Cancer Science最新文献

{"title":"A Novel Method for Prognostic Risk Classification After Carbon-Ion Radiotherapy for Hepatocellular Carcinoma Using Data-Mining Methods","authors":"Kazuhiko Hayashi,&nbsp;Osamu Suzuki,&nbsp;Koji Ichise,&nbsp;Hirofumi Uchida,&nbsp;Makoto Anzai,&nbsp;Azusa Hasegawa,&nbsp;Shinichi Shimizu,&nbsp;Teruki Teshima,&nbsp;Jiro Fujimoto,&nbsp;Kazuhiko Ogawa","doi":"10.1111/cas.70079","DOIUrl":"10.1111/cas.70079","url":null,"abstract":"<p>No classification methods to predict prognosis after carbon-ion radiotherapy for hepatocellular carcinoma have yet been reported. This study aimed to develop risk classification for cancer-specific survival (CSS) after carbon-ion radiotherapy for hepatocellular carcinoma using decision tree analysis as a data-mining method. In this single-center, retrospective study, we analyzed 90 consecutive patients with hepatocellular carcinoma treated with carbon-ion radiotherapy between 2018 and 2022. Liver tumors were irradiated at 60 Gy (relative biological effectiveness [RBE]) in four fractions. If the tumor was close to the gastrointestinal tract, it was irradiated at 60 Gy [RBE] in 12 fractions. Univariate and multivariate analyses of progression-free survival (PFS) and CSS were performed to assess patients' background and treatment-related factors. Decision tree analysis (DTA) was performed to assess prognostic factors for CSS that were significantly different in the multivariate analysis. The median follow-up period was 32.8 months for all patients and 35.6 months for survivors. Multivariate analysis identified dose fractionation and pretreatment alpha-fetoprotein values as significant prognostic factors for PFS and CSS. Moreover, clinical stage and pretreatment protein induced by vitamin K absence or antagonist ΙΙ values were significant prognostic factors for CSS. DTA revealed that the patients could be divided into three groups according to prognosis: low-risk, high-risk, and intermediate-risk. Consequently, the 3-year CSS rates for the low-, intermediate-, and high-risk groups were 100%, 73.3%, and 44.4%, respectively. DTA represents a new method for risk classification for CSS after carbon-ion radiotherapy for hepatocellular carcinoma based on tumor markers and clinical stage.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2198-2207"},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70079","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144110","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":"TGF-β Enhances Doxorubicin Resistance and Anchorage-Independent Growth in Cancer Cells by Inducing ALDH1A1 Expression","authors":"Takashi Yokoyama,&nbsp;Masao Saitoh,&nbsp;Keiji Miyazawa","doi":"10.1111/cas.70109","DOIUrl":"10.1111/cas.70109","url":null,"abstract":"<p>The transforming growth factor-β (TGF-β)/Smad signaling pathway promotes malignant transformation through various mechanisms, and its effect on enhancing drug resistance can limit the efficacy of treatment. Here, we showed that pre-stimulation of human lung cancer A549 cells with TGF-β increases resistance to doxorubicin-induced growth inhibition in a Smad3- and Smad4-dependent manner. This effect was suppressed by the aldehyde dehydrogenase (ALDH) inhibitor oxyfedrine, suggesting that ALDH family members are involved in drug resistance. TGF-β upregulated the mRNA and protein expression of ALDH1A1. The TGF-β/Smad3 transcriptional enhancer region on <i>ALDH1A1</i> was identified by Smad3 ChIP-seq analysis using an open database and by reporter assays. Knockdown of <i>ALDH1A1</i> in A549 cells suppressed TGF-β–induced doxorubicin resistance, and lentivirus-mediated introduction of <i>ALDH1A1</i> into A549 <i>SMAD3</i>-KO cells restored drug resistance. We also demonstrated that ALDH1A1 is required and sufficient for TGF-β/Smad3 signaling–induced anchorage-independent growth. The results suggest that the TGF-β/Smad3/4 axis promotes resistance to doxorubicin and anchorage-independent growth by inducing the transcription of <i>ALDH1A1</i>.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2176-2188"},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144113","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":"KEYNOTE-A17: First-Line Pembrolizumab Plus Cisplatin–Pemetrexed in Japanese Participants With Advanced Pleural Mesothelioma","authors":"Takashi Kijima,&nbsp;Terufumi Kato,&nbsp;Yasushi Goto,&nbsp;Kozo Kuribayashi,&nbsp;Koji Mikami,&nbsp;Yoshiki Negi,&nbsp;Shuji Murakami,&nbsp;Tatsuya Yoshida,&nbsp;Masae Homma,&nbsp;Akira Wakana,&nbsp;Kazuo Noguchi,&nbsp;Nobukazu Fujimoto","doi":"10.1111/cas.70082","DOIUrl":"10.1111/cas.70082","url":null,"abstract":"<p>Pleural mesothelioma (PM) is an inflammatory cancer linked with asbestos exposure and has a poor prognosis. We report results of the phase 1b KEYNOTE-A17 study (NCT04153565) of first-line pembrolizumab plus chemotherapy in Japanese participants with advanced PM. Participants aged ≥ 20 years with previously untreated, histologically confirmed advanced or unresectable PM received pembrolizumab 200 mg every 3 weeks (Q3W) for ≤ 35 cycles with cisplatin 75 mg/m² and pemetrexed 500 mg/m² Q3W for 4–6 cycles. Primary endpoints were the rate of dose-limiting toxicities (DLTs), adverse events (AEs), and treatment discontinuations due to AEs. DLTs were assessed during cycle 1 in 18 participants, and having ≤ 8 participants with DLTs was considered tolerable. AEs were graded per NCI CTCAE 5.0. Tumor response was evaluated per modified RECIST for PM by the investigator. Among 19 participants enrolled, the median study follow-up was 30.8 (range, 27.8–33.3) months (data cutoff September 21, 2022). Of 18 participants evaluated for DLTs, 2 (11%) experienced 4 DLTs (hypoalbuminemia, malaise, pyrexia in 1 participant; uveitis in 1 participant). 18/19 participants (95%) experienced treatment-related AEs; 14 (74%) had grade 3–4 events (no grade 5). Treatment-related AEs led to discontinuation of any drug in 5 participants (26%). The objective response rate was 74% (partial response, <i>n</i> = 14), and the median (range) duration of response was 16.8 (3.0–26.3+) months. First-line pembrolizumab plus chemotherapy was tolerable based on the low incidence of DLTs and showed acceptable safety and preliminary antitumor activity in Japanese participants with advanced PM.</p><p><b>Trial Registration:</b> NCT04153565</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2208-2217"},"PeriodicalIF":4.3,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70082","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129074","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":"The Pro-Apoptotic Effect of Glucose Restriction in NSCLC via AMPK-Regulated Circadian Clock Gene Bmal1","authors":"Tao Wei,&nbsp;Ying Cheng,&nbsp;Jierong Ge,&nbsp;Manting Zhu,&nbsp;Hong Chen,&nbsp;Qing Feng","doi":"10.1111/cas.70098","DOIUrl":"10.1111/cas.70098","url":null,"abstract":"<p>The circadian clock is a crucial regulator of mammalian physiology, controlling daily oscillations in key biological processes, such as cell proliferation, apoptosis, and DNA damage repair. Disruption of circadian rhythms has been identified as a significant risk factor for cancer development and progression, yet the specific molecular mechanisms linking circadian dysfunction to cancer remain poorly understood. Recent studies have increasingly focused on the role of diet in modulating circadian rhythms, highlighting the potential for dietary interventions in cancer management. However, how dietary factors like glucose restriction interact with circadian rhythms to influence cancer cell behavior remains an open question. Here, we investigate the mechanisms underlying glucose restriction-induced apoptosis in non-small cell lung cancer (NSCLC) cells, with a focus on the role of circadian clock genes. Analysis of the GEPIA database revealed that the circadian gene Bmal1 is highly expressed in normal tissues and associated with better prognosis in lung adenocarcinoma patients. In NSCLC cells, Bmal1 expression correlated with proapoptotic gene activity. In a tumor xenograft model using severe combined immunodeficiency (SCID) mice, a glucose-restricted (ketogenic) diet significantly delayed tumor growth and increased the expression of Bmal1 and proapoptotic genes. These findings suggest that glucose restriction promotes apoptosis in NSCLC cells through a Bmal1-mediated pathway, providing novel insights into the intersection between circadian regulation and cancer biology. Targeting core circadian clock genes like Bmal1 may represent a promising therapeutic strategy for managing lung cancer, broadening our understanding of how circadian rhythms can be harnessed for cancer prevention and treatment.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2101-2112"},"PeriodicalIF":4.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144112045","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 by a Humanized Cancer-Specific Anti-Podoplanin Monoclonal Antibody humPMab-117 Against Human Tumors","authors":"Tomohiro Tanaka,&nbsp;Hiroyuki Suzuki,&nbsp;Tomokazu Ohishi,&nbsp;Manabu Kawada,&nbsp;Mika K. Kaneko,&nbsp;Yukinari Kato","doi":"10.1111/cas.70103","DOIUrl":"10.1111/cas.70103","url":null,"abstract":"<p>Podoplanin (PDPN), also referred to as T1α/Aggrus, is a type I transmembrane sialoglycoprotein that plays a crucial role in invasiveness, stemness, and epithelial-to-mesenchymal transition, all of which contribute to the malignant progression of tumors. Therefore, a monoclonal antibody (mAb) against PDPN has been evaluated in preclinical models as a promising tumor therapy strategy. However, PDPN plays an essential role in normal development, such as in the development of the lungs. On-target toxicity by anti-PDPN mAbs to normal cells should be avoided to minimize adverse effects. A cancer-specific mAb against PDPN, PMab-117 (rat IgM, kappa), was previously established. This study engineered the humanized IgG₁ version (humPMab-117) to investigate antitumor activity. Flow cytometry analysis confirmed that humPMab-117 recognized PDPN-overexpressed glioma LN229 (LN229/PDPN) cells as well as PDPN-positive PC-10 (human lung squamous cell carcinoma) and LN319 (human glioblastoma) cells. In contrast, humPMab-117 did not react with normal epithelial cells from the lung bronchus, gingiva, mammary gland, corneal, and normal kidney podocytes, suggesting that humPMab-117 retains cancer-specific reactivity. Furthermore, humPMab-117 effectively induced antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity against LN229/PDPN, PC-10, and LN319 cells. In the xenograft tumor models, humPMab-117 demonstrated strong antitumor efficacy. These results suggest the potential of humPMab-117 as a therapeutic antibody for treating PDPN-positive malignant tumors.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2232-2242"},"PeriodicalIF":4.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70103","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111746","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":"CXCL13 and CCL21 Induce Tertiary Lymphoid Structures and Enhance the Efficacy of Immunotherapy for Melanoma","authors":"Maki Yoshimitsu,&nbsp;Motoki Nakamura,&nbsp;Shinji Kano,&nbsp;Tetsuya Magara,&nbsp;Hiroshi Kato,&nbsp;Aiko Sakai,&nbsp;Masaya Sugiyama,&nbsp;Masashi Mizokami,&nbsp;Akimichi Morita","doi":"10.1111/cas.70105","DOIUrl":"10.1111/cas.70105","url":null,"abstract":"<p>Tertiary lymphoid structures (TLS) are acquired ectopic lymph follicle-like structures observed inside and around tumors, in which clusters of CD20-positive B lymphocytes are surrounded by CD3-positive T lymphocytes. In many cancers, the existence of TLS is a useful biomarker for better prognosis and better response to immune checkpoint inhibitors (ICI) and plays important roles in activating anti-tumor immunity. In order to induce TLS and enhance the therapeutic effect of ICI, we attempted to induce TLS using multiple chemokines in malignant melanoma, for which there have been no reports of TLS induction previously. Immunohistochemical analysis of tumor samples from 41 melanoma patients treated with ICI revealed TLS in 63.4% of cases. Patients with ≥ 5 TLS exhibited significantly improved disease-specific survival compared to those with fewer or no TLS. Plasma chemokine profiling in 46 samples from 18 melanoma patients showed elevated CC motif chemokine ligand 21 (CCL21) in TLS-positive samples before and after ICI treatment and CXC motif chemokine ligand 13 (CXCL13) significantly increased pre- to post-ICI treatment in paired samples from TLS-positive patients. In a mouse melanoma model, co-administration of CXCL13 and CCL21 alongside anti-programmed death ligand-1 (PD-L1) antibody therapy significantly increased TLS formation and improved tumor growth suppression. Gene expression analysis of human melanoma samples demonstrated that high CXCL13 and CCL21 expression correlated with upregulation of immune response, particularly B cell activation. These findings highlight the potential of chemokine-based therapies. TLS induction using CXCL13 and CCL21 in combination may be useful for enhancing the effects of ICI therapy in melanoma.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2075-2085"},"PeriodicalIF":4.3,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70105","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144111769","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":"Clonal Hematopoiesis and Solid Cancers","authors":"Yen T. M. Nguyen,&nbsp;Manabu Fujisawa,&nbsp;Shumpei Ishikawa,&nbsp;Mamiko Sakata-Yanagimoto","doi":"10.1111/cas.70097","DOIUrl":"10.1111/cas.70097","url":null,"abstract":"<p>Clonal hematopoiesis refers to the expansion of hematopoietic stem cells harboring somatic mutations, a phenomenon increasingly recognized in aging populations. This review highlights the emerging relationship between clonal hematopoiesis and solid cancers, focusing on the prevalence and impact of clonal hematopoiesis–associated mutations such as <i>DNMT3A</i>, <i>TET2</i>, <i>ASXL1</i>, and <i>TP53</i> in tumorigenesis. Key risk factors for the co-occurrence of clonal hematopoiesis and solid cancers, including germline genetic factors, aging, and environmental factors, are also discussed. We explore how clonal hematopoiesis mutations shape the tumor microenvironments in solid cancers by modulating immunoregulation, inflammation, and angiogenesis, thereby contributing to tumor progression. These findings underscore the dual role of clonal hematopoiesis as both a marker of cancer risk and a potential driver of solid cancer progression. The clinical implications of clonal hematopoiesis are also considered, including the prognostic value, impact on treatment response, and potential as a therapeutic target. Future directions are outlined to advance our understanding of clonal hematopoiesis and to exploit its clinical potential for cancer management.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2055-2063"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095451","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":"Hypoxia Inhibitor Improves Iodine Uptake Disorder in Thyroid Cancer Through the hsa_circ_0023990/miR-448/DNMT1/NIS Axis","authors":"Ruiqin Gou,&nbsp;Shiqi Chen,&nbsp;Yangyang Lei,&nbsp;Pengqing Wu,&nbsp;Xuezhong Chen,&nbsp;Qing Zhang","doi":"10.1111/cas.70102","DOIUrl":"10.1111/cas.70102","url":null,"abstract":"<p>This research seeks to investigate how hypoxia inhibitors enhance iodine uptake in thyroid cancer cells. Clinical samples were gathered and assessed for hsa_circ_0023990, DNMT1, NIS, and their promoter methylation levels using RT-PCR, western blot, and methylation-specific PCR (MSP) techniques. The study involved examining the impact and mechanism of hsa_circ_0023990 on iodine uptake in differentiated thyroid carcinoma (DTC) cells through genetic manipulation. Luciferase reporter gene experiments were conducted to validate the interaction between hsa_circ_0023990, DNMT1, and miR-448. Xenograft tumors were established in nude mice for in vivo validation. The results showed that hsa_circ_0023990 was notably elevated in DTC and RAIR-DTC tissues. It was found that hsa_circ_0023990 could modulate NIS promoter methylation via the miR-448/DNMT1 signaling pathway, thereby influencing NIS expression. Hypoxia inhibitors effectively suppressed hsa_circ_0023990 expression in DTC cells, leading to increased NIS expression and enhanced iodine uptake. Subcutaneous transplantation experiments in animals further confirmed that hypoxia inhibitors could boost iodine absorption in tumor tissue and inhibit tumor growth through the hsa_circ_0023990/miR-448/DNMT1/NIS signaling axis. In conclusion, hypoxia inhibitors ameliorate iodine uptake dysfunction in thyroid cancer by acting on the hsa_circ_0023990/miR-448/DNMT1/NIS signaling pathway.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2113-2124"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70102","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095546","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":"Ligand-Based CAR-T Cells Targeting EGFR Exhibit Favorable Antitumor Effects Against Gynecologic Malignancies","authors":"Manaka Shinagawa,&nbsp;Koichi Hirabayashi,&nbsp;Marina Fujioka,&nbsp;Kyosuke Kamijo,&nbsp;Natsuki Uchiyama,&nbsp;Yusuke Yokokawa,&nbsp;Yasuhiro Tanaka,&nbsp;Motoki Ono,&nbsp;Thanyavi Chinsuwan,&nbsp;Ryoichi Asaka,&nbsp;Aiko Hasegawa,&nbsp;Miyuki Tanaka,&nbsp;Takashi Murakami,&nbsp;Shigeki Yagyu,&nbsp;Tsutomu Miyamoto,&nbsp;Tanri Shiozawa,&nbsp;Yozo Nakazawa","doi":"10.1111/cas.70106","DOIUrl":"10.1111/cas.70106","url":null,"abstract":"<p>Epidermal growth factor receptor (EGFR) has been reported to be overexpressed in gynecologic malignancies. However, the clinical efficacy of existing molecular EGFR-targeted therapies against gynecologic malignancies has not been demonstrated. In this study, we investigated the antitumor effects of ligand-based EGFR chimeric antigen receptor (CAR)-T cells on gynecologic malignancies. First, we evaluated EGFR expression in patient samples using immunohistochemistry. EGFR positivity was observed in 41%, 82%, and 79% of ovarian, endometrial, and cervical cancer in patient samples, respectively. Second, we generated ligand-based EGFR CAR-T cells via <i>piggyBac</i>-mediated gene transfer. EGFR CAR-T cells were successfully generated with high CAR positivity and a high proportion of naïve/stem cell memory-like T cells. Finally, we investigated the antitumor effects of EGFR CAR-T cells on gynecologic malignancies. EGFR CAR-T cells were co-cultured with six EGFR-positive gynecologic cancer cell lines. The growth of all six gynecologic cancer cell lines was significantly suppressed by EGFR CAR-T cells compared to mock T cells. In in vivo studies, tumor-bearing mice implanted with gynecologic cancer cell lines in their intraperitoneal cavity were administered EGFR CAR-T cells, CD19 CAR-T cells, or PBS intraperitoneally. Mice treated with EGFR CAR-T cells displayed a significantly decreased tumor burden compared to those treated with either CD19 CAR-T cells or PBS. Additionally, mice treated with EGFR CAR-T cells had a significantly longer survival than the other groups. In summary, ligand-based EGFR CAR-T cells may be a promising therapy for various gynecologic malignancies.</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2243-2255"},"PeriodicalIF":4.3,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144095500","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":"PI3Kδ Inhibitor Parsaclisib in Japanese Patients With Relapsed or Refractory Follicular Lymphoma","authors":"Noriko Fukuhara,&nbsp;Isao Yoshida,&nbsp;Takuro Ishiguro,&nbsp;Katsuya Fujimoto,&nbsp;Junya Kuroda,&nbsp;Toshiki Uchida,&nbsp;Ryusuke Yamamoto,&nbsp;Yoshiaki Ogawa,&nbsp;Yasushi Hiramatsu,&nbsp;Toshiro Ito,&nbsp;Seiichiro Katagiri,&nbsp;Tomonori Nakazato,&nbsp;Kazumi Suzukawa,&nbsp;Kenzo Kinami,&nbsp;Mi Zhou,&nbsp;Eiju Negoro","doi":"10.1111/cas.70046","DOIUrl":"10.1111/cas.70046","url":null,"abstract":"<p>Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphoma (NHL) in Japan, the United States, and Western Europe. Parsaclisib is a potent, selective next-generation PI3Kδ inhibitor that has demonstrated clinical efficacy and tolerability in phase II studies of patients with relapsed or refractory (R/R) B-cell NHL, including FL. We report results from CITADEL-213 (NCT04434937), a phase II study evaluating the efficacy and safety of parsaclisib in Japanese patients with R/R FL. Eligible patients were aged ≥ 18 years with histologically confirmed R/R FL (grade 1, 2, or 3a), had received two or more prior systemic therapies, and were ineligible for hematopoietic stem cell transplantation. Patients received parsaclisib 20 mg once daily for 8 weeks, followed by parsaclisib 2.5 mg once daily thereafter. The primary endpoint was the objective response rate (ORR). At the data cut-off (February 16, 2023), 42 patients had received treatment with parsaclisib, of whom 41 were evaluable for change in target tumor size. Median (range) age at baseline was 66.5 (52–87) years. ORR (95% confidence interval [CI]) was 88.1% (74.4–96.0), with 10 patients (23.8%) experiencing a complete response and 27 patients (64.3%) experiencing a partial response. Median (95% CI) duration of response was not reached (8.0 months−not estimable). The most common treatment-emergent adverse events (TEAEs) were diarrhea (28.6%; grade ≥ 3, 7.1%) and stomatitis (23.8%; grade ≥ 3, 11.9%); TEAEs led to parsaclisib discontinuation in five patients (11.9%). There were no fatal TEAEs. In conclusion, parsaclisib monotherapy demonstrated durable responses with a manageable safety profile in Japanese patients with R/R FL.</p><p><b>Trial Registration:</b> ClinicalTrials.gov, NCT04434937</p>","PeriodicalId":9580,"journal":{"name":"Cancer Science","volume":"116 8","pages":"2189-2197"},"PeriodicalIF":4.3,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/cas.70046","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144038801","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}