Cancer Communications最新文献

{"title":"Real-world data on ALK rearrangement test in Chinese advanced non-small cell lung cancer (RATICAL): a nationwide multicenter retrospective study","authors":"Lin Li, Wencai Li, Chunyan Wu, Yanfeng Xi, Lei Guo, Yuan Ji, Lili Jiang, Ji Li, Jingping Yun, Gang Chen, Yuan Li, Yueping Liu, Dianbin Mu, Yuchen Han, Leina Sun, Qingxin Xia, Xiaodong Teng, Nanying Che, Wei Wu, Xueshan Qiu, Chao Liu, Xiaochu Yan, Daiqiang Li, Zhihong Zhang, Zhe Wang, Yujun Li, Zheng Wang, Lingchuan Guo, Xiu Nie, Jingshu Geng, Jianhua Zhou, Jianming Ying","doi":"10.1002/cac2.12593","DOIUrl":"10.1002/cac2.12593","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Anaplastic lymphoma kinase (<i>ALK</i>) test in advanced non-small cell lung cancer (NSCLC) can help physicians provide target therapies for patients harboring <i>ALK</i> gene rearrangement. This study aimed to investigate the real-world test patterns and positive rates of <i>ALK</i> gene rearrangements in advanced NSCLC.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In this real-world study (ChiCTR2000030266), patients with advanced NSCLC who underwent an <i>ALK</i> rearrangement test in 30 medical centers in China between October 1, 2018 and December 31, 2019 were retrospectively analyzed. Interpretation training was conducted before the study was initiated. Quality controls were performed at participating centers using immunohistochemistry (IHC)-VENTANA-D5F3. The positive <i>ALK</i> gene rearrangement rate and consistency rate were calculated. The associated clinicopathological characteristics of <i>ALK</i> gene rearrangement were investigated as well.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The overall <i>ALK</i> gene rearrangement rate was 6.7% in 23,689 patients with advanced NSCLC and 8.2% in 17,436 patients with advanced lung adenocarcinoma. The quality control analysis of IHC-VENTANA-D5F3 revealed an intra-hospital consistency rate of 98.2% (879/895) and an inter-hospital consistency rate of 99.2% (646/651). IHC-VENTANA-D5F3 was used in 53.6%, real-time polymerase chain reaction (RT-PCR) in 25.4%, next-generation sequencing (NGS) in 18.3%, and fluorescence in-situ hybridization (FISH) in 15.9% in the adenocarcinoma subgroup. For specimens tested with multiple methods, the consistency rates confirmed by IHC-VENTANA-D5F3 were 98.0% (822/839) for FISH, 98.7% (1,222/1,238) for NGS, and 91.3% (146/160) for RT-PCR. The overall <i>ALK</i> gene rearrangement rates were higher in females, patients of ≤ 35 years old, never smokers, tumor cellularity of > 50, and metastatic specimens used for testing in the total NSCLC population and adenocarcinoma subgroup (all <i>P</i> < 0.05).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights the real-world variability and challenges of <i>ALK</i> test in advanced NSCLC, demonstrating a predominant use of IHC-VENTANA-D5F3 with high consistency and distinct clinicopathological features in <i>ALK</i>-positive patients. These findings underscore the need for a consensus on optimal test practices and support the development of refined <i>ALK</i> test strategies to enhance diagnostic accuracy and therapeutic decision-making in NSCLC.</p>\u0000 ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 9","pages":"992-1004"},"PeriodicalIF":20.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12593","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Central nervous system efficacy of aumolertinib versus gefitinib in patients with untreated, EGFR-mutated, advanced non-small cell lung cancer: data from a randomized phase III trial (AENEAS)","authors":"Shun Lu, Xiaorong Dong, Hong Jian, Jianhua Chen, Gongyan Chen, Yuping Sun, Yinghua Ji, Ziping Wang, Jianhua Shi, Junguo Lu, Shaoshui Chen, Dongqing Lv, Guojun Zhang, Chunling Liu, Juan Li, Xinmin Yu, Zhong Lin, Zhuang Yu, Zhehai Wang, Jiuwei Cui, Xingxiang Xu, Jian Fang, Jifeng Feng, Zhi Xu, Rui Ma, Jie Hu, Nong Yang, Xiangdong Zhou, Xiaohong Wu, Chengping Hu, Zhihong Zhang, You Lu, Yanping Hu, Liyan Jiang, Qiming wang, Renhua Guo, Jianying Zhou, Baolan Li, Chunhong Hu, Wancheng Tong, Helong Zhang, Lin Ma, Yuan Chen, Zhijun Jie, Yu Yao, Longzhen Zhang, Jie Weng, Weidong Li, Jianping Xiong, Xianwei Ye, Jianchun Duan, Haihua Yang, Meili Sun, Hongying Wei, Jiawei Wei, Zheyu Zhang, Qiong Wu","doi":"10.1002/cac2.12594","DOIUrl":"10.1002/cac2.12594","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The initial randomized, double-blinded, actively controlled, phase III ANEAS study (NCT03849768) demonstrated that aumolertinib showed superior efficacy relative to gefitinib as first-line therapy in epidermal growth factor receptor (<i>EGFR</i>)-mutated advanced non-small cell lung cancer (NSCLC). Metastatic disease in the central nervous system (CNS) remains a challenge in the management of NSCLC. This study aimed to compare the efficacy of aumolertinib versus gefitinib among patients with baseline CNS metastases in the ANEAS study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Eligible patients were enrolled and randomly assigned in a 1:1 ratio to orally receive either aumolertinib or gefitinib in a double-blinded fashion. Patients with asymptomatic, stable CNS metastases were included. Follow-up imaging of the same modality as the initial CNS imaging was performed every 6 weeks for 15 months, then every 12 weeks. CNS response was assessed by a neuroradiological blinded, independent central review (neuroradiological-BICR). The primary endpoint for this subgroup analysis was CNS progression-free survival (PFS).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Of the 429 patients enrolled and randomized in the ANEAS study, 106 patients were found to have CNS metastases (CNS Full Analysis Set, cFAS) at baseline by neuroradiological-BICR, and 60 of them had CNS target lesions (CNS Evaluable for Response, cEFR). Treatment with aumolertinib significantly prolonged median CNS PFS compared with gefitinib in both cFAS (29.0 vs. 8.3 months; hazard ratio [HR] = 0.31; 95% confidence interval [CI], 0.17-0.56; <i>P</i> < 0.001) and cEFR (29.0 vs. 8.3 months; HR = 0.26; 95% CI, 0.11-0.57; <i>P</i> < 0.001). The confirmed CNS overall response rate in cEFR was 85.7% and 75.0% in patients treated with aumolertinib and gefitinib, respectively. Competing risk analysis showed that the estimated probability of CNS progression without prior non-CNS progression or death was consistently lower with aumolertinib than with gefitinib in patients with and without CNS metastases at baseline. No new safety findings were observed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>These results indicate a potential advantage of aumolertinib over gefitinib in terms of CNS PFS and the risk of CNS progression in patients with <i>EGFR</i>-mutated advanced NSCLC with baseline CNS metastases.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Trial registration</h3>\u0000 \u0000 ","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 9","pages":"1005-1017"},"PeriodicalIF":20.1,"publicationDate":"2024-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12594","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141626090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune mediated support of metastasis: Implication for bone invasion","authors":"Zengfeng Xin,&nbsp;Luying Qin,&nbsp;Yang Tang,&nbsp;Siyu Guo,&nbsp;Fangfang Li,&nbsp;Yuan Fang,&nbsp;Gege Li,&nbsp;Yihan Yao,&nbsp;Binbin Zheng,&nbsp;Bicheng Zhang,&nbsp;Dang Wu,&nbsp;Jie Xiao,&nbsp;Chao Ni,&nbsp;Qichun Wei,&nbsp;Ting Zhang","doi":"10.1002/cac2.12584","DOIUrl":"10.1002/cac2.12584","url":null,"abstract":"<p>Bone is a common organ affected by metastasis in various advanced cancers, including lung, breast, prostate, colorectal, and melanoma. Once a patient is diagnosed with bone metastasis, the patient's quality of life and overall survival are significantly reduced owing to a wide range of morbidities and the increasing difficulty of treatment. Many studies have shown that bone metastasis is closely related to bone microenvironment, especially bone immune microenvironment. However, the effects of various immune cells in the bone microenvironment on bone metastasis remain unclear. Here, we described the changes in various immune cells during bone metastasis and discussed their related mechanisms. Osteoblasts, adipocytes, and other non-immune cells closely related to bone metastasis were also included. This review also summarized the existing treatment methods and potential therapeutic targets, and provided insights for future studies of cancer bone metastasis.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 9","pages":"967-991"},"PeriodicalIF":20.1,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12584","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141603313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellular senescence and metabolic reprogramming: Unraveling the intricate crosstalk in the immunosuppressive tumor microenvironment","authors":"Fusheng Zhang,&nbsp;Junchen Guo,&nbsp;Shengmiao Yu,&nbsp;Youwei Zheng,&nbsp;Meiqi Duan,&nbsp;Liang Zhao,&nbsp;Yihan Wang,&nbsp;Zhi Yang,&nbsp;Xiaofeng Jiang","doi":"10.1002/cac2.12591","DOIUrl":"10.1002/cac2.12591","url":null,"abstract":"<p>The intrinsic oncogenic mechanisms and properties of the tumor microenvironment (TME) have been extensively investigated. Primary features of the TME include metabolic reprogramming, hypoxia, chronic inflammation, and tumor immunosuppression. Previous studies suggest that senescence-associated secretory phenotypes that mediate intercellular information exchange play a role in the dynamic evolution of the TME. Specifically, hypoxic adaptation, metabolic dysregulation, and phenotypic shifts in immune cells regulated by cellular senescence synergistically contribute to the development of an immunosuppressive microenvironment and chronic inflammation, thereby promoting the progression of tumor events. This review provides a comprehensive summary of the processes by which cellular senescence regulates the dynamic evolution of the tumor-adapted TME, with focus on the complex mechanisms underlying the relationship between senescence and changes in the biological functions of tumor cells. The available findings suggest that components of the TME collectively contribute to the progression of tumor events. The potential applications and challenges of targeted cellular senescence-based and combination therapies in clinical settings are further discussed within the context of advancing cellular senescence-related research.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 9","pages":"929-966"},"PeriodicalIF":20.1,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12591","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141598537","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Defining and tracing subtypes of patient-derived xenograft models in pancreatic ductal adenocarcinoma","authors":"Sangyeop Hyun,&nbsp;Youngmin Han,&nbsp;Jae Yun Moon,&nbsp;Young-Ah Suh,&nbsp;Won-Gun Yun,&nbsp;Wooil Kwon,&nbsp;Jong-Eun Lee,&nbsp;Daeun Kim,&nbsp;Ja-Lok Ku,&nbsp;Jin-Young Jang,&nbsp;Daechan Park","doi":"10.1002/cac2.12585","DOIUrl":"10.1002/cac2.12585","url":null,"abstract":"&lt;p&gt;Patient-derived xenograft (PDX) models have been used to explore therapeutic opportunities for pancreatic ductal adenocarcinoma (PDAC) [&lt;span&gt;1&lt;/span&gt;]. Although original tumor characteristics are altered by cancer-stromal interactions in a PDX-specific manner [&lt;span&gt;2&lt;/span&gt;], the implications of clonal evolution from PDAC tumors to PDX are largely unknown.&lt;/p&gt;&lt;p&gt;In this study, we have conducted a comprehensive genomic analysis using 36 patient-matched PDAC tumor and PDX samples (Figure 1A). The detailed methods regarding this study are described in the Supplementary Materials. The clinical information is summarized in Supplementary Table S1. To compare the somatic mutation profiles of PDAC tumors and PDX, 33 whole exome sequencing data were analyzed by using matched patient blood as a normal control. The proportion of PDX samples with Kirsten Rat Sarcoma Viral Oncogene Homolog (&lt;i&gt;KRAS&lt;/i&gt;), Tumor Protein P53 (&lt;i&gt;TP53&lt;/i&gt;), Mothers Against Decapentaplegic Homolog 4 (&lt;i&gt;SMAD4&lt;/i&gt;), and cyclin-dependent kinase inhibitor 2A (&lt;i&gt;CDKN2A&lt;/i&gt;) mutations increased compared to PDAC tumors, indicating that cancerous clones evolved in PDX from primary tumors (Supplementary Table S2-S5, Figure 1B) [&lt;span&gt;3&lt;/span&gt;]. Specifically, the frequency of the &lt;i&gt;KRAS&lt;/i&gt; G12D mutation increased during PDX establishment, suggesting that this mutation could be responsible for driving clonal evolution in PDX models (Supplementary Table S2). Next, we observed the high correlation of the variant allele frequencies (VAFs) of commonly mutated genes between matched PDAC tumors and PDX in pairwise comparison (Figure 1C), indicating that the overall mutation rate was conserved during PDX construction. When VAFs were compared at the gene level, VAFs of driver genes significantly increased in PDX compared to primary tumors (Figure 1D). Copy number variation (CNV) profiles of protein-coding genes were also similar between the matched samples (Figure 1E, Supplementary Figure S1), while the copy numbers of driver genes became more evident in PDX compared to primary tumors (Figure 1F). Clonality analysis showed that subclones of primary tumors evolved as monoclonal or polyclonal patterns in matched PDX (Supplementary Figure S2). Despite the lack of investigations into clonal evolution over passages, these results suggest that molecular subtypes of PDX could deviate from PDAC tumors via clonal evolution during PDX model construction.&lt;/p&gt;&lt;p&gt;To investigate whether conventional PDAC subtyping is applicable to PDX, the molecular subtypes defined by Bailey &lt;i&gt;et al.&lt;/i&gt; [&lt;span&gt;5&lt;/span&gt;] were assigned to PDAC tumors and PDX. PDAC tumors were clearly clustered according to the Bailey gene signatures, showing the worst prognosis of patients with the squamous subtype as previously reported (Figure 1G). However, PDX clustering based on the Bailey gene signatures exhibited 61% (22/36) conflicting subtypes between the matched PDAC tumor and PDX samples (Supplementary Table S6). In particular","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 8","pages":"921-925"},"PeriodicalIF":20.1,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12585","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141562645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dual inhibition of sirtuins 1 and 2: reprogramming metabolic energy dynamics in chronic myeloid leukemia as an immunogenic anticancer strategy","authors":"Michael Schnekenburger,&nbsp;Anne Lorant,&nbsp;Sruthi Reddy Gajulapalli,&nbsp;Ridhika Rajora,&nbsp;Jin-Young Lee,&nbsp;Aloran Mazumder,&nbsp;Haeun Yang,&nbsp;Christo Christov,&nbsp;Hyoung Jin Kang,&nbsp;Bernard Pirotte,&nbsp;Marc Diederich","doi":"10.1002/cac2.12590","DOIUrl":"10.1002/cac2.12590","url":null,"abstract":"&lt;p&gt;Chronic myeloid leukemia (CML) is a lethal hematopoietic malignancy with a global incidence primarily attributed to the &lt;i&gt;breakpoint cluster region-Abelson&lt;/i&gt; (BCR-ABL1) fusion oncogene in over 95% of cases. The introduction of tyrosine kinase inhibitors (TKIs) has revolutionized CML management; however, a subset of patients encounters challenges such as resistance and relapse, hindering the achievement of complete remission. Overcoming these challenges in CML also requires addressing persistent leukemia stem cells (LSCs) with inherent resistance mechanisms. Key regulators of LSC metabolism, proliferation, and survival, as well as genetic and epigenetic alterations, provide potential targets [&lt;span&gt;1&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;In this study, leveraging in silico analysis (methods and descriptions of other assays are in the Supplementary file) of LSCs from CML patients at diagnosis, we demonstrated enrichment in pathways predominantly associated with proliferation, oxidative phosphorylation (OXPHOS), and metabolism, concurrently with a decrease in immune response pathways (Figure 1A). Similarly, genes negatively impacting proliferation in CML cell lines, when depleted by CRISPR, were enriched in processes related to OXPHOS, metabolism, and proliferation, mirroring the enrichment observed in LSCs (Figure 1B) [&lt;span&gt;2&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD)&lt;sup&gt;+&lt;/sup&gt;-dependent histone deacetylases. SIRT1 and SIRT2 modulate key signaling proteins impacting metabolism, survival, and stress response [&lt;span&gt;3&lt;/span&gt;]. Overexpression of SIRT1 and SIRT2 was observed in various cancers, including leukemia (Supplementary Figure S1A) [&lt;span&gt;4, 5&lt;/span&gt;]. However, our analysis of CML patients revealed variability in the expression levels of SIRT1 and SIRT2 across datasets (Supplementary Figure S1B). Given the relatively small sample sizes, we recognized the limitations of relying solely on single gene expression data, as it may not fully capture the functional relevance of SIRT1/2 in CML. In response to this limitation, we expanded our analysis to identify broader gene expression patterns associated with SIRT1/2. Specifically, we identified a CML-related network comprising 180 co-regulated transcriptional targets associated with SIRT1/2 enriched in genes relevant to leukemia (Figure 1C, Supplementary Figure S1C-E). To quantify their collective impact, we consolidated the expression of all transcripts in the SIRT1/2 regulon into a unified score, referred to as the SIRT1-2 regulon score. This score effectively discriminated between healthy hematopoietic stem cells and LSCs from CML patients at diagnosis (Figure 1D), indicating the collective impact of SIRT1 and SIRT2 on the disease.&lt;/p&gt;&lt;p&gt;Given the complementary roles of SIRT1 and 2 in regulating metabolic and survival pathways and their potential to compensate for each other's loss of function [&lt;span&gt;3&lt;/span&gt;], we postulated that exploiting metabolic vulnerabilities in LSCs throu","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 8","pages":"915-920"},"PeriodicalIF":20.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12590","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Boron neutron capture therapy of cancer: where do we stand now?","authors":"Rolf F. Barth,&nbsp;Gong Wu,&nbsp;Maria da Graca H. Vicente,&nbsp;John C Grecula,&nbsp;Nilendu Gupta","doi":"10.1002/cac2.12581","DOIUrl":"10.1002/cac2.12581","url":null,"abstract":"&lt;p&gt;This is the &lt;i&gt;third&lt;/i&gt; Editorial/Commentary that one of us (R. F. Barth) has written relating to boron neutron capture therapy (BNCT) [&lt;span&gt;1, 2&lt;/span&gt;]. For those readers who are unfamiliar with BNCT we would refer them to several recent comprehensive reviews [&lt;span&gt;3-5&lt;/span&gt;]. The &lt;i&gt;second&lt;/i&gt; Editorial ended on a hopeful note that with the introduction of accelerator-based neutron sources (ABNSs), BNCT would enter into the mainstream of radiation therapy [&lt;span&gt;2&lt;/span&gt;]. This indeed has happened most notably in Japan, where BNCT now is being used to treat patients with recurrent tumors of the head and neck region, high-grade gliomas, meningiomas and melanomas. Similarly, there has been great interest in China, as indicated by an impressive number of publications coming from both of them [&lt;span&gt;4, 6, 7&lt;/span&gt;]. In contrast to the active programs in Asia, there has been no recent clinical activity relating to BNCT in the United States and Europe. Hopefully, however, after many delays, a clinical program will be initiated in the near future in Finland using an ABNS to treat patients with recurrent tumors of the head and neck region. The obvious question is why there hasn't been interest in BNCT by clinicians in the United States and Europe? In this Editorial, we will address this question and hopefully make a convincing case for the further development of BNCT as a cancer treatment modality.&lt;/p&gt;&lt;p&gt;Why has it been so difficult to develop new boron delivery agents for BNCT? Very simply put, the requirements for such agents are very challenging [&lt;span&gt;3, 5&lt;/span&gt;]. These include (1) delivery of ∼20-30 µg &lt;sup&gt;10&lt;/sup&gt;B/g tumor; (2) high (&gt;1) tumor:normal tissue and tumor:blood boron concentration ratios during irradiation; and (3) rapid clearance of boron from normal tissues while persisting in the tumor during neutron irradiation. The intracellular localization of &lt;sup&gt;10&lt;/sup&gt;B in tumor cells is also important, and ideally, the closer to the nucleus, the better. To date, only two boron delivery agents have met many but not all of these requirements: a boron-containing derivative of phenylalanine, known as boronophenylalanine (BPA), and a polyhedral borane, known as sodium borocaptate (BSH). Finally, a major challenge in the development of effective boron delivery agents is their localization in all parts of the tumor and within all tumor cells. As reported by Elowitz et al. [&lt;span&gt;8&lt;/span&gt;] and Goodman et al. [&lt;span&gt;9&lt;/span&gt;], there was considerable variability in the boron concentrations of both BPA [&lt;span&gt;8&lt;/span&gt;] and BSH [&lt;span&gt;9&lt;/span&gt;] in multiple tissue samples taken from the same tumor. This would be especially true in brain tumors, since the blood-brain barrier limits trans-vascular entry of high-molecular weight boron delivery agents (&gt;100 Da) into the tumor.&lt;/p&gt;&lt;p&gt;Many classes of boron-containing delivery agents have been proposed, and these broadly can be divided into low-molecular weight agents, such as amino acids, pep","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 8","pages":"889-892"},"PeriodicalIF":20.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12581","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT","authors":"Rolf F. Barth,&nbsp;Nilendu Gupta,&nbsp;Shinji Kawabata","doi":"10.1002/cac2.12582","DOIUrl":"10.1002/cac2.12582","url":null,"abstract":"<p>Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form, which undergoes instantaneous nuclear fission to produce high-energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with high-grade gliomas. <i>First</i>, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. <i>Second</i>, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. <i>Third</i>, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.</p>","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 8","pages":"893-909"},"PeriodicalIF":20.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12582","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SALIRI-based (raltitrexed plus irinotecan) therapy as a second-line treatment for patients with metastatic colorectal cancer (SALLY): A prospective, multicenter, non-interventional, registry study","authors":"Shuqui Qin,&nbsp;Jin Li,&nbsp;Aiping Zhou,&nbsp;Yanqiao Zhang,&nbsp;Xianglin Yuan,&nbsp;Liangjun Zhu,&nbsp;Baoli Qin,&nbsp;Shan Zeng,&nbsp;Lin Shen,&nbsp;Ying Yuan,&nbsp;Weibo Wang,&nbsp;Jun Liang,&nbsp;Xianwen Zhang,&nbsp;Feng Ye,&nbsp;Ping Chen,&nbsp;Huaizhang Wang,&nbsp;Zhenyan Yu,&nbsp;Lu Yue,&nbsp;Yong Fang,&nbsp;Jianping Xiong,&nbsp;Jianwei Yang,&nbsp;Yiye Wan,&nbsp;Xianli Yin,&nbsp;Wenling Wang,&nbsp;Nong Xu,&nbsp;Xiaohong Wang,&nbsp;Zemin Xiao,&nbsp;Huafang Su,&nbsp;Ying Wang,&nbsp;Kangsheng Gu,&nbsp;Shuiping Tu,&nbsp;Zishu Wang,&nbsp;Bo Liu,&nbsp;Xiaohua Hu,&nbsp;Weixian Liu,&nbsp;Xiaofeng Li","doi":"10.1002/cac2.12586","DOIUrl":"10.1002/cac2.12586","url":null,"abstract":"&lt;p&gt;Primary chemotherapy options for colorectal cancer (CRC) involve four key drugs: fluorouracils (5-FU), oxaliplatin, irinotecan and raltitrexed. The first-line regimen consists of 5-FU and leucovorin combined with oxaliplatin (FOLFOX), while the second-line regimen involves 5-FU and leucovorin combined with irinotecan (FOLFIRI) for metastatic CRC (mCRC) in China [&lt;span&gt;1&lt;/span&gt;]. Efficacy findings for FOLFOX and FOLFIRI as first-line treatments reported overall response rates (ORRs) of 54% and 56%, with median progression-free survival (mPFS) of 8.0 and 8.5 months, respectively. In the second-line setting, ORRs decreased to 15% and 4%, with mPFS of 4.2 and 2.5 months, respectively, possibly indicating induced drug resistance due to repeated 5-FU infusions in both first-line and second-line treatments [&lt;span&gt;2&lt;/span&gt;]. Our present research was a prospective, non-interventional clinical trial conducted in 58 centers across China. The design and procedures are shown in the Supplementary Material. From April 2018 to March 2021, a total of 1,067 mCRC patients were enrolled for second-line treatment with raltitrexed plus irinotecan (SALIRI regimen) following unsuccessful 5-FU combined with platinum-based drug treatment, of whom 1,066 were included in the full analysis set (FAS) and 1,042 in the per-protocol set (PPS). The demographics, baseline and clinical characteristics of the patients are detailed in Supplementary Table S1.&lt;/p&gt;&lt;p&gt;The primary outcome revealed a mPFS of 7.3 months (range: 0.8-40.7, 95% confidence interval [CI]: 7.0-7.6) and a median overall survival (mOS) of 17.8 months (range: 1.4-47.3, 95% CI: 17.0-19.2) in both the FAS and PPS cohorts (Figure 1A-D, Supplementary Table S2).&lt;/p&gt;&lt;p&gt;Regarding secondary outcomes, mPFS and mOS were 5.8 (range: 0.8-34.5) and 17.0 (range: 1.8-47.3) months in the SALIRI group (&lt;i&gt;n&lt;/i&gt; = 268), whereas in the SALIRI + targeted therapy (TAR; &lt;i&gt;n&lt;/i&gt; = 795), including cetuximab (&lt;i&gt;n&lt;/i&gt; = 103), bevacizumab (&lt;i&gt;n&lt;/i&gt; = 678) or post-cetuximab + bevacizumab (&lt;i&gt;n&lt;/i&gt; = 9) or the other targeted drug group (&lt;i&gt;n&lt;/i&gt; = 5), mPFS and mOS were 7.6 (range: 0.8-40.7) and 18.1 (range: 1.4-40.7) months. A significant difference only in OS was found between SALIRI and the SALIRI + TAR groups (&lt;i&gt;P&lt;/i&gt; = 0.045) (Figure 1E-F).&lt;/p&gt;&lt;p&gt;Subsequently, the ORR and disease control rate (DCR) for the entire cohort were 19.5% and 84.2%, respectively. The best tumor response comprised 1 patient achieving a complete response (0.1%), 207 with partial responses (19.4%), 690 attaining stable disease (64.7%) and 144 experiencing progressive disease (13.5%). However, in the SALIRI + TAR group, the ORR and DCR were 20.9% (95% CI: 18.1-23.9) and 85.8% (95% CI: 83.2-88.1), whereas in the SALIRI group, the ORR and DCR were 15.7% (95% CI: 11.5-20.6) and 80.6% (95% CI: 75.4-85.2), respectively (Supplementary Table S2).&lt;/p&gt;&lt;p&gt;In addition, an exploration of PFS and OS among patients with diverse genotypes, including mutation states of rat sarco","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 8","pages":"910-914"},"PeriodicalIF":20.1,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12586","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141554219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fusobacterium is toxic for head and neck squamous cell carcinoma and its presence may determine a better prognosis","authors":"Anjali Chander,&nbsp;Jacopo Iacovacci,&nbsp;Aize Pellon,&nbsp;Rhadika Kataria,&nbsp;Anita Grigoriadis,&nbsp;John Maher,&nbsp;Cynthia Sears,&nbsp;Gilad Bachrach,&nbsp;Teresa Guerrero Urbano,&nbsp;Mary Lei,&nbsp;Imran Petkar,&nbsp;Anthony Kong,&nbsp;Tony Ng,&nbsp;Ester Orlandi,&nbsp;Nicola Alessandro Iacovelli,&nbsp;Loris De Cecco,&nbsp;Mara Serena Serafini,&nbsp;David Moyes,&nbsp;Tiziana Rancati,&nbsp;Miguel Reis Ferreira","doi":"10.1002/cac2.12588","DOIUrl":"10.1002/cac2.12588","url":null,"abstract":"&lt;p&gt;Head and neck squamous cell carcinoma (HNSCC) is a devastating disease. Despite morbid treatment, 5-year survival rates remain poor (28%-67%) [&lt;span&gt;1&lt;/span&gt;]. There is a significant knowledge gap regarding how the microbiota may impact HNSCC treatment efficacy [&lt;span&gt;2&lt;/span&gt;]. We used microbiome data from two independent cohorts to test and validate the hypothesis that oral bacteria are associated with HNSCC prognosis and in vitro models to investigate mechanistic underpinnings. Methods are detailed in Supplementary Materials.&lt;/p&gt;&lt;p&gt;We first explored associations between the relative abundance (RA) of bacterial genera and overall survival (OS) time in 155 patients with mucosal HNSCC available in the Cancer Microbiome Atlas (TCMA, Supplementary Table S1, Supplementary Text). The distribution of bacterial genera is shown in Supplementary Figure S1. Linear stepwise and Cox regression modeling evaluated associations between these genera and OS/DSS. Only &lt;i&gt;Fusobacterium&lt;/i&gt; detectability was associated with both better OS (hazard ratio [HR] = 0.35, 95% confidence interval [CI] = 0.15-0.83], &lt;i&gt;P&lt;/i&gt; = 0.018, Supplementary Figure S2A) and better disease-specific survival (DSS; 0.28 [0.15-0.83], &lt;i&gt;P&lt;/i&gt; = 0.031, Supplementary Figure S2B). Kaplan-Meier survival analysis mirrored these results (Figure 1A-B). Additionally, &lt;i&gt;Fusobacterium&lt;/i&gt; was more abundant in tumors compared to normal tissue (Supplementary Figure S3A-B), whereas a cognate Gram-negative oral commensal anaerobe, &lt;i&gt;Prevotella&lt;/i&gt;, was not (Supplementary Figure S3C-D). Receiver operating characteristic (ROC) analysis identified a &lt;i&gt;Fusobacterium&lt;/i&gt; RA cutoff of 0.016 (specificity: 92.7%; sensitivity: 28.8%). Patients with RA above the threshold had better OS and DSS (Supplementary Figure S4).&lt;/p&gt;&lt;p&gt;Next, we questioned whether any particular &lt;i&gt;Fusobacterium&lt;/i&gt; species were associated with survival. Patients were stratified into groups with detectable and undetectable species (Supplementary Figure S5). In Cox regression, only &lt;i&gt;Fusobacterium nucleatum&lt;/i&gt; detectability was significantly associated with OS (HR: 0.43 [95% CI: 0.19-0.97], &lt;i&gt;p&lt;/i&gt; = 0.042; Supplementary Figure S6). Kaplan-Meier modeling showed that &lt;i&gt;F. nucleatum&lt;/i&gt; detectability was associated with improved OS (&lt;i&gt;P&lt;/i&gt; &lt;0.001, Supplementary Figure S7A), with a trend for improved DSS (&lt;i&gt;P&lt;/i&gt; = 0.096, Supplementary Figure S7B).&lt;/p&gt;&lt;p&gt;In multivariate Cox modeling with established predictors of survival (disease stage, smoking and Human Papilloma Virus [HPV] status), both &lt;i&gt;Fusobacterium&lt;/i&gt; and &lt;i&gt;F. nucleatum&lt;/i&gt; detectability were strongly associated with OS (&lt;i&gt;P&lt;/i&gt; &lt; 0.001 for both, Supplementary Figures S8A/S9A) and DSS (&lt;i&gt;P&lt;/i&gt; &lt; 0.001 and &lt;i&gt;P&lt;/i&gt; = 0.015 for each respectively, Supplementary Figures S8B/S9B).&lt;/p&gt;&lt;p&gt;To test the validity of these results, we evaluated whether the abundance of &lt;i&gt;Fusobacterium&lt;/i&gt; was also predictive of treatment efficacy in the separate MicroLearner cohort (&lt;i&gt;","PeriodicalId":9495,"journal":{"name":"Cancer Communications","volume":"44 8","pages":"879-883"},"PeriodicalIF":20.1,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cac2.12588","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141544578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}