Background: Breast cancer is a leading cause of mortality in women. Hormone therapy plays a crucial role in treatment of hormone receptor-positive metastatic breast cancer. Elacestrant is a selective estrogen receptor degrader (SERD) that has shown promise in early-phase clinical trials. This post-hoc analysis systematically evaluates elacestrant's effectiveness in hormone receptor-positive metastatic breast cancer patients, providing insights into its efficacy, safety, and potential advantages over existing treatments.
Methods: We adhered to the PRISMA Statement 2020 guidelines and systematically searched the databases PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Embase. We conducted the post-hoc analysis using R software (V 4.3.3), applying the inverse variance method and the DerSimonian-Laird estimator to pool effect estimates with a random-effects model. We assessed heterogeneity using the Cochran's Q test and the I2 statistic.
Results: Our post-hoc analysis encompassed 3 clinical trials and a total of 835 participants. The mean age of all 835 participants across the three trials was 59.5 years (95% CI: 58.7-60.3). The pooled progression-free survival (PFS)-was estimated at 4.38 (95% CI: -7.58-16.35, P = 0.47), and the pooled objective response rate (ORR) was 7% (95% CI: 2-18%, P = 0.04), with significant heterogeneity observed among the studies.
Discussion: Elacestrant shows promise for improving outcomes in hormone receptor-positive metastatic breast cancer, but further research is needed to confirm its effectiveness. Future studies should include larger sample sizes, comprehensive phase II and III trials, and investigation of elacestrant in combination with other drugs or in preoperative settings.
{"title":"Elacestrant in hormone receptor-positive metastatic breast cancer: a post-hoc analysis.","authors":"Azza Sarfraz, Muzna Sarfraz, Faheem Javad, Musfira Khalid, Bushra Shah, Amna Gul, Mohammad Arfat Ganiyani, Areeba Ismail, Khadija Cheema","doi":"10.37349/etat.2025.1002293","DOIUrl":"10.37349/etat.2025.1002293","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer is a leading cause of mortality in women. Hormone therapy plays a crucial role in treatment of hormone receptor-positive metastatic breast cancer. Elacestrant is a selective estrogen receptor degrader (SERD) that has shown promise in early-phase clinical trials. This post-hoc analysis systematically evaluates elacestrant's effectiveness in hormone receptor-positive metastatic breast cancer patients, providing insights into its efficacy, safety, and potential advantages over existing treatments.</p><p><strong>Methods: </strong>We adhered to the PRISMA Statement 2020 guidelines and systematically searched the databases PubMed/MEDLINE, ClinicalTrials.gov, Web of Science, and Embase. We conducted the post-hoc analysis using R software (V 4.3.3), applying the inverse variance method and the DerSimonian-Laird estimator to pool effect estimates with a random-effects model. We assessed heterogeneity using the Cochran's Q test and the <i>I</i> <sup>2</sup> statistic.</p><p><strong>Results: </strong>Our post-hoc analysis encompassed 3 clinical trials and a total of 835 participants. The mean age of all 835 participants across the three trials was 59.5 years (95% CI: 58.7-60.3). The pooled progression-free survival (PFS)-was estimated at 4.38 (95% CI: -7.58-16.35, <i>P</i> = 0.47), and the pooled objective response rate (ORR) was 7% (95% CI: 2-18%, <i>P</i> = 0.04), with significant heterogeneity observed among the studies.</p><p><strong>Discussion: </strong>Elacestrant shows promise for improving outcomes in hormone receptor-positive metastatic breast cancer, but further research is needed to confirm its effectiveness. Future studies should include larger sample sizes, comprehensive phase II and III trials, and investigation of elacestrant in combination with other drugs or in preoperative settings.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002293"},"PeriodicalIF":0.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11847623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-02eCollection Date: 2025-01-01DOI: 10.37349/etat.2025.1002284
Abdullatif Taha Babakr, Mohamed Mahmoud Nour Eldein
Aim: Breast cancer (BC), a disease in which abnormal breast cells grow out of control and form tumors, is a prevalent life-threatening disease worldwide. Oxidative stress has been implicated in the development and progression of various cancers, including BC. Assessing lipid peroxidation and overall antioxidant status in BC offers valuable information on disease progression, patient prognosis, and the effectiveness of therapeutic options.
Methods: A total of 150 women were categorized into three groups: normal, benign mass, and BC. Participants were selected and evaluated at the cancer clinic; fasting blood samples were collected, and total antioxidant capacity (TAC), oxidized low-density lipoprotein (Ox-LDL), cancer antigen (CA) 15-3, and carcinoembryonic antigen (CEA) were measured. Subsequently, statistical analysis was performed to compare the levels of these parameters in different groups and examine the analytical performance of TAC and Ox-LDL in BC.
Results: In patients with malignancy, the serum level of TAC was significantly decreased compared with the benign group (8.3 U/mL and 16.04 U/mL, respectively) (P < 0.001). Healthy controls exhibited higher levels of TAC (43.4 U/mL). The levels of Ox-LDL in BC were significantly increased in both malignant and benign groups (3,831 pg/mL and 1,234 pg/mL, respectively) compared with normal controls (682 pg/mL) (P < 0.001). CEA and CA15-3 were drastically increased in the BC groups compared with the control group. A significant area under the curve was observed in the receiver operating characteristic (ROC) curve analysis for TAC (0.975, P < 0.001) and Ox-LDL (0.986, P < 0.001).
Conclusions: This study revealed that patients with BC had lower TAC and higher Ox-LDL serum levels, indicating elevated oxidative stress. These levels may serve as promising monitoring parameters in BC.
{"title":"Assessment of lipid peroxidation and total antioxidant capacity in patients with breast cancer.","authors":"Abdullatif Taha Babakr, Mohamed Mahmoud Nour Eldein","doi":"10.37349/etat.2025.1002284","DOIUrl":"https://doi.org/10.37349/etat.2025.1002284","url":null,"abstract":"<p><strong>Aim: </strong>Breast cancer (BC), a disease in which abnormal breast cells grow out of control and form tumors, is a prevalent life-threatening disease worldwide. Oxidative stress has been implicated in the development and progression of various cancers, including BC. Assessing lipid peroxidation and overall antioxidant status in BC offers valuable information on disease progression, patient prognosis, and the effectiveness of therapeutic options.</p><p><strong>Methods: </strong>A total of 150 women were categorized into three groups: normal, benign mass, and BC. Participants were selected and evaluated at the cancer clinic; fasting blood samples were collected, and total antioxidant capacity (TAC), oxidized low-density lipoprotein (Ox-LDL), cancer antigen (CA) 15-3, and carcinoembryonic antigen (CEA) were measured. Subsequently, statistical analysis was performed to compare the levels of these parameters in different groups and examine the analytical performance of TAC and Ox-LDL in BC.</p><p><strong>Results: </strong>In patients with malignancy, the serum level of TAC was significantly decreased compared with the benign group (8.3 U/mL and 16.04 U/mL, respectively) (<i>P</i> < 0.001). Healthy controls exhibited higher levels of TAC (43.4 U/mL). The levels of Ox-LDL in BC were significantly increased in both malignant and benign groups (3,831 pg/mL and 1,234 pg/mL, respectively) compared with normal controls (682 pg/mL) (<i>P</i> < 0.001). CEA and CA15-3 were drastically increased in the BC groups compared with the control group. A significant area under the curve was observed in the receiver operating characteristic (ROC) curve analysis for TAC (0.975, <i>P</i> < 0.001) and Ox-LDL (0.986, <i>P</i> < 0.001).</p><p><strong>Conclusions: </strong>This study revealed that patients with BC had lower TAC and higher Ox-LDL serum levels, indicating elevated oxidative stress. These levels may serve as promising monitoring parameters in BC.</p>","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"6 ","pages":"1002284"},"PeriodicalIF":0.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11705606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142959760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-08DOI: 10.37349/etat.2024.00248
A. Mahajan, Gurukrishna B, Shweta Wadhwa, Ujjwal Agarwal, Ujjwal Baid, Sanjay Talbar, A. Janu, Vijay Patil, V. Noronha, N. Mummudi, A. Tibdewal, JP Agarwal, Subhash Yadav, Rajiv Kumar Kaushal, A. Puranik, N. Purandare, K. Prabhash
{"title":"Correction: Deep learning based automated epidermal growth factor receptor and anaplastic lymphoma kinase status prediction of brain metastasis in non-small cell lung cancer","authors":"A. Mahajan, Gurukrishna B, Shweta Wadhwa, Ujjwal Agarwal, Ujjwal Baid, Sanjay Talbar, A. Janu, Vijay Patil, V. Noronha, N. Mummudi, A. Tibdewal, JP Agarwal, Subhash Yadav, Rajiv Kumar Kaushal, A. Puranik, N. Purandare, K. Prabhash","doi":"10.37349/etat.2024.00248","DOIUrl":"https://doi.org/10.37349/etat.2024.00248","url":null,"abstract":"","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"124 46","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141667819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.37349/etat.2024.00230
Abhilasha Sood, Arpit Mehrotra, Ujjawal Sharma, D. Aggarwal, Tejveer Singh, M. Shahwan, A. Jairoun, Isha Rani, S. Ramniwas, H. Tuli, Vikas Yadav, Manoj Kumar
In recent times, there have been notable advancements in comprehending the potential anti-cancer effects of chrysin (CH), a naturally occurring flavonoid compound found abundantly in various plant sources like honey, propolis, and certain fruits and vegetables. This active compound has garnered significant attention due to its promising therapeutic qualities and minimal toxicity. CH’s ability to combat cancer arises from its multifaceted mechanisms of action, including the initiation of apoptosis and the inhibition of proliferation, angiogenesis, metastasis, and cell cycle progression. CH also displays potent antioxidant and anti-inflammatory properties, effectively counteracting the harmful molecules that contribute to DNA damage and the development of cancer. Furthermore, CH has exhibited the potential to sensitize cancer cells to traditional chemotherapy and radiotherapy, amplifying the effectiveness of these treatments while reducing their negative impact on healthy cells. Hence, in this current review, the composition, chemistry, mechanisms of action, safety concerns of CH, along with the feasibility of its nanoformulations. To conclude, the recent investigations into CH’s anti-cancer effects present a compelling glimpse into the potential of this natural compound as a complementary therapeutic element in the array of anti-cancer approaches, providing a safer and more comprehensive method of combating this devastating ailment.
近来，人们在理解菊黄素（CH）的潜在抗癌作用方面取得了显著进展。菊黄素是一种天然黄酮类化合物，大量存在于蜂蜜、蜂胶和某些水果蔬菜等各种植物中。这种活性化合物因其良好的治疗效果和极低的毒性而备受关注。CH 的抗癌能力源于其多方面的作用机制，包括启动细胞凋亡和抑制细胞增殖、血管生成、转移和细胞周期进展。CH 还具有强大的抗氧化和抗炎特性，可有效抵消导致 DNA 损伤和癌症发展的有害分子。此外，CH 还显示出使癌细胞对传统化疗和放疗敏感的潜力，从而提高这些疗法的效果，同时减少其对健康细胞的负面影响。因此，本综述将对 CH 的成分、化学性质、作用机制、安全性问题以及其纳米制剂的可行性进行探讨。总之，最近对 CH 抗癌效果的研究让人们看到了这种天然化合物作为一系列抗癌方法中的补充治疗元素的潜力，为抗击这种毁灭性疾病提供了一种更安全、更全面的方法。
{"title":"Advancements and recent explorations of anti-cancer activity of chrysin: from molecular targets to therapeutic perspective","authors":"Abhilasha Sood, Arpit Mehrotra, Ujjawal Sharma, D. Aggarwal, Tejveer Singh, M. Shahwan, A. Jairoun, Isha Rani, S. Ramniwas, H. Tuli, Vikas Yadav, Manoj Kumar","doi":"10.37349/etat.2024.00230","DOIUrl":"https://doi.org/10.37349/etat.2024.00230","url":null,"abstract":"In recent times, there have been notable advancements in comprehending the potential anti-cancer effects of chrysin (CH), a naturally occurring flavonoid compound found abundantly in various plant sources like honey, propolis, and certain fruits and vegetables. This active compound has garnered significant attention due to its promising therapeutic qualities and minimal toxicity. CH’s ability to combat cancer arises from its multifaceted mechanisms of action, including the initiation of apoptosis and the inhibition of proliferation, angiogenesis, metastasis, and cell cycle progression. CH also displays potent antioxidant and anti-inflammatory properties, effectively counteracting the harmful molecules that contribute to DNA damage and the development of cancer. Furthermore, CH has exhibited the potential to sensitize cancer cells to traditional chemotherapy and radiotherapy, amplifying the effectiveness of these treatments while reducing their negative impact on healthy cells. Hence, in this current review, the composition, chemistry, mechanisms of action, safety concerns of CH, along with the feasibility of its nanoformulations. To conclude, the recent investigations into CH’s anti-cancer effects present a compelling glimpse into the potential of this natural compound as a complementary therapeutic element in the array of anti-cancer approaches, providing a safer and more comprehensive method of combating this devastating ailment.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"45 34","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141103762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-23DOI: 10.37349/etat.2024.00231
Nicola Normanno, Vincenza Caridi, M. Fassan, A. Avallone, Fortunato Ciardiello, C. Pinto
Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/ microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.
{"title":"Resistance to immune checkpoint inhibitors in colorectal cancer with deficient mismatch repair/microsatellite instability: misdiagnosis, pseudoprogression and/or tumor heterogeneity?","authors":"Nicola Normanno, Vincenza Caridi, M. Fassan, A. Avallone, Fortunato Ciardiello, C. Pinto","doi":"10.37349/etat.2024.00231","DOIUrl":"https://doi.org/10.37349/etat.2024.00231","url":null,"abstract":"Colorectal carcinoma (CRC) with deficiency of the deficient mismatch repair (dMMR) pathway/ microsatellite instability (MSI) is characterized by a high mutation load and infiltration of immune cells in the tumor microenvironment. In agreement with these findings, clinical trials have demonstrated a significant activity of immune checkpoint inhibitors (ICIs) in dMMR/MSI metastatic CRC (mCRC) patients and, more recently, in CRC patients with early disease undergoing neoadjuvant therapy. However, despite high response rates and durable clinical benefits, a fraction of mCRC patients, up to 30%, showed progressive disease when treated with single agent anti-programmed cell death 1 (PD-1) antibody. This article discusses the three main causes that have been associated with early progression of dMMR/MSI mCRC patients while on treatment with ICIs, i.e., misdiagnosis, pseudoprogression and tumor heterogeneity. While pseudoprogression probably does not play a relevant role, data from clinical studies demonstrate that some dMMR/MSI CRC cases with rapid progression on ICIs may be misdiagnosed, underlining the importance of correct diagnostics. More importantly, evidence suggests that dMMR/MSI mCRC is a heterogeneous group of tumors with different sensitivity to ICIs. Therefore, we propose novel diagnostic and therapeutic strategies to improve the outcome of dMMR/MSI CRC patients.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"16 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141106718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Thymic epithelial tumors (TETs) are rare malignant neoplasms arising in the thymus gland. Nevertheless, TETs, including thymomas (TMs), thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs), are the most common mediastinal malignancies overall. A multidisciplinary approach is required for the appropriate diagnostic and therapeutic management of TETs. To date, the main therapeutic strategies are largely depended on the stage of the tumor and they include surgery with or without neoadjuvant or adjuvant therapy, represented by platinum-based chemotherapy, radiotherapy or chemoradiotherapy. Immune checkpoint inhibitors (ICIs) are ongoing under evaluation in the advanced or metastatic diseases despite the challenges related to the very low tumor mutation burden (TMB) and the high incidence of immune-related adverse events in TETs. In this regard, predictive impact of tissue biomarkers expression such as programmed cell death ligand-1 (PD-L1), and other emerging biomarkers, as well as their optimal and shared interpretation are currently under evaluation in order to predict response rates to ICIs in TETs.
{"title":"Immunotherapy in thymic epithelial tumors: tissue predictive biomarkers for immune checkpoint inhibitors","authors":"Stefano Lucà, Marina Accardo, Severo Campione, Renato Franco","doi":"10.37349/etat.2024.00229","DOIUrl":"https://doi.org/10.37349/etat.2024.00229","url":null,"abstract":"Thymic epithelial tumors (TETs) are rare malignant neoplasms arising in the thymus gland. Nevertheless, TETs, including thymomas (TMs), thymic carcinomas (TCs), and thymic neuroendocrine neoplasms (TNENs), are the most common mediastinal malignancies overall. A multidisciplinary approach is required for the appropriate diagnostic and therapeutic management of TETs. To date, the main therapeutic strategies are largely depended on the stage of the tumor and they include surgery with or without neoadjuvant or adjuvant therapy, represented by platinum-based chemotherapy, radiotherapy or chemoradiotherapy. Immune checkpoint inhibitors (ICIs) are ongoing under evaluation in the advanced or metastatic diseases despite the challenges related to the very low tumor mutation burden (TMB) and the high incidence of immune-related adverse events in TETs. In this regard, predictive impact of tissue biomarkers expression such as programmed cell death ligand-1 (PD-L1), and other emerging biomarkers, as well as their optimal and shared interpretation are currently under evaluation in order to predict response rates to ICIs in TETs.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"88 20","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141116249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-25DOI: 10.37349/etat.2024.00226
Sahira Syamimi Ahmad Zawawi, Elyn Amiela Salleh, Marahaini Musa
Colorectal cancer (CRC) is a heterogeneous disease. Conventional two-dimensional (2D) culture employing cell lines was developed to study the molecular properties of CRC in vitro. Although these cell lines which are isolated from the tumor niche in which cancer develop, the translation to human model such as studying drug response is often hindered by the inability of cell lines to recapture original tumor features and the lack of heterogeneous clinical tumors represented by this 2D model, differed from in vivo condition. These limitations which may be overcome by utilizing three-dimensional (3D) culture consisting of spheroids and organoids. Over the past decade, great advancements have been made in optimizing culture method to establish spheroids and organoids of solid tumors including of CRC for multiple purposes including drug screening and establishing personalized medicine. These structures have been proven to be versatile and robust models to study CRC progression and deciphering its heterogeneity. This review will describe on advances in 3D culture technology and the application as well as the challenges of CRC-derived spheroids and organoids as a mode to screen for anticancer drugs.
{"title":"Spheroids and organoids derived from colorectal cancer as tools for in vitro drug screening","authors":"Sahira Syamimi Ahmad Zawawi, Elyn Amiela Salleh, Marahaini Musa","doi":"10.37349/etat.2024.00226","DOIUrl":"https://doi.org/10.37349/etat.2024.00226","url":null,"abstract":"Colorectal cancer (CRC) is a heterogeneous disease. Conventional two-dimensional (2D) culture employing cell lines was developed to study the molecular properties of CRC in vitro. Although these cell lines which are isolated from the tumor niche in which cancer develop, the translation to human model such as studying drug response is often hindered by the inability of cell lines to recapture original tumor features and the lack of heterogeneous clinical tumors represented by this 2D model, differed from in vivo condition. These limitations which may be overcome by utilizing three-dimensional (3D) culture consisting of spheroids and organoids. Over the past decade, great advancements have been made in optimizing culture method to establish spheroids and organoids of solid tumors including of CRC for multiple purposes including drug screening and establishing personalized medicine. These structures have been proven to be versatile and robust models to study CRC progression and deciphering its heterogeneity. This review will describe on advances in 3D culture technology and the application as well as the challenges of CRC-derived spheroids and organoids as a mode to screen for anticancer drugs.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"48 28","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140657001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.37349/etat.2024.00224
Fatima Ben Ali, Zineb Qmichou, Mohamed Oukabli, N. Dakka, Youssef Bakri, Mohammed Eddouks, Rabii Ameziane El Hassani
Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells’ survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms.
{"title":"Alteration of glucose metabolism and expression of glucose transporters in ovarian cancer","authors":"Fatima Ben Ali, Zineb Qmichou, Mohamed Oukabli, N. Dakka, Youssef Bakri, Mohammed Eddouks, Rabii Ameziane El Hassani","doi":"10.37349/etat.2024.00224","DOIUrl":"https://doi.org/10.37349/etat.2024.00224","url":null,"abstract":"Aerobic glycolysis also known as the Warburg effect, remains a hallmark of various cancers, including ovarian cancer. Cancer cells undergo metabolic changes to sustain their tumorigenic properties and adapt to environmental conditions, such as hypoxia and nutrient starvation. Altered metabolic pathways not only facilitate ovarian cancer cells’ survival and proliferation but also endow them to metastasize, develop resistance to chemotherapy, maintain cancer stem cell phenotype, and escape anti-tumor immune responses. Glucose transporters (GLUTs), which play a pivotal role as the rate-limiting step in glycolysis, are frequently overexpressed in a variety of tumors, including ovarian cancer. Multiple oncoproteins can regulate GLUT proteins, promoting tumor proliferation, migration, and metastasis, either dependent or independent of glycolysis. This review examines the alteration of GLUT proteins, particularly GLUT1, in ovarian cancer and its impact on cancer initiation, progression, and resistance to treatment. Additionally, it highlights the role of these proteins as biomarkers for diagnosis and prognosis in ovarian cancer, and delves into novel therapeutic strategies currently under development that target GLUT isoforms.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"115 23","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140659300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.37349/etat.2024.00225
L. Veronez, Luís Carlos Lopes-Júnior
In the 21st century, advances in basic research have provided new insights in the field of pediatric oncology. Pediatric patients tend to experience higher levels of distressing symptoms, which together form a symptom cluster. In clinical practice, these symptom clusters are reported daily by children and adolescents with cancer. Translational research has emerged as the translation of new knowledge from basic science into clinical practice. Understanding how neuroimmunoendocrine pathways regulate cancer development and the aspects underlying the specific therapies, such as chemotherapy and immunotherapy, is an important frontier for future research in pediatric oncology. The goal of translational research is to show how different variables in tumor and patient characteristics explain the differential effects of interventions, as translational research provides new insights into the management of cancer symptoms in children and adolescents with cancer. Together, this approach could lead to improvements in pediatric oncology care worldwide.
{"title":"Cancer symptom cluster research in pediatric oncology: a work in progress","authors":"L. Veronez, Luís Carlos Lopes-Júnior","doi":"10.37349/etat.2024.00225","DOIUrl":"https://doi.org/10.37349/etat.2024.00225","url":null,"abstract":"In the 21st century, advances in basic research have provided new insights in the field of pediatric oncology. Pediatric patients tend to experience higher levels of distressing symptoms, which together form a symptom cluster. In clinical practice, these symptom clusters are reported daily by children and adolescents with cancer. Translational research has emerged as the translation of new knowledge from basic science into clinical practice. Understanding how neuroimmunoendocrine pathways regulate cancer development and the aspects underlying the specific therapies, such as chemotherapy and immunotherapy, is an important frontier for future research in pediatric oncology. The goal of translational research is to show how different variables in tumor and patient characteristics explain the differential effects of interventions, as translational research provides new insights into the management of cancer symptoms in children and adolescents with cancer. Together, this approach could lead to improvements in pediatric oncology care worldwide.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"90 10","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140665309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24DOI: 10.37349/etat.2024.00223
Annalaura Montella, Sueva Cantalupo, Giuseppe D’alterio, Vincenzo Damiano, A. Iolascon, Mario Capasso
Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem from impaired dihydropyrimidine dehydrogenase (DPYD) enzymatic function. Emerging evidence underscores the role of single nucleotide polymorphisms (SNPs) in DPYD gene, capable of inducing DPYD activity deficiency. Consequently, DPYD genotyping’s importance is on the rise in clinical practice before initiating fluoropyrimidine treatment. Although polymerase chain reaction (PCR) followed by Sanger sequencing (SS; PCR-SS) is a prevalent method for DPYD genotyping, it may encounter limitations. In this context, there is reported a case in which a routine PCR-SS approach for genotyping DPYD SNP rs55886062 failed in a proband of African descent. The Clinical Pharmacogenetics Implementation Consortium (CPIC) categorizes the guanine (G) allele of this SNP as non-functional. The enforcement of whole genome sequencing (WGS) approach led to the identification of two adenine (A) insertions near the PCR primers annealing regions in the proband, responsible for a sequence frameshift and a genotyping error for rs55886062. These SNPs (rs145228578, 1-97981199-T-TA and rs141050810, 1-97981622-G-GA) were extremely rare in non-Finnish Europeans (0.05%) but prevalent in African populations (16%). Although limited evidence was available for these SNPs, they were catalogued as benign variants in public databases. Notably, these two SNPs exhibited a high linkage disequilibrium [LD; squared correlation coefficient (R2) = 0.98]. These findings highlighted the importance to consider the prevalence of genetic variants within diverse ethnic populations when designing primers and probes for SNP genotyping in pharmacogenetic testing. This preventive measure is essential to avoid sequence frameshifts or primer misalignments arising from SNP occurrences in the genome, which can compromise PCR-SS and lead to genotyping failures. Furthermore, this case highlights the significance of exploring alternative genotyping approaches, like WGS, when confronted with challenges associated with conventional techniques.
氟嘧啶类药物是治疗癌症的关键药物，但即使使用标准剂量，也经常会引起毒性问题。二氢嘧啶脱氢酶（DPYD）酶功能受损可能导致氟嘧啶代谢物的毒性积累，最终产生不良反应。新的证据表明，DPYD 基因中的单核苷酸多态性（SNPs）可导致 DPYD 活性缺乏。因此，在开始氟嘧啶类药物治疗前，DPYD 基因分型在临床实践中的重要性日益凸显。虽然聚合酶链式反应（PCR）后进行桑格测序（SS；PCR-SS）是一种常用的 DPYD 基因分型方法，但它可能会遇到一些限制。在这种情况下，有报告称，在一例非洲裔原告中，常规的 PCR-SS 方法未能对 DPYD SNP rs55886062 进行基因分型。临床药物遗传学实施联盟（CPIC）将该 SNP 的鸟嘌呤（G）等位基因归类为无功能基因。通过采用全基因组测序（WGS）方法，在该受试者的 PCR 引物退火区附近发现了两个腺嘌呤（A）插入物，它们是导致 rs55886062 发生序列框移位和基因分型错误的原因。这些 SNP（rs145228578，1-97981199-T-TA 和 rs141050810，1-97981622-G-GA）在非芬兰裔欧洲人中极为罕见（0.05%），但在非洲人群中却很普遍（16%）。虽然这些 SNP 的证据有限，但它们在公共数据库中被列为良性变异。值得注意的是，这两个 SNPs 表现出很高的连锁不平衡 [LD；平方相关系数 (R2) = 0.98]。这些发现突出表明，在药物基因检测中设计用于 SNP 基因分型的引物和探针时，必须考虑不同种族人群中遗传变异的流行情况。这一预防措施对于避免基因组中出现的 SNP 导致的序列框移位或引物错位至关重要，因为这可能会影响 PCR-SS，导致基因分型失败。此外，本病例还强调了在遇到与传统技术相关的挑战时，探索其他基因分型方法（如 WGS）的重要性。
{"title":"Improving single nucleotide polymorphisms genotyping accuracy for dihydropyrimidine dehydrogenase testing in pharmacogenetics","authors":"Annalaura Montella, Sueva Cantalupo, Giuseppe D’alterio, Vincenzo Damiano, A. Iolascon, Mario Capasso","doi":"10.37349/etat.2024.00223","DOIUrl":"https://doi.org/10.37349/etat.2024.00223","url":null,"abstract":"Fluoropyrimidines, crucial in cancer treatment, often cause toxicity concerns even at standard doses. Toxic accumulation of fluoropyrimidine metabolites, culminating in adverse effects, can stem from impaired dihydropyrimidine dehydrogenase (DPYD) enzymatic function. Emerging evidence underscores the role of single nucleotide polymorphisms (SNPs) in DPYD gene, capable of inducing DPYD activity deficiency. Consequently, DPYD genotyping’s importance is on the rise in clinical practice before initiating fluoropyrimidine treatment. Although polymerase chain reaction (PCR) followed by Sanger sequencing (SS; PCR-SS) is a prevalent method for DPYD genotyping, it may encounter limitations. In this context, there is reported a case in which a routine PCR-SS approach for genotyping DPYD SNP rs55886062 failed in a proband of African descent. The Clinical Pharmacogenetics Implementation Consortium (CPIC) categorizes the guanine (G) allele of this SNP as non-functional. The enforcement of whole genome sequencing (WGS) approach led to the identification of two adenine (A) insertions near the PCR primers annealing regions in the proband, responsible for a sequence frameshift and a genotyping error for rs55886062. These SNPs (rs145228578, 1-97981199-T-TA and rs141050810, 1-97981622-G-GA) were extremely rare in non-Finnish Europeans (0.05%) but prevalent in African populations (16%). Although limited evidence was available for these SNPs, they were catalogued as benign variants in public databases. Notably, these two SNPs exhibited a high linkage disequilibrium [LD; squared correlation coefficient (R2) = 0.98]. These findings highlighted the importance to consider the prevalence of genetic variants within diverse ethnic populations when designing primers and probes for SNP genotyping in pharmacogenetic testing. This preventive measure is essential to avoid sequence frameshifts or primer misalignments arising from SNP occurrences in the genome, which can compromise PCR-SS and lead to genotyping failures. Furthermore, this case highlights the significance of exploring alternative genotyping approaches, like WGS, when confronted with challenges associated with conventional techniques.","PeriodicalId":73002,"journal":{"name":"Exploration of targeted anti-tumor therapy","volume":"52 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140660658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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