Cancer treatment reviews最新文献

{"title":"Current status and future prospects of combined immunotherapy and epidermal growth factor receptor inhibitors in head and neck squamous cell carcinoma","authors":"Xin Tian ,&nbsp;Hongyan Zhang ,&nbsp;Yiman Han ,&nbsp;Baoru Gu ,&nbsp;Zhenyong Zhang","doi":"10.1016/j.ctrv.2024.102864","DOIUrl":"10.1016/j.ctrv.2024.102864","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is a malignancy with a poor prognosis, and the majority of patients with HNSCC are diagnosed at later stages owing to its hidden anatomical location and atypical clinical symptoms. It is notably prone to recurrence and metastasis. The traditional treatments include surgery, radiotherapy, chemotherapy, and targeted therapy. Although multiple treatment strategies have been established, the prognosis remains poor because most patients develop resistance to traditional treatments. In recent years, epidermal growth factor receptor (EGFR) inhibitors and immune checkpoint inhibitors (ICIs) have been shown to provide clinical benefits to these patients. Based on the promising results of both anti-EGFR therapy and immunotherapy, as well as the biological rationale for combining immunotherapy with anti-EGFR drugs, numerous preclinical and ongoing or completed clinical trials have explored the use of their synergistic effects. This review summarizes the feasibility of combining immunotherapy with EGFR inhibitors for HNSCC treatment and analyses the relevant biomarkers. It also summarizes the strategies for clinical applications. We found that immunotherapy and EGFR inhibitor combination therapy showed promise in treating patients with HNSCC and exhibited safety with acceptable adverse events. This review may provide valuable insights for the future development of treatments and formulation of therapeutic strategies for HNSCC, as well as useful information for the future design of clinical trials.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102864"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PI3K/AKT/mTOR inhibitors for hormone receptor-positive advanced breast cancer","authors":"Chunfang Hao ,&nbsp;Yunchu Wei ,&nbsp;Wenjing Meng ,&nbsp;Jie Zhang ,&nbsp;Xiaonan Yang","doi":"10.1016/j.ctrv.2024.102861","DOIUrl":"10.1016/j.ctrv.2024.102861","url":null,"abstract":"<div><div>Dysregulation of the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway plays a pivotal role in the development and progression of various cancers. In hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer, aberrations in this pathway are increasingly recognized as key drivers of resistance to endocrine therapy and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors, the first-line treatments for this disease subtype. Recognizing the urgent need for alternative therapeutic strategies, significant advancements have been made in developing PI3K/AKT/mTOR inhibitors for HR+ advanced/metastatic breast cancer. Among these inhibitors, capivasertib and alpelisib have received approval as targeted therapies for this indication. This review provides a comprehensive summary of the latest developments in PI3K/AKT/mTOR inhibitors for HR+ breast cancer. It also delves into different aspects, including sampling, testing method and timing, of PI3K/AKT/mTOR diagnostic testing. Additionally, the review discusses key considerations for integrating these inhibitors into clinical practice, such as timing and choice of PI3K/AKT/mTOR inhibitors, and management of treatment toxicities. By examining these different aspects, this review aims to provide valuable insights into optimizing the clinical utility of PI3K/AKT/mTOR inhibitors in HR+ advanced breast cancer.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102861"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and safety of antibody-drug conjugates in pretreated HER2-low metastatic breast cancer: A systematic review and network meta-analysis","authors":"Francesco Schettini ,&nbsp;Sabrina Nucera ,&nbsp;Tomás Pascual ,&nbsp;Olga Martínez-Sáez ,&nbsp;Rodrigo Sánchez-Bayona ,&nbsp;Benedetta Conte ,&nbsp;Giuseppe Buono ,&nbsp;Matteo Lambertini ,&nbsp;Kevin Punie ,&nbsp;Juan Miguel Cejalvo ,&nbsp;Grazia Arpino ,&nbsp;Paolo Vigneri ,&nbsp;Daniele Generali ,&nbsp;Eva Ciruelos ,&nbsp;Javier Cortés ,&nbsp;Alessandra Gennari ,&nbsp;Montserrat Muñoz ,&nbsp;Maria J. Vidal Losada ,&nbsp;Sara M Tolaney ,&nbsp;Aleix Prat ,&nbsp;Guillermo Villacampa","doi":"10.1016/j.ctrv.2024.102865","DOIUrl":"10.1016/j.ctrv.2024.102865","url":null,"abstract":"<div><h3>Introduction</h3><div>Antibody-drug conjugates (ADCs) trastuzumab-deruxtecan (T-DXd) and sacituzumab-govitecan (SG) provided significant progression-free survival (PFS) and overall survival (OS) improvements over chemotherapy (CT) in pretreated hormone receptor-positive (HR+) and triple-negative (TN)/HER2-low metastatic breast cancer (MBC). However, no direct comparison between the two exists, nor with the more recent datopotamab-deruxtecan (Dato-DXd).</div></div><div><h3>Methods</h3><div>We conducted a network meta-analysis (NMA) to compare efficacy and safety of T-DXd and SG in CT-pretreated HR+ and TN/HER2-low MBC and assess their benefit over standard CT, exploring also a comparison with Dato-DXd. Hazard ratios (HRs) with 95 % confidence intervals (CI) were calculated for PFS/OS. P-score was used for treatment ranking.</div></div><div><h3>Results</h3><div>Three RCTs (956 patients) were included in the primary analysis and 5 (1,445) in the exploratory NMA with Dato-DXd. In HR+/HER2-low, T-DXd showed no significant difference in PFS and OS when compared to SG. Similarly, in TN/HER2-low, PFS and OS did not differ significantly between the two ADCs. The P-score analysis favored T-DXd over SG in HR+/HER2-low in PFS (0.90 vs. 0.60) and OS (0.89 vs. 0.60). SG was favored over T-DXd in OS in TN/HER2-low (0.80 vs. 0.69). Similar results were obtained for HR+ MBC when including Dato-Dxd, which showed the worst performance, while T-DXd was the only ADC significantly outperforming CT in OS. The ADCs showed significantly better PFS and OS than CT in HR+/HER2-low and TN/HER2-low (all p &lt; 0.001). SG had higher rates of neutropenia, diarrhea and alopecia vs. T-DXd, which showed more thrombocytopenia, fatigue and nausea. Pneumonitis and cardiotoxicity were typically T-DXd-related, and T-DXd showed more toxicity-related discontinuations.</div></div><div><h3>Conclusions</h3><div>Similar efficacy with T-DXd and SG in HER2-low MBC was observed, regardless of HR status. Safety profile, local drug-approval criteria and guidelines, patients’ preferences and overall quality of evidence should ultimately guide therapeutic decision-making. Dato-DXd role remains uncertain.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102865"},"PeriodicalIF":9.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142878697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Practical clinical management of ocular adverse events related to Antibody-Drug Conjugates in gynaecological malignancies","authors":"Bochra Bouguerra Zina ,&nbsp;Frédérique Rousseau ,&nbsp;Stephan Fauquier ,&nbsp;Renaud Sabatier ,&nbsp;Maria Kfoury","doi":"10.1016/j.ctrv.2024.102867","DOIUrl":"10.1016/j.ctrv.2024.102867","url":null,"abstract":"<div><h3>Background</h3><div>The advent of Antibody-Drug Conjugates (ADC) represents a significant advancement in targeted therapy for gynaecological malignancies. However, the ocular toxicities associated with ADCs, particularly Tisotumab Vedotin (TV) and Mirvetuximab Soravtansine (MIRV) necessitate effective mitigation in order to optimise patient care.</div></div><div><h3>Methods</h3><div>This review synthesises findings from clinical trials to delineate the spectrum of ocular adverse events induced by ADCs. The analysis focuses on the incidence, onset, severity and reversibility of adverse events. It examines the underlying mechanisms of toxicity and provides management strategies based on study protocols.</div></div><div><h3>Results</h3><div>Adverse events mainly impact the anterior ocular segment, resulting in conjunctivitis and keratopathy. They affect up to 56 % of patients treated with MIRV and 50 to 60 % of those receiving TV. Symptoms like blurred vision, dryness and pain hinder the patient’s quality of life. Events are CTCAE grade 3 or higher in less than 10 % of cases. The median time to onset is 1.3 months. However, ocular toxicity may appear up to 10 months after treatment initiation, indicating a need for prolonged vigilance. Primary prophylaxis calls for local corticotherapy, lubricants and in some cases, vasoconstrictors. Despite the potential for severity, most cases are reversible with local treatment and transient dose reduction and/or delay. Close monitoring is crucial for early detection and subsequent management.</div></div><div><h3>Conclusions</h3><div>Clinicians ought to be cognizant of the potential ocular toxicity of ADCs. Proactive prophylaxis, patient education and a multidisciplinary approach involving ophthalmologists are paramount to minimising the impact of these AEs. Further research is essential to measure the real outcome of preventive strategies and balance their benefits with potential short and long-term risks.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"134 ","pages":"Article 102867"},"PeriodicalIF":9.6,"publicationDate":"2024-12-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436698","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert consensus on the prevention of brain metastases in patients with HER2-positive breast cancer","authors":"Volkmar Müller ,&nbsp;Thomas Bachelot ,&nbsp;Giuseppe Curigliano ,&nbsp;Evandro de Azambuja ,&nbsp;Julia Furtner ,&nbsp;Jens Gempt ,&nbsp;Barbara Alicja Jereczek-Fossa ,&nbsp;Katarzyna J. Jerzak ,&nbsp;Emilie Le Rhun ,&nbsp;Carlo Palmieri ,&nbsp;Gabriella Pravettoni ,&nbsp;Cristina Saura ,&nbsp;Rupert Bartsch","doi":"10.1016/j.ctrv.2024.102860","DOIUrl":"10.1016/j.ctrv.2024.102860","url":null,"abstract":"<div><h3>Background</h3><div>Patients with HER2-positive breast cancer have a significant risk of developing brain metastases (BrM), which have detrimental effects on survival outcomes and quality of life. Although there are several systemic treatment options available that may delay the appearance of BrM and secondary progression of previously treated BrM, there are still substantial unmet needs for this patient population and primary prevention remains elusive.</div></div><div><h3>Methods</h3><div>A group of experts created consensus statements, through a modified Delphi process, to bridge the gap between current unmet needs, available evidence, and international guidelines.</div></div><div><h3>Results</h3><div>The steering committee reviewed all relevant literature and formed research questions to be answered by the subsequent consensus statements. In total, 61 contributors provided feedback on the consensus statements, with 34 statements reaching agreement out of the 55 statements that were voted on altogether. Statements with consensus aimed to define BrM primary and secondary prevention, screening procedures, assessment of symptoms, treatment efficacy, and preventing the occurrence and progression of BrM, while acknowledging the possibilities and limitations in daily clinical practice. Some statements did not reach agreement for a variety of reasons, mostly due to lack of evidence.</div></div><div><h3>Conclusions</h3><div>The consensus statements outlined in this publication provide a point of reference for daily clinical practice and can act as recommendations for clinical trial procedures and future guidelines.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102860"},"PeriodicalIF":9.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142746879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer","authors":"Rupert Bartsch ,&nbsp;David Cameron ,&nbsp;Eva Ciruelos ,&nbsp;Carmen Criscitiello ,&nbsp;Giuseppe Curigliano ,&nbsp;Francois P Duhoux ,&nbsp;Theodoros Foukakis ,&nbsp;Joseph Gligorov ,&nbsp;Nadia Harbeck ,&nbsp;Nathalie LeVasseur ,&nbsp;Alicia Okines ,&nbsp;Frederique Penault-Llorca ,&nbsp;Volkmar Müller","doi":"10.1016/j.ctrv.2024.102853","DOIUrl":"10.1016/j.ctrv.2024.102853","url":null,"abstract":"<div><div>Human epidermal growth factor receptor 2 (HER2) overexpression and/or <em>ERBB2</em> gene amplification occurs in approximately 15–20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer. However, in the third-line treatment setting and beyond, there is a lack of clarity of the preferred choice of therapy. In clinical practice, clinicians may also encounter challenging scenarios where the optimal therapeutic approach has not been defined by clinical studies, so there is a need for clarity in such situations. Two consensus meetings of expert oncologists (12 from Europe and one from Canada) were convened to discuss these scenarios. We subsequently developed this article to present an overview of current treatment recommendations for HER2-positive metastatic breast cancer and give practical guidance on addressing challenging scenarios in a real-world setting. Based on our clinical experience, we provide a unanimous consensus concerning the treatment of elderly patients as well as those with brain-only metastases, leptomeningeal disease, oligometastatic disease, central nervous system oligo-progressive disease or <em>ERBB2</em>-mutant disease. We also discuss how to combine HER2-targeted therapy with endocrine therapy in patients with HER2-positive/hormone-receptor-positive disease, considerations for potential discontinuation of HER2-targeted therapy in patients with long-term remission and how to treat patients whose metastatic biopsy no longer confirms their HER2-positive status.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102853"},"PeriodicalIF":9.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142706260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen Signaling in Early-Stage Breast Cancer: Impact on Neoadjuvant Chemotherapy and Immunotherapy","authors":"Chiara Corti ,&nbsp;Busem Binboğa Kurt ,&nbsp;Beyza Koca ,&nbsp;Tasnim Rahman ,&nbsp;Fabio Conforti ,&nbsp;Laura Pala ,&nbsp;Giampaolo Bianchini ,&nbsp;Carmen Criscitiello ,&nbsp;Giuseppe Curigliano ,&nbsp;Ana C. Garrido-Castro ,&nbsp;Sheheryar K. Kabraji ,&nbsp;Adrienne G. Waks ,&nbsp;Elizabeth A. Mittendorf ,&nbsp;Sara M. Tolaney","doi":"10.1016/j.ctrv.2024.102852","DOIUrl":"10.1016/j.ctrv.2024.102852","url":null,"abstract":"<div><div>Neoadjuvant chemoimmunotherapy (NACIT) has been shown to improve pathologic complete response (pCR) rates and survival outcomes in stage II-III triple-negative breast cancer (TNBC). Promising pCR rate improvements have also been documented for selected patients with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC). However, one size does not fit all and predicting which patients will benefit from NACIT remains challenging. Accurate predictions would be useful to minimize immune-related toxicity, which can be severe, irreversible, and potentially impact fertility and quality of life, and to identify patients in need of alternative treatments.</div><div>This review aims to capitalize on the existing translational and clinical evidence on predictors of treatment response in patients with early-stage BC treated with neoadjuvant chemotherapy (NACT) and NACIT. It summarizes evidence suggesting that NACT/NACIT effectiveness may correlate with pre-treatment tumor characteristics, including mutational profiles, ER expression and signaling, immune cell presence and spatial organization, specific gene signatures, and the levels of proliferating versus quiescent cancer cells.</div><div>However, the predominantly qualitative and descriptive nature of many studies highlights the challenges in integrating various potential response determinants into a validated, comprehensive, and multimodal predictive model. The potential of novel multi-modal approaches, such as those based on artificial intelligence, to overcome current challenges remains unclear, as these tools are not free from bias and shortcut learning. Despite these limitations, the rapid evolution of these technologies, coupled with further efforts in basic and translational research, holds promise for improving treatment outcome predictions in early HER2- BC.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"132 ","pages":"Article 102852"},"PeriodicalIF":9.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PARP inhibitors in gliomas: Mechanisms of action, current trends and future perspectives","authors":"Eugenia Cella ,&nbsp;Alberto Bosio ,&nbsp;Pasquale Persico ,&nbsp;Mario Caccese ,&nbsp;Marta Padovan ,&nbsp;Agnese Losurdo ,&nbsp;Marta Maccari ,&nbsp;Giulia Cerretti ,&nbsp;Tamara Ius ,&nbsp;Giuseppe Minniti ,&nbsp;Ahmed Idbaih ,&nbsp;Nader Sanai ,&nbsp;Michael Weller ,&nbsp;Matthias Preusser ,&nbsp;Matteo Simonelli ,&nbsp;Giuseppe Lombardi","doi":"10.1016/j.ctrv.2024.102850","DOIUrl":"10.1016/j.ctrv.2024.102850","url":null,"abstract":"<div><div>Gliomas are the most common primary malignant brain tumours in adults. Despite decades of research into novel therapeutic approaches, the prognosis remains poor. PARP1-2 are critical for DNA repair, cell survival and genomic stability and PARP inhibition (PARPi) may be a promising therapeutic approach for gliomas. Inhibition of PARP activity leads to homologous recombination deficiency (HRD), which, in combination with DNA damage, results in cell death. This review summarises the current knowledge and future perspectives of PARPi in glioma. The available literature was reviewed using PubMed, recent major international oncology congresses were consulted, and ongoing clinical trials were searched using <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>.</div><div>In translational research, PARPi have demonstrated a strong scientific rationale for their use in the treatment of glioma. They have been evaluated both alone and in combination with radiotherapy, temozolomide, anti-angiogenic agents, immunotherapy and other new drugs in newly diagnosed or recurrent glioma. Most studies were open-label, non-randomised, dose-escalation phase I-II trials. Early results show promising anti-tumour activity, and key challenges include identifying predictive biomarkers, elucidating synergistic effects in combination therapies, addressing the development of resistance, and managing hematological toxicity.</div><div>In conclusion, early phase studies have shown promising anti-tumour activity of PARPi that should be confirmed in larger prospective and randomised trials. In addition, the development of novel PARPi with improved blood brain barrier (BBB) penetration and PARP inhibitor activity with new synergistic treatment combinations seems promising and needs to be further explored.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102850"},"PeriodicalIF":9.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634548","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Optimizing outcomes and personalizing care with targeted agents in advanced cholangiocarcinoma","authors":"Umair Mahmood ,&nbsp;Ahmed Abbass ,&nbsp;Khurum Khan","doi":"10.1016/j.ctrv.2024.102851","DOIUrl":"10.1016/j.ctrv.2024.102851","url":null,"abstract":"<div><div>Traditional chemotherapy and immunotherapy-based systemic treatments for locally advanced or metastatic cholangiocarcinoma have been associated with poor clinical outcomes driven partly by molecular heterogeneity promoting early treatment resistance and a higher toxicity profile associated with these regimens. Few patients are eligible for upfront surgical resection and clinical studies have been traditionally difficult to conduct due to the orphan nature of this disease. However, increasing use of genomic profiling in clinical practice have led to active investigations of aberrant albeit promising mechanistic therapeutic targets such as <em>IDH-1, FGFRs, BRAF^V600E, HER-2</em> and <em>NTRK</em>.</div><div>This review article aims to highlight the complex genomic landscape of this difficult-to-treat disease, followed by a discussion of evidence-based biological mechanisms that can be actioned using targeted agents. We explore the clinical rationale behind a targeted therapeutic strategy, the role of liquid biopsies in guiding clinical decisions and future treatment pathways for cholangiocarcinoma management. We also discuss the challenges and opportunities originating from recent clinical trials evaluating targeted treatments and our own institutional experience at UCLH that have aimed to address some of these biological complexities and have translated into improved patient outcomes via effective molecularly driven patient selection strategies. We also provide perspectives on emerging novel, next generation targeted inhibitors overcoming treatment resistance to previous targeted agents with demonstrated clinical value in a challenging patient population.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102851"},"PeriodicalIF":9.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607699","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Local administration of immunotherapy for patients with skin cancer: A systematic review","authors":"J.C. Janssen ,&nbsp;B. van Dijk ,&nbsp;L.L. Hoeijmakers ,&nbsp;D.J. Grünhagen ,&nbsp;W.M. Bramer ,&nbsp;C. Verhoef ,&nbsp;T.D. de Gruijl ,&nbsp;C.U. Blank ,&nbsp;A.A.M. van der Veldt","doi":"10.1016/j.ctrv.2024.102848","DOIUrl":"10.1016/j.ctrv.2024.102848","url":null,"abstract":"<div><div>Since the introduction of immune checkpoint inhibitors (ICIs) targeting PD-1 and CTLA-4 receptors, survival has improved significantly for patients with irresectable and metastatic skin cancer, including cutaneous squamous cell cancer and melanoma. However, systemic administration of these drugs is associated with immune related adverse events (irAEs), which can be severe, irreversible and even fatal. To reduce the risk of irAEs associated with systemic exposure to immunotherapeutic drugs, local administration of low doses could be considered. This systematic review provides an overview of early phase clinical trials with drugs that are currently under investigation for intratumoral administration in patients with melanoma and non-melanoma skin cancer.</div></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":"131 ","pages":"Article 102848"},"PeriodicalIF":9.6,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142561129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}