Cancer Science最新文献

{"title":"Serial comprehensive genomic profiling by next-generation sequencing for patients with metastatic colorectal cancer","authors":"Steven Olsen, Yoshiaki Nakamura","doi":"10.1111/cas.16016","DOIUrl":"10.1111/cas.16016","url":null,"abstract":"<p>To The Editor,</p><p>With the increasing number of potentially actionable genomic alterations to be assessed, comprehensive genomic profiling (CGP) using next-generation sequencing (NGS) has become more common for patients with advanced-stage cancers. International practice guidelines recommend CGP over single-gene testing, particularly when tissue is difficult to obtain or when therapies are available for multiple genomic targets.<span><sup>1, 2</sup></span></p><p>In Japan, CGP for advanced cancer is covered by national health insurance only after completion of standard therapy and only once in a patient's lifetime. Recent data on the use of first-line CGP for advanced solid tumors in Japan has prompted interest in earlier use of such technology.<span><sup>3</sup></span></p><p>If CGP were to move to earlier lines of testing in Japan, what might be the clinical value for testing patients again by CGP after disease progression? We considered metastatic colorectal cancer (mCRC) as a model for two reasons: (1) It is the most registered tumor type with the Japanese Center for Cancer Genomics and Therapeutics (C-CAT),<span><sup>4</sup></span> and (2) international clinical practice guidelines recommend testing for the presence of multiple genomic biomarkers prior to treatment for patients with mCRC. These include mutations in <i>KRAS</i> and <i>NRAS</i>, <i>BRAF</i> V600E, <i>ERBB2</i> amplification, <i>NTRK</i> and <i>RET</i> fusions, and microsatellite instability-high (MSI-high) or mismatch repair deficiency.<span><sup>1, 2, 5</sup></span></p><p>We published findings from a real-world claims database of 1064 mCRC patients tested by a plasma-based NGS CGP assay after completion of first- or second-line therapy in the United States.<span><sup>6</sup></span> In this setting, plasma-based NGS testing of circulating tumor DNA (ctDNA) performs similarly to standard tumor tissue testing<span><sup>7</sup></span> and tissue-based NGS<span><sup>8</sup></span> with a high negative predictive value for the absence of <i>RAS</i> mutations, particularly in plasma samples having a non-<i>RAS</i> mutation with variant allelic frequency (VAF) ≥1%.<span><sup>9</sup></span> Therefore, we considered that this cohort could be useful for exploring the role of serial CGP testing for patients with mCRC.</p><p>From the same dataset used for our previous manuscript we identified 82 patients who were tested by CGP prior to two different lines of systemic anticancer therapy within the first three lines of treatment. Among these, 34 were tested prior to first- and second-line therapy, 12 prior to first- and third-line therapy, and 36 prior to second- and third-line therapy.</p><p>For this post hoc analysis, we employed the definition of actionability and matched therapy as previously described<span><sup>6</sup></span> but with a more conservative approach for determination of actionable <i>RAS</i> wild-type status; namely, absence of <i>KRAS</i> or <i>NRAS</i> mutations in ","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"321-323"},"PeriodicalIF":5.7,"publicationDate":"2023-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72211443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-HTLV-1 immunity combined with proviral load as predictive biomarkers for adult T-cell leukemia-lymphoma","authors":"Asami Yamada,&nbsp;Jun-ichirou Yasunaga,&nbsp;Lihan Liang,&nbsp;Wenyi Zhang,&nbsp;Junya Sunagawa,&nbsp;Shinji Nakaoka,&nbsp;Shingo Iwami,&nbsp;Yasunori Kogure,&nbsp;Yuta Ito,&nbsp;Keisuke Kataoka,&nbsp;Masanori Nakagawa,&nbsp;Masako Iwanaga,&nbsp;Atae Utsunomiya,&nbsp;Ki-Ryang Koh,&nbsp;Toshiki Watanabe,&nbsp;Kisato Nosaka,&nbsp;Masao Matsuoka","doi":"10.1111/cas.15997","DOIUrl":"10.1111/cas.15997","url":null,"abstract":"<p>Human T-cell leukemia virus type 1 (HTLV-1) establishes chronic infection in humans and induces a T-cell malignancy called adult T-cell leukemia-lymphoma (ATL) and several inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Persistent HTLV-1 infection is established under the pressure of host immunity, and therefore the immune response against HTLV-1 is thought to reflect the status of the disease it causes. Indeed, it is known that cellular immunity against viral antigens is suppressed in ATL patients compared to HAM/TSP patients. In this study, we show that profiling the humoral immunity to several HTLV-1 antigens, such as Gag, Env, and Tax, and measuring proviral load are useful tools for classifying disease status and predicting disease development. Using targeted sequencing, we found that several carriers whom this profiling method predicted to be at high risk for developing ATL indeed harbored driver mutations of ATL. The clonality of HTLV-1-infected cells in those carriers was still polyclonal; it is consistent with an early stage of leukemogenesis. Furthermore, this study revealed significance of anti-Gag proteins to predict high risk group in HTLV-1 carriers. Consistent with this finding, anti-Gag cytotoxic T lymphocytes (CTLs) were increased in patients who received hematopoietic stem cell transplantation and achieved remission state, indicating the significance of anti-Gag CTLs for disease control. Our findings suggest that our strategy that combines anti-HTLV-1 antibodies and proviral load may be useful for prediction of the development of HTLV-1-associated diseases.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"310-320"},"PeriodicalIF":5.7,"publicationDate":"2023-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72211442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antitumor activities against breast cancers by an afucosylated anti-HER2 monoclonal antibody H2Mab-77-mG2a-f","authors":"Tomohiro Tanaka,&nbsp;Hiroyuki Suzuki,&nbsp;Tomokazu Ohishi,&nbsp;Mika K. Kaneko,&nbsp;Yukinari Kato","doi":"10.1111/cas.16008","DOIUrl":"10.1111/cas.16008","url":null,"abstract":"<p>Breast cancer patients with high levels of human epidermal growth factor receptor 2 (HER2) expression have worse clinical outcomes. Anti-HER2 monoclonal antibody (mAb) is the most important therapeutic modality for HER2-positive breast cancer. We previously immunized mice with the ectodomain of HER2 to create the anti-HER2 mAb, H₂Mab-77 (mouse IgG₁, kappa). This was then altered to produce H₂Mab-77-mG_2a-f, an afucosylated mouse IgG_2a. In the present work, we examined the reactivity of H₂Mab-77-mG_2a-f and antitumor effects against breast cancers in vitro and in vivo. BT-474, an endogenously HER2-expressing breast cancer cell line, was identified by H₂Mab-77-mG_2a-f with a strong binding affinity (a dissociation constant [<i>K</i>_D]: 5.0 × 10⁻⁹ M). H₂Mab-77-mG_2a-f could stain HER2 of breast cancer tissues in immunohistochemistry and detect HER2 protein in Western blot analysis. Furthermore, H₂Mab-77-mG_2a-f demonstrated strong antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) for BT-474 cells. MDA-MB-468, a HER2-negative breast cancer cell line, was unaffected by H₂Mab-77-mG_2a-f. Additionally, in the BT-474-bearing tumor xenograft model, H₂Mab-77-mG_2a-f substantially suppressed tumor development when compared with the control mouse IgG_2a mAb. In contrast, the HER2-negative MDA-MB-468-bearing tumor xenograft model showed no response to H₂Mab-77-mG_2a-f. These findings point to the possibility of H₂Mab-77-mG_2a-f as a treatment regimen by showing that it has antitumor effects on HER2-positive breast tumors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"298-309"},"PeriodicalIF":5.7,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823288/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523079","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection and clinical significance of CEACAM5 methylation in colorectal cancer patients","authors":"Sheng-Chieh Huang,&nbsp;Shih-Ching Chang,&nbsp;Tsai-Tsen Liao,&nbsp;Muh-Hwa Yang","doi":"10.1111/cas.16012","DOIUrl":"10.1111/cas.16012","url":null,"abstract":"<p>Colorectal cancer (CRC) is a globally common cancer, and the serum carcinoembryonic antigen (sCEA) is widely applied as a diagnostic and prognostic tumor marker in CRC. This study aimed to elucidate the mechanism of CEA expression and corresponding clinical features to improve prognostic assessments. In CRC cells, hypomethylation of the <i>CEACAM5</i> promoter enhanced CEA expression in HCT116 and HT29 cells with 5-aza-2′-deoxycytidine (5-Aza-dC) treatment. Our clinical data indicated that 64.7% (101/156) of CRC patients had an sCEA level above the normal range, and 76.2% (77/101) of those patients showed a lower average CpG methylation level of the <i>CEACAM5</i> promoter. The methylation analysis showed that both CRC cell lines and patient samples shared the same critical methylation CpG regions at −200 to −500 and −1000 to −1400 bp of the <i>CEACAM5</i> promoter. Patients with hypermethylation of the <i>CEACAM5</i> promoter showed features of a <i>BRAF</i> mutation, <i>TGFB2</i> mutation, microsatellite instability-high, and preference for right-sided colorectal cancer and peritoneal seeding presentation that had a similar clinical character to the consensus molecular subtype 1 (CMS1) of colorectal cancer. Additionally, hypermethylation of the <i>CEACAM5</i> promoter combined with evaluated sCEA demonstrated the worst survival among the patients. Therefore, the methylation status of the <i>CEACAM5</i> promoter also served as an effective biomarker for assessing disease prognosis. Results indicated that DNA methylation is a major regulatory mechanism for CEA expression in colorectal cancer. Moreover, our data also highlighted that patients in a subgroup who escaped from inactivation by DNA methylation had distinct clinical and pathological features and the worst survival.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"270-282"},"PeriodicalIF":5.7,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CircBRD7 attenuates tumor growth and metastasis in nasopharyngeal carcinoma via epigenetic activation of its host gene","authors":"Jianxia Wei,&nbsp;Mengna Li,&nbsp;Shipeng Chen,&nbsp;Changning Xue,&nbsp;Lemei Zheng,&nbsp;Yumei Duan,&nbsp;Hongyu Deng,&nbsp;Songqing Fan,&nbsp;Wei Xiong,&nbsp;Ming Zhou","doi":"10.1111/cas.15998","DOIUrl":"10.1111/cas.15998","url":null,"abstract":"<p>BRD7 was identified as a tumor suppressor in nasopharyngeal carcinoma (NPC). Circular RNAs (CircRNAs) are involved in the occurrence and development of NPC as oncogenes or tumor suppressors. However, the function and mechanism of the circular RNA forms derived from BRD7 in NPC are not well understood. In this study, we first identified that circBRD7 was a novel circRNA derived from BRD7 that inhibited cell proliferation, migration, invasion of NPC cells, as well as the xenograft tumor growth and metastasis in vivo. Mechanistically, circBRD7 promoted the transcriptional activation and expression of BRD7 by enhancing the enrichment of histone 3 lysine 27 acetylation (H3K27ac) in the promoter region of its host gene BRD7, and BRD7 promoted the formation of circBRD7. Therefore, circBRD7 formed a positive feedback loop with BRD7 to inhibit NPC development and progression. Moreover, restoration of BRD7 expression rescued the inhibitory effect of circBRD7 on the malignant progression of NPC. In addition, circBRD7 demonstrated low expression in NPC tissues, which was positively correlated with BRD7 expression and negatively correlated with the clinical stage of NPC patients. Taken together, circBRD7 attenuates the tumor growth and metastasis of NPC by forming a positive feedback loop with its host gene BRD7, and targeting the circBRD7/BRD7 axis is a promising strategy for the clinical diagnosis and treatment of NPC.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"139-154"},"PeriodicalIF":5.7,"publicationDate":"2023-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71523080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Newly developed preclinical models reveal broad-spectrum CDK inhibitors as potent drugs for CRPC exhibiting primary resistance to enzalutamide","authors":"Takashi Matsuoka,&nbsp;Aiko Sugiyama,&nbsp;Yoshifumi Miyawaki,&nbsp;Yusuke Hidaka,&nbsp;Yukiko Okuno,&nbsp;Hiroaki Sakai,&nbsp;Hiroki Tanaka,&nbsp;Kiyotsugu Yoshikawa,&nbsp;Tomohiro Fukui,&nbsp;Kei Mizuno,&nbsp;Takayuki Sumiyoshi,&nbsp;Takayuki Goto,&nbsp;Takahiro Inoue,&nbsp;Shusuke Akamatsu,&nbsp;Takashi Kobayashi,&nbsp;Eijiro Nakamura","doi":"10.1111/cas.15984","DOIUrl":"10.1111/cas.15984","url":null,"abstract":"<p>Androgen-deprivation therapy is a standard treatment for advanced prostate cancer. However, most patients eventually acquire resistance and progress to castration-resistant prostate cancer (CRPC). In this study, we established new CRPC cell lines, AILNCaP14 and AILNCaP15, from LNCaP cells under androgen-deprived conditions. Unlike most pre-existing CRPC cell lines, both cell lines expressed higher levels of androgen receptor (AR) and prostate-specific antigen (PSA) than parental LNCaP cells. Moreover, these cells exhibited primary resistance to enzalutamide. Since AR signaling plays a significant role in the development of CRPC, PSA promoter sequences fused with GFP were introduced into AILNCaP14 cells to conduct GFP fluorescence-based chemical screening. We identified flavopiridol, a broad-spectrum CDK inhibitor, as a candidate drug that could repress AR transactivation of CRPC cells, presumably through the inhibition of phosphorylation of AR on the serine 81 residue (pAR^Ser81). Importantly, this broad-spectrum CDK inhibitor inhibited the proliferation of AILNCaP14 cells both in vitro and in vivo. Moreover, a newly developed liver metastatic model using AILNCaP15 cells revealed that the compound attenuated tumor growth of CRPC harboring highly metastatic properties. Finally, we developed a patient-derived xenograft (PDX) model of CRPC and DCaP CR from a patient presenting therapeutic resistance to enzalutamide, abiraterone, and docetaxel. Flavopiridol successfully suppressed the tumor growth of CRPC in this PDX model. Since AR^Ser81 was found to be phosphorylated in clinical CRPC samples, our data suggested that broad-spectrum CDK inhibitors might be a potent candidate drug for the treatment of CRPC, including those exhibiting primary resistance to enzalutamide.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"283-297"},"PeriodicalIF":5.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71487832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcutaneous epcoritamab monotherapy in Japanese adults with relapsed/refractory diffuse large B-cell lymphoma","authors":"Koji Izutsu,&nbsp;Takahiro Kumode,&nbsp;Junichiro Yuda,&nbsp;Hirokazu Nagai,&nbsp;Yuko Mishima,&nbsp;Youko Suehiro,&nbsp;Kazuhito Yamamoto,&nbsp;Tomoaki Fujisaki,&nbsp;Kenji Ishitsuka,&nbsp;Kenichi Ishizawa,&nbsp;Takayuki Ikezoe,&nbsp;Momoko Nishikori,&nbsp;Daigo Akahane,&nbsp;Jiro Fujita,&nbsp;Minh Dinh,&nbsp;David Soong,&nbsp;Hidehisa Noguchi,&nbsp;Jeppe Klint Buchbjerg,&nbsp;Elena Favaro,&nbsp;Noriko Fukuhara","doi":"10.1111/cas.15996","DOIUrl":"10.1111/cas.15996","url":null,"abstract":"<p>Epcoritamab is a subcutaneously administered CD3xCD20 bispecific Ab that showed deep, durable responses with a manageable safety profile in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the global multicenter pivotal phase II trial EPCORE NHL-1. Here, we present results from the similar EPCORE NHL-3 phase I/II trial evaluating epcoritamab monotherapy in Japanese patients with R/R CD20⁺ B-cell non-Hodgkin's lymphoma previously treated with two or more lines of therapy. Epcoritamab was dosed subcutaneously in 28-day cycles; once weekly during cycles 1–3, every 2 weeks during cycles 4–9, and every 4 weeks from cycle 10 until disease progression or unacceptable toxicity. Step-up dosing and cytokine release syndrome (CRS) prophylaxis were used during treatment cycle 1. As of January 31, 2022, 36 patients received treatment with 48 mg epcoritamab monotherapy. At a median follow-up of 8.4 months, overall response and complete response rates by independent review committee were 55.6% and 44.4%, respectively. The median duration of response, duration of complete response, and overall survival were not reached at the time of data cut-off. The most common treatment-emergent adverse events of any grade were CRS (83.3%), injection-site reactions (69.4%), infections (44.4%), neutropenia (38.9%), hypokalemia (27.8%), and decreased lymphocyte count (25.0%). Cytokine release syndrome occurrence was predictable; events were primarily low grade (grade 1–2), all resolved, and none led to treatment discontinuation. These encouraging results are consistent with previous findings and support the ongoing clinical evaluation of epcoritamab for the treatment of R/R DLBCL, including in earlier treatment lines.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"114 12","pages":"4643-4653"},"PeriodicalIF":5.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.15996","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysfunction of sinus macrophages in tumor-bearing host induces resistance to immunotherapy","authors":"Toshiki Anami,&nbsp;Cheng Pan,&nbsp;Yukio Fujiwara,&nbsp;Yoshihiro Komohara,&nbsp;Hiromu Yano,&nbsp;Yoichi Saito,&nbsp;Masamichi Sugimoto,&nbsp;Daiko Wakita,&nbsp;Takanobu Motoshima,&nbsp;Yoji Murakami,&nbsp;Junji Yatsuda,&nbsp;Naofumi Takahashi,&nbsp;Shinya Suzu,&nbsp;Kenichi Asano,&nbsp;Koji Tamada,&nbsp;Tomomi Kamba","doi":"10.1111/cas.16003","DOIUrl":"10.1111/cas.16003","url":null,"abstract":"<p>Sinus macrophages in draining lymph nodes (DLNs) are involved in anti-tumor immune reactions. CD169 (Sialoadhesin, Siglec-1) is expressed on sinus macrophages and is considered a surrogate marker for the immunostimulatory phenotype of macrophages. In this study, the significance of sinus macrophages in immunotherapy was evaluated using mouse models. Treatment with anti-programmed death-ligand 1 (PD-L1) antibody suppressed the subcutaneous tumor growth of MC38 and E0771 cells but was not effective against MB49 and LLC tumors. Decreased cytotoxic T-lymphocyte (CTL) infiltration in tumor tissues and CD169 expression in sinus macrophages were observed in MB49 and LLC cells compared to corresponding parameters in MC38 and E0771 cells. The anti-tumor effects of the anti-PD-L1 antibody on MC38 and E0771 cells were abolished when sinus macrophages in DLNs were depleted, suggesting that sinus macrophages are involved in the therapeutic effect of the anti-PD-L1 antibody. Naringin activated sinus macrophages. Naringin inhibited tumor growth in MB49- and LLC-bearing mice but did not affect that in MC38- and E0771-bearing mice. The infiltration of CTLs in tumor tissues and their activation were increased by naringin, and this effect was impaired when sinus macrophages were depleted. Combination therapy with naringin and anti-PD-L1 antibody suppressed MB49 tumor growth. In conclusion, CD169-positive sinus macrophages in DLNs are critical for anti-tumor immune responses, and naringin suppresses tumor growth by activating CD169-positive sinus macrophages and anti-tumor CTL responses. The activation status of sinus macrophages has been suggested to differ among tumor models, and this should be investigated in future studies.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"59-69"},"PeriodicalIF":5.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71487830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KDM4B: A promising oncology therapeutic target","authors":"Fangjing Ni,&nbsp;Heting Tang,&nbsp;Siteng Cheng,&nbsp;Yaoyu Yu,&nbsp;Zhihao Yuan,&nbsp;Yingfei Chen,&nbsp;Encheng Zhang,&nbsp;Xiang Wang","doi":"10.1111/cas.16005","DOIUrl":"10.1111/cas.16005","url":null,"abstract":"<p>Epigenetic modifications are significant in tumor pathogenesis, wherein the process of histone demethylation is indispensable for regulating gene transcription, apoptosis, DNA replication, and repair of damaged DNA. The lysine demethylases (KDMs) serve an essential role in the aforementioned processes, with particular emphasis on the KDM4 family, also referred to as JMJD2. Multiple studies have underscored the significance of the KDM4 family in the regulation of various biological processes including, but not limited to, the cell cycle, DNA repair mechanisms, signaling pathways, and the progression of tumor formation. Nevertheless, it is imperative to elucidate the underlying mechanism of KDM4B, which belongs to the <i>KDM4</i> gene family. This review presents a comprehensive examination of the structure, mechanism, and function of KDM4B, as well as a critical analysis of the current body of research pertaining to its involvement in tumorigenesis and development. Furthermore, this review explores the potential therapeutic strategies that specifically target KDM4B.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"8-16"},"PeriodicalIF":5.7,"publicationDate":"2023-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71487831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Suggested role for neutrophil extracellular trap formation in Ewing sarcoma immune microenvironment","authors":"Rachel Shukrun,&nbsp;Szilvia Baron,&nbsp;Victoria Fidel,&nbsp;Anna Shusterman,&nbsp;Osnat Sher,&nbsp;Netanya Kollender,&nbsp;Dror Levin,&nbsp;Yair Peled,&nbsp;Yair Gortzak,&nbsp;Yoav Ben-Shahar,&nbsp;Revital Caspi,&nbsp;Sagi Gordon,&nbsp;Michal Manisterski,&nbsp;Ronit Elhasid","doi":"10.1111/cas.15992","DOIUrl":"10.1111/cas.15992","url":null,"abstract":"<p>Ewing sarcoma (EWS) is a highly aggressive cancer with a survival rate of 70%–80% for patients with localized disease and under 30% for those with metastatic disease. Tumor-infiltrating neutrophils (TIN) can generate extracellular net-like DNA structures known as neutrophil extracellular traps (NETs). However, little is known about the presence and prognostic significance of tumor-infiltrating NETs in EWS. Herein, we investigated 46 patients diagnosed with EWS and treated in the Tel Aviv Medical Center between 2010 and 2021. TINs and NETs were identified in diagnostic biopsies of EWS by immunofluorescence. In addition, NETs were investigated in neutrophils isolated from peripheral blood samples of EWS patients at diagnosis and following neoadjuvant chemotherapy. The relationships between the presence of TINs and NETs, pathological and clinical features, and outcomes were analyzed. Our results demonstrate that TIN and NETs at diagnosis were higher in EWS patients with metastatic disease compared with those with local disease. High NET formation at diagnosis predicted poor response to neoadjuvant chemotherapy, relapse, and death from disease (<i>p</i> &lt; 0.05). NET formation in peripheral blood samples at diagnosis was significantly elevated among patients with EWS compared with pediatric controls and decreased significantly following neoadjuvant chemotherapy. In conclusion, NET formation seems to have a role in the EWS immune microenvironment. Their presence can refine risk stratification, predict chemotherapy resistance and survival, and serve as a therapeutic target in patients with EWS.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"115 1","pages":"36-47"},"PeriodicalIF":5.7,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10823276/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71428196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}