcomes were overall survival and treatment trends. Results: A total of 146 patients were included, 123 from NCDB and 23 from Yale. The median overall survival (mOS) was 28 [IQR 7.5, 50.3] months, 23 [IQR 8.4, 46.3] months for the NCDB patients, and 36 [IQR 4.3, 68.1] for the Yale patients. The mOS for patients receiving neoadjuvant chemotherapy (NAC) was 60.0 [28.0, 91.9] vs. 14.8 months [0, 34.3] for patients without NAC, p = 0.038, though the benefit was not preserved in a Cox proportional hazard analysis incorporating the clinical stage, receipt of NAC, and age. The peritoneum was the most common site of metastasis (78.3%), followed by the liver and bones. Conclusion: Our findings underscore the formidable challenge posed by PUC, emphasizing its limited response to current therapies. Despite higher pT0 rates with NAC, the OS benefit remains inconclusive, highlighting the need for more effective treatments. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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13 pages, 962 KiB  
Article
Global Trial Representation and Availability of Tyrosine Kinase Inhibitors for Treatment of Chronic Myeloid Leukemia
by Mycal Casey, Lorriane Odhiambo, Nidhi Aggarwal, Mahran Shoukier, K. M. Islam and Jorge Cortes
Cancers 2024, 16(16), 2838; https://doi.org/10.3390/cancers16162838 - 14 Aug 2024
Viewed by 1252
Abstract
Background: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). Methods: CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999–2019) from the Institute of Health Metrics and [...] Read more.
Background: Evaluating clinical trial representation for countries with different socio-demographic index (SDI) and tyrosine kinase inhibitor (TKI) availability for chronic myeloid leukemia (CML). Methods: CML incidence rates (IRs) and disability-adjusted life years (DALYs) (1999–2019) from the Institute of Health Metrics and Evaluation were analyzed. Trials investigating TKI use in CML were obtained from ClinicalTrials.gov. Site data for eligible trials (N = 30) and DALYs were analyzed. TKI approvals, DALYs, and IRs were summarized by SDI. Results: North America (NA) had significant decreases in annual percent change (APC) in DALYs and incidence rates from 1999 to 2004. IRs were highest in Europe and Central Asia (ECA) and NA, while DALYs were highest in South Asia (SAsia) and Sub-Saharan Africa (SSA). Countries in the high-SDI quintile were likely to have lower DALYs than lower-SDI quintiles. Differences in regional DALYs vs. sites in TKI trials were significant for SAsia, SSA, and ECA. High-SDI countries were included in all 30 trials, and TKI approvals were prominent in high-SDI (142) vs. low-SDI (14) countries. Conclusions: The inclusion of disproportionately affected countries during the design of and recruitment into clinical trials should occur, as should TKI availability. The lack of representation demonstrates healthcare disparities. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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13 pages, 749 KiB  
Article
Adverse Events in Anti-PD-1-Treated Adjuvant and First-Line Advanced Melanoma Patients
by Daan Jan Willem Rauwerdink, Olivier van Not, Melissa de Meza, Remco van Doorn, Jos van der Hage, A. J. M. van den Eertwegh, John B. Haanen, Maureen J. B. Aarts, Franchette W. P. J. van den Berkmortel, Christiaan U. Blank, Marye J. Boers-Sonderen, Jan Willem B. de Groot, Geke A. P. Hospers, Djura Piersma, Rozemarijn S. van Rijn, A. M. Stevense-den Boer, Astrid A. M. van der Veldt, Gerard Vreugdenhil, Michel W. J. M. Wouters, Karijn P. M. Suijkerbuijk and Ellen Kapiteijnadd Show full author list remove Hide full author list
Cancers 2024, 16(15), 2656; https://doi.org/10.3390/cancers16152656 - 26 Jul 2024
Viewed by 976
Abstract
Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 [...] Read more.
Introduction: The difference in incidence and severity of anti-PD-1 therapy-related adverse events (irAEs) between adjuvant and advanced treated melanoma patients remains unclear, as no head-to-head studies have compared these groups. Methods: This multi-center cohort study analyzed melanoma patients treated with anti-PD-1 in adjuvant or advanced settings between 2015 and 2021. Comorbidities and ECOG performance status were assessed before treatment, and grade III-IV irAEs were monitored during treatment. Univariate and multivariate regression analyses were conducted to identify factors associated with irAE development. Results: A total of 1465 advanced melanoma patients and 908 resected melanoma patients received anti-PD-1 therapy. Adjuvant-treated patients were younger, with a median age of 63 years compared to 69 years in the advanced group (p < 0.01), and had a better ECOG performance status (p < 0.01). Comorbidities were seen more frequently in advanced melanoma patients than in those receiving adjuvant treatment, 76% versus 68% (p < 0.01). Grade III-IV irAEs occurred in 214 (15%) advanced treated patients and in 119 (13%) adjuvant-treated patients. Multivariate analysis showed an increased risk of severe irAE development with the presence of any comorbidity (adjusted OR 1.22, 95% CI 1.02–1.44) and ECOG status greater than 1 (adjusted OR 2.00, 95% CI 1.20–3.32). Adjuvant therapy was not associated with an increased risk of irAE development compared to advanced treatment (adjusted OR 0.95, 95% CI 0.74–1.21) after correcting for comorbidities and ECOG performance score. Anti-PD-1 therapy was halted due to toxicity (any grade irAE) more often in the adjuvant setting than in the advanced setting, 20% versus 15% (p < 0.01). Conclusions: Higher ECOG performance status and presence of any comorbidity were independently associated with an increased risk of Grade III-IV irAE in adjuvant and advanced treated melanoma patients. Patients treated in the adjuvant setting did not have an increased risk of developing severe irAEs compared to advanced melanoma patients. These findings are of clinical significance in consulting patients for adjuvant anti-PD-1 treatment. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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Review

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19 pages, 2092 KiB  
Review
Histology Agnostic Drug Development: An Updated Review
by Kevin Nguyen, Karina Fama, Guadalupe Mercado, Yin Myat and Kyaw Thein
Cancers 2024, 16(21), 3642; https://doi.org/10.3390/cancers16213642 - 29 Oct 2024
Viewed by 396
Abstract
Recent advancements in oncology have led to the development of histology-agnostic therapies, which target genetic alterations irrespective of the tumor’s tissue of origin. This review aimed to provide a comprehensive update on the current state of histology-agnostic drug development, focusing on key therapies, [...] Read more.
Recent advancements in oncology have led to the development of histology-agnostic therapies, which target genetic alterations irrespective of the tumor’s tissue of origin. This review aimed to provide a comprehensive update on the current state of histology-agnostic drug development, focusing on key therapies, including pembrolizumab, larotrectinib, entrectinib, dostarlimab, dabrafenib plus trametinib, selpercatinib, trastuzumab deruxtecan, and reprotrectinib. We performed a detailed analysis of each therapy’s mechanism of action, clinical trial outcomes, and associated biomarkers. The review further explores challenges in drug resistance, such as adaptive signaling pathways and neoantigen variability, as well as diagnostic limitations in identifying optimal patient populations. While these therapies have demonstrated efficacy in various malignancies, significant hurdles remain, including intratumoral heterogeneity and resistance mechanisms that diminish treatment effectiveness. We propose considerations for refining trial designs and emerging biomarkers, such as tumor neoantigen burden, to enhance patient selection. These findings illustrate the transformative potential of histology-agnostic therapies in precision oncology but highlight the need for continued research to optimize their use and overcome existing barriers. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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38 pages, 6103 KiB  
Review
Blood–Brain Barrier Conquest in Glioblastoma Nanomedicine: Strategies, Clinical Advances, and Emerging Challenges
by Mengyun Duan, Ruina Cao, Yuan Yang, Xiaoguang Chen, Lian Liu, Boxu Ren, Lingzhi Wang and Boon-Cher Goh
Cancers 2024, 16(19), 3300; https://doi.org/10.3390/cancers16193300 - 27 Sep 2024
Viewed by 1220
Abstract
Glioblastoma (GBM) is a prevalent type of malignancy within the central nervous system (CNS) that is associated with a poor prognosis. The standard treatment for GBM includes the surgical resection of the tumor, followed by radiotherapy and chemotherapy; yet, despite these interventions, overall [...] Read more.
Glioblastoma (GBM) is a prevalent type of malignancy within the central nervous system (CNS) that is associated with a poor prognosis. The standard treatment for GBM includes the surgical resection of the tumor, followed by radiotherapy and chemotherapy; yet, despite these interventions, overall treatment outcomes remain suboptimal. The blood–brain barrier (BBB), which plays a crucial role in maintaining the stability of brain tissue under normal physiological conditions of the CNS, also poses a significant obstacle to the effective delivery of therapeutic agents to GBMs. Recent preclinical studies have demonstrated that nanomedicine delivery systems (NDDSs) offer promising results, demonstrating both effective GBM targeting and safety, thereby presenting a potential solution for targeted drug delivery. In this review, we first explore the various strategies employed in preclinical studies to overcome the BBB for drug delivery. Subsequently, the results of the clinical translation of NDDSs are summarized, highlighting the progress made. Finally, we discuss potential strategies for advancing the development of NDDSs and accelerating their translational research through well-designed clinical trials in GBM therapy. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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19 pages, 562 KiB  
Review
CAR-T Cells in the Treatment of Nervous System Tumors
by Ugo Testa, Germana Castelli and Elvira Pelosi
Cancers 2024, 16(16), 2913; https://doi.org/10.3390/cancers16162913 - 22 Aug 2024
Viewed by 1011
Abstract
Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy has been particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various [...] Read more.
Chimeric antigen receptor T cells (CAR-Ts) have shown a remarkable efficacy in hematological malignancies but limited responses in solid tumors. Among solid tumors, CAR-T cell therapy has been particularly explored in brain tumors. CAR-T cells have shown a limited clinical efficacy in various types of brain tumors due to several factors that have hampered their activity, including tumor antigen heterogeneity, the limited access of CAR-T cells to brain tumor cells, limited CAR-T cell trafficking and in vivo persistence and the presence of a highly immunosuppressive tumor microenvironment. Despite these considerations, some recent studies have shown promising antitumor activity of GD2-CAR-T cells on diffuse midline gliomas and neuroblastomas and of CARv3-TEAM-E cells in glioblastomas. However, strategies are required to improve the effect of CAR-T cells in brain tumors, including advanced CAR-T cell design with multiple antigenic targeting and incorporation of combination therapies. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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22 pages, 2714 KiB  
Review
Cholangiocarcinoma: The Current Status of Surgical Options including Liver Transplantation
by Abdullah Esmail, Mohamed Badheeb, Batool Alnahar, Bushray Almiqlash, Yara Sakr, Bayan Khasawneh, Ebtesam Al-Najjar, Hadeel Al-Rawi, Ala Abudayyeh, Yaser Rayyan and Maen Abdelrahim
Cancers 2024, 16(11), 1946; https://doi.org/10.3390/cancers16111946 - 21 May 2024
Cited by 4 | Viewed by 1881
Abstract
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor [...] Read more.
Cholangiocarcinoma (CCA) poses a substantial threat as it ranks as the second most prevalent primary liver tumor. The documented annual rise in intrahepatic CCA (iCCA) incidence in the United States is concerning, indicating its growing impact. Moreover, the five-year survival rate after tumor resection is only 25%, given that tumor recurrence is the leading cause of death in 53–79% of patients. Pre-operative assessments for iCCA focus on pinpointing tumor location, biliary tract involvement, vascular encasements, and metastasis detection. Numerous studies have revealed that portal vein embolization (PVE) is linked to enhanced survival rates, improved liver synthetic functions, and decreased overall mortality. The challenge in achieving clear resection margins contributes to the notable recurrence rate of iCCA, affecting approximately two-thirds of cases within one year, and results in a median survival of less than 12 months for recurrent cases. Nearly 50% of patients initially considered eligible for surgical resection in iCCA cases are ultimately deemed ineligible during surgical exploration. Therefore, staging laparoscopy has been proposed to reduce unnecessary laparotomy. Eligibility for orthotopic liver transplantation (OLT) requires certain criteria to be granted. OLT offers survival advantages for early-detected unresectable iCCA; it can be combined with other treatments, such as radiofrequency ablation and transarterial chemoembolization, in specific cases. We aim to comprehensively describe the surgical strategies available for treating CCA, including the preoperative measures and interventions, alongside the current options regarding liver resection and OLT. Full article
(This article belongs to the Special Issue Feature Paper in Section “Cancer Therapy” in 2024)
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