Pub Date : 2024-06-03DOI: 10.1016/j.ctrv.2024.102774
Qi Zhang , Xiaoli Zhang , Peipei Xie , Wen Zhang
Cancer has become the second leading cause of death in the world, and more than 50% of cancer patients are diagnosed at an advanced stage. Early diagnosis of tumours is the key to improving patient quality of life and survival time and reducing the socioeconomic burden. However, there is still a lack of reliable early diagnosis methods in clinical practice. In recent years, liquid biopsy technology has developed rapidly. It has the advantages of noninvasiveness, easy access to sample sources, and reproducibility. It has become the main focus of research on the early diagnosis methods of tumours. This review summarises the research progress of existing liquid biopsy markers, such as circulating tumour DNA, circulating viral DNA, DNA methylation, circulating tumour cells, circulating RNA, exosomes, and tumour education platelets in early diagnosis of tumours, and analyses the current advantages and limitations of various markers, providing a direction for the application and transformation of liquid biopsy research in early diagnosis of clinical tumours.
{"title":"Liquid biopsy: An arsenal for tumour screening and early diagnosis","authors":"Qi Zhang , Xiaoli Zhang , Peipei Xie , Wen Zhang","doi":"10.1016/j.ctrv.2024.102774","DOIUrl":"10.1016/j.ctrv.2024.102774","url":null,"abstract":"<div><p>Cancer has become the second leading cause of death in the world, and more than 50% of cancer patients are diagnosed at an advanced stage. Early diagnosis of tumours is the key to improving patient quality of life and survival time and reducing the socioeconomic burden. However, there is still a lack of reliable early diagnosis methods in clinical practice. In recent years, liquid biopsy technology has developed rapidly. It has the advantages of noninvasiveness, easy access to sample sources, and reproducibility. It has become the main focus of research on the early diagnosis methods of tumours. This review summarises the research progress of existing liquid biopsy markers, such as circulating tumour DNA, circulating viral DNA, DNA methylation, circulating tumour cells, circulating RNA, exosomes, and tumour education platelets in early diagnosis of tumours, and analyses the current advantages and limitations of various markers, providing a direction for the application and transformation of liquid biopsy research in early diagnosis of clinical tumours.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141280862","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}
Pub Date : 2024-06-01DOI: 10.1016/j.ctrv.2024.102773
Ben O’Leary , Heath Skinner , Jonathan D Schoenfeld , Lisa Licitra , Christophe Le Tourneau , Christina Esdar , Andreas Schroeder , Satu Salmio , Amanda Psyrri
Combinations of surgery, radiotherapy and chemotherapy can eradicate tumors in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), but a significant proportion of tumors progress, recur, or do not respond to therapy due to treatment resistance. The prognosis for these patients is poor, thus new approaches are needed to improve outcomes. Key resistance mechanisms to chemoradiotherapy (CRT) in patients with LA SCCHN are alterations to the pathways that mediate apoptosis, a form of programmed cell death. Targeting dysregulation of apoptotic pathways represents a rational therapeutic strategy in many types of cancer, with a number of proteins, including the pro-survival B-cell lymphoma 2 family and inhibitors of apoptosis proteins (IAPs), having been identified as druggable targets. This review discusses the mechanisms by which apoptosis occurs under physiological conditions, and how this process is abnormally restrained in LA SCCHN tumor cells, with treatment strategies aimed at re-enabling apoptosis in LA SCCHN also considered. In particular, the development of, and future opportunities for, IAP inhibitors in LA SCCHN are discussed, in light of recent encouraging proof-of-concept clinical trial data.
对于局部晚期头颈部鳞状细胞癌(LA SCCHN)患者,手术、放疗和化疗的组合疗法可以根除肿瘤,但相当一部分肿瘤会进展、复发或因耐药性而对治疗无效。这些患者的预后很差,因此需要新的方法来改善预后。LA SCCHN患者对化疗放疗(CRT)的主要耐药机制是介导细胞凋亡(一种程序性细胞死亡)的通路发生了改变。针对凋亡通路的失调是许多类型癌症的合理治疗策略,包括促生存B细胞淋巴瘤2家族和凋亡蛋白抑制剂(IAPs)在内的许多蛋白已被确定为药物靶点。本综述讨论了凋亡在生理条件下发生的机制,以及这一过程如何在 LA SCCHN 肿瘤细胞中受到异常抑制,并探讨了旨在重新激活 LA SCCHN 细胞凋亡的治疗策略。特别是,根据最近令人鼓舞的概念验证临床试验数据,讨论了IAP抑制剂在LA SCCHN中的发展和未来机遇。
{"title":"Evasion of apoptosis and treatment resistance in squamous cell carcinoma of the head and neck","authors":"Ben O’Leary , Heath Skinner , Jonathan D Schoenfeld , Lisa Licitra , Christophe Le Tourneau , Christina Esdar , Andreas Schroeder , Satu Salmio , Amanda Psyrri","doi":"10.1016/j.ctrv.2024.102773","DOIUrl":"10.1016/j.ctrv.2024.102773","url":null,"abstract":"<div><p>Combinations of surgery, radiotherapy and chemotherapy can eradicate tumors in patients with locally advanced squamous cell carcinoma of the head and neck (LA SCCHN), but a significant proportion of tumors progress, recur, or do not respond to therapy due to treatment resistance. The prognosis for these patients is poor, thus new approaches are needed to improve outcomes. Key resistance mechanisms to chemoradiotherapy (CRT) in patients with LA SCCHN are alterations to the pathways that mediate apoptosis, a form of programmed cell death. Targeting dysregulation of apoptotic pathways represents a rational therapeutic strategy in many types of cancer, with a number of proteins, including the pro-survival B-cell lymphoma 2 family and inhibitors of apoptosis proteins (IAPs), having been identified as druggable targets. This review discusses the mechanisms by which apoptosis occurs under physiological conditions, and how this process is abnormally restrained in LA SCCHN tumor cells, with treatment strategies aimed at re-enabling apoptosis in LA SCCHN also considered. In particular, the development of, and future opportunities for, IAP inhibitors in LA SCCHN are discussed, in light of recent encouraging proof-of-concept clinical trial data.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141279188","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}
Pub Date : 2024-05-26DOI: 10.1016/j.ctrv.2024.102772
Pablo Jiménez-Labaig , Antonio Rullan , Alberto Hernando-Calvo , Sandra Llop , Shreerang Bhide , Ben O’Leary , Irene Braña , Kevin J. Harrington
Introduction
There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent unresectable and metastatic (R/M) setting. Antibody-drug conjugates (ADC) and bispecific antibodies (BsAb) may deliver promising results.
Methods
We conducted a systematic literature review to identify ADC and BsAb clinical trials, involving patients with HNSCC and NPC, from database creation to December 2023. We reported trial characteristics, overall response rate (ORR), overall survival (OS), and grade ≥ 3 treatment-related adverse events (trAEs).
Results
23 trials (65 % phase I) were found, involving 540 R/M patients (355 [20trials] HNSCC and 185 [5trials] NPC). There were 13 ADC (n = 343) and 10 BsAb (n = 197) trials. 96 % patients were refractory to standard of care treatments. ORR ranged from 0 to 100 %, with the highest ORR for GEN1042 plus chemoimmunotherapy. ORRs for monotherapies were 47 % for ADC, and 0–37 % for BsAb. MRG003 reached in HNSCC 43 % and NPC 47 %. BL-B01D1 54 % in NPC. Longest median OS was seen with MRG003 and KN046. Grade ≥ 3 trAEs were 28–60 % in ADC trials, and 3–33 % BsAb. Grade ≥ 3 myelosuppressive trAEs were typically seen in 8 ADC trials, while 4 BsAb showed infusion-related reactions (IRR). Four treatment-related deaths were reported (1 pneumonitis), all ADC trials.
Conclusion
ADC and BsAb antibodies show promise in R/M HNSCC and NPC. Results are premature by small sample sizes and lack of control arm. ADC mainly caused myelosuppression and a pneumonitis case, and BsAb IRR. Further research is warranted in this setting.
{"title":"A systematic review of antibody-drug conjugates and bispecific antibodies in head and neck squamous cell carcinoma and nasopharyngeal carcinoma: Charting the course of future therapies","authors":"Pablo Jiménez-Labaig , Antonio Rullan , Alberto Hernando-Calvo , Sandra Llop , Shreerang Bhide , Ben O’Leary , Irene Braña , Kevin J. Harrington","doi":"10.1016/j.ctrv.2024.102772","DOIUrl":"10.1016/j.ctrv.2024.102772","url":null,"abstract":"<div><h3>Introduction</h3><p>There is a need to improve the outcomes of patients with head and neck squamous cell carcinoma (HNSCC) and nasopharyngeal carcinoma (NPC), especially in recurrent unresectable and metastatic (R/M) setting. Antibody-drug conjugates (ADC) and bispecific antibodies (BsAb) may deliver promising results.</p></div><div><h3>Methods</h3><p>We conducted a systematic literature review to identify ADC and BsAb clinical trials, involving patients with HNSCC and NPC, from database creation to December 2023. We reported trial characteristics, overall response rate (ORR), overall survival (OS), and grade ≥ 3 treatment-related adverse events (trAEs).</p></div><div><h3>Results</h3><p>23 trials (65 % phase I) were found, involving 540 R/M patients (355 [20trials] HNSCC and 185 [5trials] NPC). There were 13 ADC (n = 343) and 10 BsAb (n = 197) trials. 96 % patients were refractory to standard of care treatments. ORR ranged from 0 to 100 %, with the highest ORR for GEN1042 plus chemoimmunotherapy. ORRs for monotherapies were 47 % for ADC, and 0–37 % for BsAb. MRG003 reached in HNSCC 43 % and NPC 47 %. BL-B01D1 54 % in NPC. Longest median OS was seen with MRG003 and KN046. Grade ≥ 3 trAEs were 28–60 % in ADC trials, and 3–33 % BsAb. Grade ≥ 3 myelosuppressive trAEs were typically seen in 8 ADC trials, while 4 BsAb showed infusion-related reactions (IRR). Four treatment-related deaths were reported (1 pneumonitis), all ADC trials.</p></div><div><h3>Conclusion</h3><p>ADC and BsAb antibodies show promise in R/M HNSCC and NPC. Results are premature by small sample sizes and lack of control arm. ADC mainly caused myelosuppression and a pneumonitis case, and BsAb IRR. Further research is warranted in this setting.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141184994","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}
Pub Date : 2024-05-24DOI: 10.1016/j.ctrv.2024.102771
Donatella Del Bufalo , Giovanna Damia
Ovarian carcinoma is the leading cause of gynecological cancer-related death, still with a dismal five-year prognosis, mainly due to late diagnosis and the emergence of resistance to cytotoxic and targeted agents. Bcl-2 family proteins have a key role in apoptosis and are associated with tumor development/progression and response to therapy in different cancer types, including ovarian carcinoma. In tumors, evasion of apoptosis is a possible mechanism of resistance to therapy. BH3 mimetics are small molecules that occupy the hydrophobic pocket on pro-survival proteins, allowing the induction of apoptosis, and are currently under study as single agents and/or in combination with cytotoxic and targeted agents in solid tumors. Here, we discuss recent advances in targeting anti-apoptotic proteins of the Bcl-2 family for the treatment of ovarian cancer, focusing on BH3 mimetics, and how these approaches could potentially offer an alternative/complementary way to treat patients and overcome or delay resistance to current treatments.
{"title":"Overview of BH3 mimetics in ovarian cancer","authors":"Donatella Del Bufalo , Giovanna Damia","doi":"10.1016/j.ctrv.2024.102771","DOIUrl":"10.1016/j.ctrv.2024.102771","url":null,"abstract":"<div><p>Ovarian carcinoma is the leading cause of gynecological cancer-related death, still with a dismal five-year prognosis, mainly due to late diagnosis and the emergence of resistance to cytotoxic and targeted agents. Bcl-2 family proteins have a key role in apoptosis and are associated with tumor development/progression and response to therapy in different cancer types, including ovarian carcinoma. In tumors, evasion of apoptosis is a possible mechanism of resistance to therapy. BH3 mimetics are small molecules that occupy the hydrophobic pocket on pro-survival proteins, allowing the induction of apoptosis, and are currently under study as single agents and/or in combination with cytotoxic and targeted agents in solid tumors. Here, we discuss recent advances in targeting anti-apoptotic proteins of the Bcl-2 family for the treatment of ovarian cancer, focusing on BH3 mimetics, and how these approaches could potentially offer an alternative/complementary way to treat patients and overcome or delay resistance to current treatments.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141142488","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}
Pub Date : 2024-05-23DOI: 10.1016/j.ctrv.2024.102768
Daniela Scattolin , Alessandro Dal Maso , Alessandra Ferro , Stefano Frega , Laura Bonanno , Valentina Guarneri , Giulia Pasello
Small cell lung cancer (SCLC) is characterized by a dismal prognosis. Many efforts have been made so far for identifying novel biomarkers for a personalized treatment for SCLC patients. Schlafen 11 (SLFN11) is a protein differently expressed in many cancers and recently emerged as a new potential biomarker. Lower expression of SLFN11 correlates with a worse prognosis in SCLC and other tumors. SLFN11 has a role in tumorigenesis, inducing replication arrest in the presence of DNA damage through the block of the replication fork. SLFN11 interacts also with chromatin accessibility, proteotoxic stress and mammalian target of rapamycin signalling pathway. The expression of SLFN11 is regulated by epigenetic mechanisms, including promoter methylation, histone deacetylation, and the histone methylation. The downregulation of SLFN11 correlates with a worse response to topoisomerase I and II inhibitors, alkylating agents, and poly ADP-ribose polymerase inhibitors in different cancer types. Some studies exploring strategies for overcoming drug resistance in tumors with low levels of SLFN11 showed promising results. One of these strategies includes the interaction with the Ataxia Telangiectasia and Rad3-related pathway, constitutively activated and leading to cell survival and tumor growth in the presence of low levels of SLFN11. Furthermore, the expression of SLFN11 is dynamic through time and different anticancer therapy and liquid biopsy seems to be an attractive tool for catching SLFN11 different expressions. Despite this, further investigations exploring SLFN11 as a predictive biomarker, its longitudinal changes, and new strategies to overcome drug resistances are needed.
{"title":"The emerging role of Schlafen-11 (SLFN11) in predicting response to anticancer treatments: Focus on small cell lung cancer","authors":"Daniela Scattolin , Alessandro Dal Maso , Alessandra Ferro , Stefano Frega , Laura Bonanno , Valentina Guarneri , Giulia Pasello","doi":"10.1016/j.ctrv.2024.102768","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102768","url":null,"abstract":"<div><p>Small cell lung cancer (SCLC) is characterized by a dismal prognosis. Many efforts have been made so far for identifying novel biomarkers for a personalized treatment for SCLC patients. Schlafen 11 (SLFN11) is a protein differently expressed in many cancers and recently emerged as a new potential biomarker. Lower expression of SLFN11 correlates with a worse prognosis in SCLC and other tumors. SLFN11 has a role in tumorigenesis, inducing replication arrest in the presence of DNA damage through the block of the replication fork. SLFN11 interacts also with chromatin accessibility, proteotoxic stress and mammalian target of rapamycin signalling pathway. The expression of SLFN11 is regulated by epigenetic mechanisms, including promoter methylation, histone deacetylation, and the histone methylation. The downregulation of SLFN11 correlates with a worse response to topoisomerase I and II inhibitors, alkylating agents, and poly ADP-ribose polymerase inhibitors in different cancer types. Some studies exploring strategies for overcoming drug resistance in tumors with low levels of SLFN11 showed promising results. One of these strategies includes the interaction with the Ataxia Telangiectasia and Rad3-related pathway, constitutively activated and leading to cell survival and tumor growth in the presence of low levels of SLFN11. Furthermore, the expression of SLFN11 is dynamic through time and different anticancer therapy and liquid biopsy seems to be an attractive tool for catching SLFN11 different expressions. Despite this, further investigations exploring SLFN11 as a predictive biomarker, its longitudinal changes, and new strategies to overcome drug resistances are needed.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141097794","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}
The therapeutic landscape for early breast cancer (eBC) has expanded by introducing novel anticancer agents into clinical practice. During their reproductive years, women with eBC should be informed of the potential risk of premature ovarian insufficiency (POI) and infertility with the proposed systemic therapy. Although the topic of female fertility is becoming increasingly relevant in patients with cancer, limited information is available on the gonadotoxicity of new agents available for eBC treatment. Analyses from clinical trials and prospective data on ovarian function biomarkers are lacking.
The purpose of this systematic review is to report the available preclinical and clinical data on female fertility risk with the use of the new agents that are part of clinical practice use or under development for eBC management. This review highlights the clear need to perform additional research efforts to improve our understanding on the gonoadtoxicity of new anticancer agents.
{"title":"Assessing risks and knowledge gaps on the impact of systemic therapies in early breast cancer on female fertility: A systematic review of the literature","authors":"Gabriella Gentile , Simone Scagnoli , Luca Arecco , Daniele Santini , Andrea Botticelli , Matteo Lambertini","doi":"10.1016/j.ctrv.2024.102769","DOIUrl":"10.1016/j.ctrv.2024.102769","url":null,"abstract":"<div><p>The therapeutic landscape for early breast cancer (eBC) has expanded by introducing novel anticancer agents into clinical practice. During their reproductive years, women with eBC should be informed of the potential risk of premature ovarian insufficiency (POI) and infertility with the proposed systemic therapy. Although the topic of female fertility is becoming increasingly relevant in patients with cancer, limited information is available on the gonadotoxicity of new agents available for eBC treatment. Analyses from clinical trials and prospective data on ovarian function biomarkers are lacking.</p><p>The purpose of this systematic review is to report the available preclinical and clinical data on female fertility risk with the use of the new agents that are part of clinical practice use or under development for eBC management. This review highlights the clear need to perform additional research efforts to improve our understanding on the gonoadtoxicity of new anticancer agents.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141134775","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}
Pub Date : 2024-05-22DOI: 10.1016/j.ctrv.2024.102770
Linxiaoxi Ma , Benlong Yang , Jiong Wu
Breast cancer diagnosed in premenopausal women tends to be more aggressive and the benefit of ovarian function suppression (OFS), at least in certain groups of patients, is well known. There is hesitancy in using OFS in some groups of patients who may otherwise benefit from the treatment. For instance, it is clear that in premenopausal patients with hormone receptor-positive (HR+), high-risk, early-stage breast cancer, gonadotropin-releasing hormone agonists (GnRHa) should be given in the adjuvant setting; however, confusion remains whether premenopausal patients with intermediate-risk disease benefit from GnRHa, given the lack of consensus on its definition in guidelines and clinical practice. Most recent evidence on the long-term efficacy of GnRHa, with up to 20-years of follow-up, reinforced its benefits in premenopausal patients with early-stage breast cancer. In this comprehensive review, we reviewed the long-term efficacy in terms of improvement in disease-free survival (DFS) and overall survival (OS) for early-stage HR+ breast cancer and examined evidence from multiple randomized clinical studies to identify the clinicopathological characteristics that correlated with improved DFS and OS with the addition of OFS to adjuvant endocrine therapy. Other aspects of GnRHa, including its efficacy in advanced breast cancer, safety profile, evidence in ovarian function preservation, and the advantages of long-acting formulations were also discussed. By addressing the existing gaps and grey areas regarding the inclusion of OFS as a crucial treatment component for premenopausal breast cancer patients, physicians are more aware of who to administer and the potential impact on survival outcomes.
{"title":"Revisiting ovarian function suppression with GnRH agonists for premenopausal women with breast cancer: Who should use and the impact on survival outcomes","authors":"Linxiaoxi Ma , Benlong Yang , Jiong Wu","doi":"10.1016/j.ctrv.2024.102770","DOIUrl":"10.1016/j.ctrv.2024.102770","url":null,"abstract":"<div><p>Breast cancer diagnosed in premenopausal women tends to be more aggressive and the benefit of ovarian function suppression (OFS), at least in certain groups of patients, is well known. There is hesitancy in using OFS in some groups of patients who may otherwise benefit from the treatment. For instance, it is clear that in premenopausal patients with hormone receptor-positive (HR+), high-risk, early-stage breast cancer, gonadotropin-releasing hormone agonists (GnRHa) should be given in the adjuvant setting; however, confusion remains whether premenopausal patients with intermediate-risk disease benefit from GnRHa, given the lack of consensus on its definition in guidelines and clinical practice. Most recent evidence on the long-term efficacy of GnRHa, with up to 20-years of follow-up, reinforced its benefits in premenopausal patients with early-stage breast cancer. In this comprehensive review, we reviewed the long-term efficacy in terms of improvement in disease-free survival (DFS) and overall survival (OS) for early-stage HR+ breast cancer and examined evidence from multiple randomized clinical studies to identify the clinicopathological characteristics that correlated with improved DFS and OS with the addition of OFS to adjuvant endocrine therapy. Other aspects of GnRHa, including its efficacy in advanced breast cancer, safety profile, evidence in ovarian function preservation, and the advantages of long-acting formulations were also discussed. By addressing the existing gaps and grey areas regarding the inclusion of OFS as a crucial treatment component for premenopausal breast cancer patients, physicians are more aware of who to administer and the potential impact on survival outcomes.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141131953","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}
Pub Date : 2024-05-19DOI: 10.1016/j.ctrv.2024.102767
Fionnuala Crowley , Richard Sheppard , Stephanie Lehrman , Eve Easton , Thomas U. Marron , Deborah Doroshow , Debora Afezolli
Advancements in cancer treatment have led to improved survival rates, with early phase clinical trials (EPCTs) serving as important initial steps in evaluating novel therapies. Recent studies have shown that response rates in these trials have doubled in the last twenty years. Patients who enroll on EPCTs have advanced cancer and heightened symptomatology yet maintain a robust performance status that qualifies them for clinical trial participation. It is well established that many of these patients have needs that can be addressed by palliative care, including symptom management, value assessments, advance care planning, and psychosocial and spiritual support. Several small studies have aimed to identify the most beneficial palliative care intervention for this cohort of patients, ranging from formal clinic-based multidisciplinary palliative care interventions to home-based interventions. While outcomes have trended towards benefit for patients, especially pertaining to psychological well-being, most studies were not powered to detect additional benefits for improved physical symptom management, reduction in care utilization or increased length of time on trial. In this review, we discuss the unique palliative care needs of this population and what we can learn from results of past interventional studies. We advocate for a tailored palliative care approach that acknowledges the time toxicity experienced by patients enrolled in EPCTs and address challenges posed by shortages within the palliative care workforce.
{"title":"Optimizing care in early phase cancer trials: The role of palliative care","authors":"Fionnuala Crowley , Richard Sheppard , Stephanie Lehrman , Eve Easton , Thomas U. Marron , Deborah Doroshow , Debora Afezolli","doi":"10.1016/j.ctrv.2024.102767","DOIUrl":"https://doi.org/10.1016/j.ctrv.2024.102767","url":null,"abstract":"<div><p>Advancements in cancer treatment have led to improved survival rates, with early phase clinical trials (EPCTs) serving as important initial steps in evaluating novel therapies. Recent studies have shown that response rates in these trials have doubled in the last twenty years. Patients who enroll on EPCTs have advanced cancer and heightened symptomatology yet maintain a robust performance status that qualifies them for clinical trial participation. It is well established that many of these patients have needs that can be addressed by palliative care, including symptom management, value assessments, advance care planning, and psychosocial and spiritual support. Several small studies have aimed to identify the most beneficial palliative care intervention for this cohort of patients, ranging from formal clinic-based multidisciplinary palliative care interventions to home-based interventions. While outcomes have trended towards benefit for patients, especially pertaining to psychological well-being, most studies were not powered to detect additional benefits for improved physical symptom management, reduction in care utilization or increased length of time on trial. In this review, we discuss the unique palliative care needs of this population and what we can learn from results of past interventional studies. We advocate for a tailored palliative care approach that acknowledges the time toxicity experienced by patients enrolled in EPCTs and address challenges posed by shortages within the palliative care workforce.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141078495","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}
DNA–damage repair (DDR) pathways alterations, a growing area of interest in oncology, are detected in about 20% of patient with prostate cancer and are associated with improved sensitivity to poly(ADP ribose) polymerases (PARP) inhibitors. In May 2020, the Food and Drug Administration (FDA) approved two PARP inhibitors (olaparib and rucaparib) for prostate cancer treatment. Moreover, germline aberrations in DDR pathways genes have also been related to familial or hereditary prostate cancer, requiring tailored health-care programs. These emerging scenarios are rapidly changing diagnostic, prognostic and therapeutic approaches in prostate cancer management. The aim of this review is to highlight the five W-points of DDR pathways in prostate cancer: why targeting DDR pathways in prostate cancer; what we should test for genomic profiling in prostate cancer; “where” testing genetic assessment in prostate cancer (germline or somatic, solid or liquid biopsy); when genetic testing is appropriate in prostate cancer; who could get benefit from PARP inhibitors; how improve patients outcome with combinations strategies.
{"title":"The 5-WS of targeting DNA-damage repair (DDR) pathways in prostate cancer","authors":"Annalisa Guida , Claudia Mosillo , Giulia Mammone , Claudia Caserta , Grazia Sirgiovanni , Vincenza Conteduca , Sergio Bracarda","doi":"10.1016/j.ctrv.2024.102766","DOIUrl":"10.1016/j.ctrv.2024.102766","url":null,"abstract":"<div><p>DNA–damage repair (DDR) pathways alterations, a growing area of interest in oncology, are detected in about 20% of patient with prostate cancer and are associated with improved sensitivity to poly(ADP ribose) polymerases (PARP) inhibitors. In May 2020, the Food and Drug Administration (FDA) approved two PARP inhibitors (olaparib and rucaparib) for prostate cancer treatment. Moreover, germline aberrations in DDR pathways genes have also been related to familial or hereditary prostate cancer, requiring tailored health-care programs. These emerging scenarios are rapidly changing diagnostic, prognostic and therapeutic approaches in prostate cancer management. The aim of this review is to highlight the five W-points of DDR pathways in prostate cancer: <em>why</em> targeting DDR pathways in prostate cancer; <em>what</em> we should test for genomic profiling in prostate cancer; “<em>where”</em> testing genetic assessment in prostate cancer (germline or somatic, solid or liquid biopsy); <em>when</em> genetic testing is appropriate in prostate cancer; <em>who</em> could get benefit from PARP inhibitors; <em>how</em> improve patients outcome with combinations strategies.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066544","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}
The intricate epigenetic landscape of hepatocellular carcinoma (HCC) is profoundly influenced by alterations in DNA methylation patterns. Understanding these alterations is crucial for unraveling the molecular mechanisms underlying HCC pathogenesis. Methylated circulating tumor DNA (ctDNA) presents itself as an encouraging avenue for biomarker discovery and holds substantial clinical implications in HCC management. This review comprehensively outlines the studies concerning DNA methylation in HCC and underscores the significance of methylated ctDNA within this context. Moreover, a variety of cfDNA methylation-based methodologies, such as 5hmC profiling, bisulfite-based, restriction enzyme-dependent, and enrichment-based methods, provide in-depth insights into the molecular pathology of HCC. Additionally, the integration of methylated ctDNA analysis into clinical practice represents a significant advancement in personalized HCC management. By facilitating cancer screening, prognosis assessment, and treatment response prediction, the utilization of methylated ctDNA signifies a pivotal stride toward enhancing patient care and outcomes in HCC.
{"title":"Methylated circulating tumor DNA in hepatocellular carcinoma: A comprehensive analysis of biomarker potential and clinical implications","authors":"Qian Zhu , Jiaqi Xie , Wuxuan Mei , Changchun Zeng","doi":"10.1016/j.ctrv.2024.102763","DOIUrl":"10.1016/j.ctrv.2024.102763","url":null,"abstract":"<div><p>The intricate epigenetic landscape of hepatocellular carcinoma (HCC) is profoundly influenced by alterations in DNA methylation patterns. Understanding these alterations is crucial for unraveling the molecular mechanisms underlying HCC pathogenesis. Methylated circulating tumor DNA (ctDNA) presents itself as an encouraging avenue for biomarker discovery and holds substantial clinical implications in HCC management. This review comprehensively outlines the studies concerning DNA methylation in HCC and underscores the significance of methylated ctDNA within this context. Moreover, a variety of cfDNA methylation-based methodologies, such as 5hmC profiling, bisulfite-based, restriction enzyme-dependent, and enrichment-based methods, provide in-depth insights into the molecular pathology of HCC. Additionally, the integration of methylated ctDNA analysis into clinical practice represents a significant advancement in personalized HCC management. By facilitating cancer screening, prognosis assessment, and treatment response prediction, the utilization of methylated ctDNA signifies a pivotal stride toward enhancing patient care and outcomes in HCC.</p></div>","PeriodicalId":9537,"journal":{"name":"Cancer treatment reviews","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141066463","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}