Pub Date : 2025-07-01Epub Date: 2024-12-09DOI: 10.1016/j.cpt.2024.11.002
V.C. Deivayanai , P. Thamarai , S. Karishma , A. Saravanan , P.R. Yaashikaa , A.S. Vickram , R.V. Hemavathy , R Rohith Kumar , S. Rishikesavan , S. Shruthi
One in six deaths worldwide is caused by cancer, making it a major global health concern. Despite their effectiveness, traditional treatment approaches such as radiation therapy, chemotherapy, and surgery frequently have negative side effects and high costs. New approaches, such as gene therapy, are promising but are hampered by high costs and accessibility problems. Nanoparticles (NPs) facilitate targeted drug delivery by leveraging passive targeting mechanisms, such as the enhanced permeability and retention (EPR) effect, and by actively targeting surfaces with ligands for site-specific binding through the functionalization of surfaces. This approach enhances therapeutic results while lowering off-target toxicities. Notably, chemotherapeutic medications, immunotherapeutic agents, and photothermal therapies can now be delivered more precisely to the affected site using NP-based systems. By boosting particularity, reducing side effects, and tackling drug resistance, nanomedicine has the potential to revolutionize cancer treatment and ultimately advance personalized oncological care. These advancements highlight the possibilities for field growth, and future development regulations are detailed.
{"title":"Advances in nanoparticle-mediated cancer therapeutics: Current research and future perspectives","authors":"V.C. Deivayanai , P. Thamarai , S. Karishma , A. Saravanan , P.R. Yaashikaa , A.S. Vickram , R.V. Hemavathy , R Rohith Kumar , S. Rishikesavan , S. Shruthi","doi":"10.1016/j.cpt.2024.11.002","DOIUrl":"10.1016/j.cpt.2024.11.002","url":null,"abstract":"<div><div>One in six deaths worldwide is caused by cancer, making it a major global health concern. Despite their effectiveness, traditional treatment approaches such as radiation therapy, chemotherapy, and surgery frequently have negative side effects and high costs. New approaches, such as gene therapy, are promising but are hampered by high costs and accessibility problems. Nanoparticles (NPs) facilitate targeted drug delivery by leveraging passive targeting mechanisms, such as the enhanced permeability and retention (EPR) effect, and by actively targeting surfaces with ligands for site-specific binding through the functionalization of surfaces. This approach enhances therapeutic results while lowering off-target toxicities. Notably, chemotherapeutic medications, immunotherapeutic agents, and photothermal therapies can now be delivered more precisely to the affected site using NP-based systems. By boosting particularity, reducing side effects, and tackling drug resistance, nanomedicine has the potential to revolutionize cancer treatment and ultimately advance personalized oncological care. These advancements highlight the possibilities for field growth, and future development regulations are detailed.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 4","pages":"Pages 293-308"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548949","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 : 2025-07-01Epub Date: 2025-01-06DOI: 10.1016/j.cpt.2025.01.001
Yuankai Shi , Minghong Bi , Qingshan Li , Guolei Wang , Jianhua Chen , Mingjun Li , Jianhua Shi , Jiazhuan Mei , Yinghua Ji , Qingdi Xia , Yuanqing Feng , Shufeng Xu , Tongmei Zhang , Xiaohui Gao , Shubin Tang , Jie Weng , Zhuo Cao , Hongbo Wu , Xiubao Ren , Hua Xie , Sheng Yang
Background
SIBP04 is a biosimilar of bevacizumab (Avastin®, Roche, Basel, Switzerland). This study evaluated the equivalence of SIBP04 to Avastin® as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (nsqNSCLC).
Methods
In this randomized, double-blind, multi-center, phase 3 trial, we recruited patients with locally advanced or metastatic nsqNSCLC from 58 hospitals at China. Patients were randomly allocated 1:1 to receive SIBP04 or Avastin® (15 mg/kg) combined with paclitaxel (175 mg/m2) and carboplatin (area under curve [AUC] = 5.0, no more than 800 mg) (PC) regimens intravenously (3-week cycles, up to six cycles) followed by SIBP04 maintenance therapy. The primary endpoint was objective response rate (ORR), defined as the best overall response from the first dose to the 18th week, assessed by the independent review committee (IRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical equivalence of the primary endpoint was done by comparing the two-sided 90% confidence interval (CI) of the ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) in the per-protocol set (PPS) populaiton with the prespecified equivalence margin of 0.75–1.33. Secondary endpoints included progression-free survival, overall survival, duration of response, disease control rate, safety, immunogenicity, and pharmacological bioequivalence of steady-state trough concentrations.
Results
From April 17, 2020, to April 20, 2021, 517 patients were randomly assigned to receive SIBP04 plus PC (n = 259) or Avastin® plus PC (n = 258). The ORR of the SIBP04 plus PC group was 55.6% (95% CI, 49.3–61.8) and that of the Avastin® plus PC group was 59.3% (95% CI, 53.0–65.4) in the full analysis set (FAS) population (P = 0. 3944). The ORR of the SIBP04 plus PC group was 62.6% (95% CI, 55.8–69.0) and that of the Avastin® plus PC group was 64.7% (95% CI, 58.0–71.0) in the PPS population (P = 0.6448). The ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) was 0.94 (90% CI, 0.8270–1.0621) in the FAS population and 0.97 (90% CI, 0.8578–1.0900) in the PPS population, respectively, both within the prespecified equivalence margin of 0.75–1.33. Other efficacy endpoints, safety, immunogenicity, and pharmacokinetics were all comparable across the groups.
Conclusions
SIBP04 showed equivalent efficacy and safety profile to Avastin® in patients with locally advanced or metastatic nsqNSCLC. SIBP04 plus PC regimen will offer an alternative first-line treatment option for this patient population.
{"title":"Efficacy and safety of bevacizumab biosimilar SIBP04 compared with bevacizumab (Avastin®) as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer: A randomized, double-blind, phase 3 trial","authors":"Yuankai Shi , Minghong Bi , Qingshan Li , Guolei Wang , Jianhua Chen , Mingjun Li , Jianhua Shi , Jiazhuan Mei , Yinghua Ji , Qingdi Xia , Yuanqing Feng , Shufeng Xu , Tongmei Zhang , Xiaohui Gao , Shubin Tang , Jie Weng , Zhuo Cao , Hongbo Wu , Xiubao Ren , Hua Xie , Sheng Yang","doi":"10.1016/j.cpt.2025.01.001","DOIUrl":"10.1016/j.cpt.2025.01.001","url":null,"abstract":"<div><h3>Background</h3><div>SIBP04 is a biosimilar of bevacizumab (Avastin®, Roche, Basel, Switzerland). This study evaluated the equivalence of SIBP04 to Avastin® as first-line treatment for locally advanced or metastatic non-squamous non-small-cell lung cancer (nsqNSCLC).</div></div><div><h3>Methods</h3><div>In this randomized, double-blind, multi-center, phase 3 trial, we recruited patients with locally advanced or metastatic nsqNSCLC from 58 hospitals at China. Patients were randomly allocated 1:1 to receive SIBP04 or Avastin® (15 mg/kg) combined with paclitaxel (175 mg/m<sup>2</sup>) and carboplatin (area under curve [AUC] = 5.0, no more than 800 mg) (PC) regimens intravenously (3-week cycles, up to six cycles) followed by SIBP04 maintenance therapy. The primary endpoint was objective response rate (ORR), defined as the best overall response from the first dose to the 18th week, assessed by the independent review committee (IRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Clinical equivalence of the primary endpoint was done by comparing the two-sided 90% confidence interval (CI) of the ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) in the per-protocol set (PPS) populaiton with the prespecified equivalence margin of 0.75–1.33. Secondary endpoints included progression-free survival, overall survival, duration of response, disease control rate, safety, immunogenicity, and pharmacological bioequivalence of steady-state trough concentrations.</div></div><div><h3>Results</h3><div>From April 17, 2020, to April 20, 2021, 517 patients were randomly assigned to receive SIBP04 plus PC (<em>n</em> = 259) or Avastin® plus PC (<em>n</em> = 258). The ORR of the SIBP04 plus PC group was 55.6% (95% CI, 49.3–61.8) and that of the Avastin® plus PC group was 59.3% (95% CI, 53.0–65.4) in the full analysis set (FAS) population (<em>P</em> = 0. 3944). The ORR of the SIBP04 plus PC group was 62.6% (95% CI, 55.8–69.0) and that of the Avastin® plus PC group was 64.7% (95% CI, 58.0–71.0) in the PPS population (<em>P</em> = 0.6448). The ORR ratio (SIBP04 plus PC vs. Avastin® plus PC) was 0.94 (90% CI, 0.8270–1.0621) in the FAS population and 0.97 (90% CI, 0.8578–1.0900) in the PPS population, respectively, both within the prespecified equivalence margin of 0.75–1.33. Other efficacy endpoints, safety, immunogenicity, and pharmacokinetics were all comparable across the groups.</div></div><div><h3>Conclusions</h3><div>SIBP04 showed equivalent efficacy and safety profile to Avastin® in patients with locally advanced or metastatic nsqNSCLC. SIBP04 plus PC regimen will offer an alternative first-line treatment option for this patient population.</div></div><div><h3>Trial registration</h3><div>Clinicaltrials.gov, identifier NCT05318443.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 4","pages":"Pages 337-345"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548952","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 : 2025-07-01Epub Date: 2024-12-18DOI: 10.1016/j.cpt.2024.12.002
Yutong Wang , Qiming Xu , Yuan Li , Yongbin Su , Ling Wang , Xiaoquan Wang , Jian Ge , Hongmei Jing , Yuxing Guo , Yalin Chen , Xianan Li , Jun-ling Zhuang , Jing Tan , Xiaobo Wang , Liye Zhong , Jun Luo , Peng Zhao , Shengjin Fan , Jinhai Ren , Haiping Yang , Li Bao
This consensus on multiple myeloma-related bone diseases (MBDs) underscores the importance of a multidisciplinary approach that encompasses hematology, radiology, orthopedics, and additional specialties to tackle its intricate challenges. MBD, a prevalent and debilitating complication of multiple myeloma, leads to bone pain, fractures, and skeletal-related events (SREs), which profoundly impact patients’ quality of life. The guidelines offer a thorough framework for diagnosis, treatment, and continual assessment, emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). Treatment strategies prioritize the careful application of anti-myeloma agents, bisphosphonates, and denosumab to minimize bone loss and decrease SRE risk, complemented by surgical and radiotherapy interventions for structural or pain-related issues. Supportive care measures, including pain management, rehabilitation, nutritional support, and dental evaluations, play a crucial role in enhancing patient outcomes and preserving quality of life. This consensus advocates a standardized, evidence-based approach to managing MBD, ensuring comprehensive and coordinated care for patients.
{"title":"Expert consensus on a multidisciplinary approach for the management of multiple myeloma-related bone disease","authors":"Yutong Wang , Qiming Xu , Yuan Li , Yongbin Su , Ling Wang , Xiaoquan Wang , Jian Ge , Hongmei Jing , Yuxing Guo , Yalin Chen , Xianan Li , Jun-ling Zhuang , Jing Tan , Xiaobo Wang , Liye Zhong , Jun Luo , Peng Zhao , Shengjin Fan , Jinhai Ren , Haiping Yang , Li Bao","doi":"10.1016/j.cpt.2024.12.002","DOIUrl":"10.1016/j.cpt.2024.12.002","url":null,"abstract":"<div><div>This consensus on multiple myeloma-related bone diseases (MBDs) underscores the importance of a multidisciplinary approach that encompasses hematology, radiology, orthopedics, and additional specialties to tackle its intricate challenges. MBD, a prevalent and debilitating complication of multiple myeloma, leads to bone pain, fractures, and skeletal-related events (SREs), which profoundly impact patients’ quality of life. The guidelines offer a thorough framework for diagnosis, treatment, and continual assessment, emphasizing early detection and consistent monitoring using imaging techniques such as positron emission tomography-computed tomography (PET-CT) and magnetic resonance imaging (MRI). Treatment strategies prioritize the careful application of anti-myeloma agents, bisphosphonates, and denosumab to minimize bone loss and decrease SRE risk, complemented by surgical and radiotherapy interventions for structural or pain-related issues. Supportive care measures, including pain management, rehabilitation, nutritional support, and dental evaluations, play a crucial role in enhancing patient outcomes and preserving quality of life. This consensus advocates a standardized, evidence-based approach to managing MBD, ensuring comprehensive and coordinated care for patients.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 4","pages":"Pages 280-292"},"PeriodicalIF":0.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144548948","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 : 2025-05-01Epub Date: 2024-09-26DOI: 10.1016/j.cpt.2024.09.006
Xingbin Hu , Wenhao Ouyang , Haizhu Chen , Zhihong Liu , Zijia Lai , Herui Yao
Background
Gastric cancer (GC) is a common malignancy characterized by the absence of reliable prognostic indicators and effective therapeutic targets. Claudin-9 (CLDN9) has been demonstrated to be upregulated in various cancers. However, its prognostic value, biological function, and regulatory mechanisms in GC remain unclear. Therefore, this study aimed to elucidate the role of CLDN9 in GC progression and its underlying mechanisms.
Methods
We utilized consensus cluster, random survival forest, and multivariate Cox regression analyses to identify CLDN9 in GC. Subsequently, we evaluated the mRNA and protein levels of CLDN9 in GC using quantitative real-time polymerase chain reaction (PCR) (qRT-PCR), Western blotting (WB), and immunohistochemistry (IHC). Furthermore, the role of CLDN9 in GC progression was investigated using a series of functional in vivo and in vitro experiments. Finally, we elucidated the molecular mechanisms of CLDN9 using bioinformatics, molecular biology, animal models, and patient tissue specimens.
Results
Two GC subtypes with survival and functional differences were identified based on glycolytic metabolic genes in the Cancer Genome Atlas (TCGA)- Stomach adenocarcinoma (STAD) dataset. A prognostic risk score was calculated using seven genes to assess the overall survival (OS) in GC. Using random survival forest and multivariate Cox analyses, we identified CLDN9 as the key gene linked to the glycolytic subtype and prognosis of GC. CLDN9 expression was significantly upregulated in patients with GC as well as in GC cells. CLDN9 knockdown inhibited tumor proliferation, invasion, and metastasis both in vivo and in vitro. Mechanistically, CLDN9 was found to regulate lactate dehydrogenase A (LDHA) expression and promote glycolytic metabolism by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF1α) signaling pathway. Additionally, lactate, a glycolytic metabolite, enhanced programmed cell death ligand 1 (PD-L1) lactylation and stability, which suppressed anti-tumor immunity in CD8+ T cells, thereby contributing to GC progression.
Conclusions
CLDN9 expression is associated with GC development and progression. Mechanistically, CLDN9 enhances the glycolysis pathway and facilitates PD-L1 lactylation through the PI3K/AKT/HIF1α signaling pathway, thereby suppressing anti-tumor immunity in CD8+ T cells. CLDN9 has the potential to serve as a novel prognostic marker and therapeutic target for GC.
{"title":"Claudin-9 (CLDN9) promotes gastric cancer progression by enhancing the glycolysis pathway and facilitating PD-L1 lactylation to suppress CD8+ T cell anti-tumor immunity","authors":"Xingbin Hu , Wenhao Ouyang , Haizhu Chen , Zhihong Liu , Zijia Lai , Herui Yao","doi":"10.1016/j.cpt.2024.09.006","DOIUrl":"10.1016/j.cpt.2024.09.006","url":null,"abstract":"<div><h3>Background</h3><div>Gastric cancer (GC) is a common malignancy characterized by the absence of reliable prognostic indicators and effective therapeutic targets. Claudin-9 (CLDN9) has been demonstrated to be upregulated in various cancers. However, its prognostic value, biological function, and regulatory mechanisms in GC remain unclear. Therefore, this study aimed to elucidate the role of <em>CLDN9</em> in GC progression and its underlying mechanisms.</div></div><div><h3>Methods</h3><div>We utilized consensus cluster, random survival forest, and multivariate Cox regression analyses to identify <em>CLDN9</em> in GC. Subsequently, we evaluated the mRNA and protein levels of <em>CLDN9</em> in GC using quantitative real-time polymerase chain reaction (PCR) (qRT-PCR), Western blotting (WB), and immunohistochemistry (IHC). Furthermore, the role of <em>CLDN9</em> in GC progression was investigated using a series of functional <em>in vivo</em> and <em>in vitro</em> experiments. Finally, we elucidated the molecular mechanisms of <em>CLDN9</em> using bioinformatics, molecular biology, animal models, and patient tissue specimens.</div></div><div><h3>Results</h3><div>Two GC subtypes with survival and functional differences were identified based on glycolytic metabolic genes in the Cancer Genome Atlas (TCGA)- Stomach adenocarcinoma (STAD) dataset. A prognostic risk score was calculated using seven genes to assess the overall survival (OS) in GC. Using random survival forest and multivariate Cox analyses, we identified <em>CLDN9</em> as the key gene linked to the glycolytic subtype and prognosis of GC. <em>CLDN9</em> expression was significantly upregulated in patients with GC as well as in GC cells. <em>CLDN9</em> knockdown inhibited tumor proliferation, invasion, and metastasis both <em>in vivo</em> and <em>in vitro</em>. Mechanistically, <em>CLDN9</em> was found to regulate lactate dehydrogenase A (LDHA) expression and promote glycolytic metabolism by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/hypoxia-inducible factor 1-alpha (HIF1α) signaling pathway. Additionally, lactate, a glycolytic metabolite, enhanced programmed cell death ligand 1 (PD-L1) lactylation and stability, which suppressed anti-tumor immunity in CD8<sup>+</sup> T cells, thereby contributing to GC progression.</div></div><div><h3>Conclusions</h3><div><em>CLDN9</em> expression is associated with GC development and progression. Mechanistically, <em>CLDN9</em> enhances the glycolysis pathway and facilitates PD-L1 lactylation through the PI3K/AKT/HIF1α signaling pathway, thereby suppressing anti-tumor immunity in CD8<sup>+</sup> T cells. <em>CLDN9</em> has the potential to serve as a novel prognostic marker and therapeutic target for GC.</div></div>","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 3","pages":"Pages 253-266"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887014","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 : 2025-05-01Epub Date: 2025-03-04DOI: 10.1016/j.cpt.2025.03.001
Gnanaprakash Jeyaraj
{"title":"Commentary on the “Relationship between visceral obesity and prognosis in patients with stage IVB cervical cancer receiving radiotherapy and chemotherapy”","authors":"Gnanaprakash Jeyaraj","doi":"10.1016/j.cpt.2025.03.001","DOIUrl":"10.1016/j.cpt.2025.03.001","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 3","pages":"Pages 269-270"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887012","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 : 2025-05-01Epub Date: 2024-09-21DOI: 10.1016/j.cpt.2024.09.005
Yintao Li, Jianxin Xue, Li Zhang
{"title":"New advances in lung cancer treatment: Efficacy, safety, and future research directions","authors":"Yintao Li, Jianxin Xue, Li Zhang","doi":"10.1016/j.cpt.2024.09.005","DOIUrl":"10.1016/j.cpt.2024.09.005","url":null,"abstract":"","PeriodicalId":93920,"journal":{"name":"Cancer pathogenesis and therapy","volume":"3 3","pages":"Pages 181-182"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143887142","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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