Cancer Medicine最新文献

{"title":"Clinical Presentation and Long-Term Survival Outcomes of Patients With Monoclonal Gammopathy of Renal Significance (MGRS): A Multicenter Retrospective Study","authors":"K. Mancuso,&nbsp;R. Mina,&nbsp;S. Rocchi,&nbsp;E. Antonioli,&nbsp;M. T. Petrucci,&nbsp;F. Fazio,&nbsp;A. Gozzetti,&nbsp;M. Salvini,&nbsp;C. S. Cartia,&nbsp;G. Bertuglia,&nbsp;F. Patriarca,&nbsp;A. B. Dalla Palma,&nbsp;S. Barbato,&nbsp;G. De Cicco,&nbsp;F. Bigi,&nbsp;E. Favero,&nbsp;P. Tacchetti,&nbsp;L. Pantani,&nbsp;I. Rizzello,&nbsp;M. Puppi,&nbsp;M. Talarico,&nbsp;V. Solli,&nbsp;A. Kanapari,&nbsp;M. Cavo,&nbsp;E. Zamagni","doi":"10.1002/cam4.70266","DOIUrl":"10.1002/cam4.70266","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>MGRS are new rare clinical entities, whose recognition and optimal management is evolving.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>To implement real-life data, we retrospectively analysed a multicentre cohort of 60 patients with renal biopsy-proven MGRS receiving mainly novel treatments (between 2006 and 2021) in eight Italian centres. Based on renal biopsy, patients were divided into two subgroups: AL amyloidosis (70%, <i>n</i> = 42) and other-MGRS (30%, <i>n</i> = 18).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Baseline characteristics follow typical manifestations of MGRS disorders in terms of small clonal burden, laboratory and clinical features. More patients with AL amyloidosis had monotypic lambda light-chain disease, estimated glomerular filtration rate (eGFR) ≥ 60 mL/min and nephrotic proteinuria than other-MGRS group. The most widely used drug was bortezomib, and about one-third of patients underwent ASCT. Overall response rate was 86% with no differences in the two subgroups. However, high-quality hematologic responses ≥very good partial response (VGPR) were greater in AL amyloidosis than in other-MGRS group (67% vs 28%, <i>p</i> = 0.015). The depth of haematological response influenced renal response, obtained in 32 (59%) of evaluable patients, similarly in the subgroups. Indeed, 75% patients with ≥ VGPR (<i>p</i> = 0.049) and none with stable disease (<i>p</i> ≤ 0.001) obtained a renal response. No association between renal response and histotypes (<i>p</i> = 0.9) or type of first-line therapy (<i>p</i> = 0.3) was found. At a median follow-up of 54.4 months (IQR 24.8–102.8), median progression-free survival (PFS) was 100.1 months (95% CI 34.9–NR), and median overall survival not reached (95% CI 129.8–NR). No significant difference emerged between the two groups in terms of survival outcomes. Achieving ≥ VGPR was confirmed as the main independent predictor of prolonged PFS in the general population (HR = 0.29, <i>p</i> = 0.023) and AL amyloidosis group (HR 0.23; <i>p</i> = 0.023). Preserved renal function at diagnosis was predictive of improved PFS in the AL amyloidosis group (eGFR ≥ 60 mL/min: HR = 0.003; <i>p</i> = 0.018; eGFR 30–60 mL/min: HR = 0.04, <i>p</i> = 0.046).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Further research is warranted to develop standardised response criteria and treatment strategies to improve MGRS management.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714929","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":"Fusobacterium nucleatum Abundance is Associated with Cachexia in Colorectal Cancer Patients: The ColoCare Study","authors":"Mmadili N. Ilozumba,&nbsp;Tengda Lin,&nbsp;Sheetal Hardikar,&nbsp;Doratha A. Byrd,&nbsp;June L. Round,&nbsp;W. Zac Stephens,&nbsp;Andreana N. Holowatyj,&nbsp;Christy A. Warby,&nbsp;Victoria Damerell,&nbsp;Christopher I. Li,&nbsp;Jane C. Figueiredo,&nbsp;Adetunji T. Toriola,&nbsp;David Shibata,&nbsp;Gary C. Fillmore,&nbsp;Bartley Pickron,&nbsp;Erin M. Siegel,&nbsp;Christoph Kahlert,&nbsp;Vaia Florou,&nbsp;Biljana Gigic,&nbsp;Jennifer Ose,&nbsp;Cornelia M. Ulrich","doi":"10.1002/cam4.70431","DOIUrl":"10.1002/cam4.70431","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Cachexia accounts for about 20% of all cancer-related deaths and indicates poor prognosis. The impact of <i>Fusobacterium nucleatum (Fn</i>), a microbial risk factor for colorectal cancer (CRC), on the development of cachexia in CRC has not been established.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We evaluated the association between <i>Fn</i> abundance in pre-surgical stool samples and onset of cachexia at 6 months post-surgery in <i>n</i> = 87 patients with stages I–III CRC in the ColoCare Study.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>High fecal <i>Fn</i> abundance compared to negative/low fecal <i>Fn</i> abundance was associated with 4-fold increased risk of cachexia onset at 6 months post-surgery (OR = 4.82, 95% CI = 1.15, 20.10, <i>p</i> = 0.03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our findings suggest that high fecal <i>Fn</i> abundance was associated with an increased risk of cachexia at 6 months post-surgery in CRC patients. This is the first study to link <i>Fn</i> abundance with cachexia in CRC patients, offering novel insights into biological mechanisms and potential management of cancer cachexia. Due to the small sample size, our results should be interpreted with caution. Future studies with larger sample sizes are needed to validate these findings.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70431","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714935","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":"Microbiome-Based Colon Cancer Patient Stratification and Survival Analysis","authors":"Joshua Smyth,&nbsp;Julien Godet,&nbsp;Anisa Choudhary,&nbsp;Anubrata Das,&nbsp;Georgios V. Gkoutos,&nbsp;Animesh Acharjee","doi":"10.1002/cam4.70434","DOIUrl":"10.1002/cam4.70434","url":null,"abstract":"<div>\u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) is any cancer that starts in the colon or the rectum and presents a significant health concern. It is the third most diagnosed and the second deadliest cancer, with an estimated 153,020 new cases and 52,550 deaths in 2023. The severity of colon cancer may be attributed to its ability to avoid the host immune system and growth suppressors, its asymptomatic nature in the early stages, its association with a continually ageing population and unfavourable diet and obesity. The composition of the gut microbiome plays an important role in the development of CRC and presents as an important target in early detection and in predicting treatment outcomes in CRC. This study aims to identify microbiome-specific derived clusters in CRC patients and conduct subsequent survival analysis using the specific microbiome features within clusters.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Consensus clustering and feature selection, involving a Kruskal–Wallis test, a random forest and least absolute shrinkage and selection operator (LASSO) were applied resulting in the identification of differently expressed microbiomes between clusters. Lastly, survival analysis was performed on the selected features using Kaplan-Meier curves and Cox regression. <i>K</i>-means clustering, as selected using consensus clustering interpretation, presented three distinct clusters with clear differences in alpha and beta diversity and baseline clinical variables.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total 1311 of the 1406 microbes were selected using the Kruskal Wallis and passed to the random forest and LASSO, which narrowed the dataset to 140 features. Following the survival analysis, eight microbiome species, namely <i>N4likevirus, Ambidensovirus, Synechococcus, Thermithiobacillus, Hydrocarboniphaga, Rhodovibrio, Gloeobacter</i> and <i>Candidatus Nitrosotenuis,</i> were selected as significant in clustering and survival.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study reveals the heterogeneity of the CRC microbiome and its effect on disease prognosis and necessitates further exploration of the biological mechanisms of these selected microbiomes as well further investigation of whether the approach depicted here is applicable to other cancer types.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70434","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680267","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":"Hypothalamic–Pituitary–Adrenal Axis Dysfunction in People With Cancer: A Systematic Review","authors":"Natalie G. Kanter,&nbsp;Sarah Cohen-Woods,&nbsp;David A. Balfour,&nbsp;Morton G. Burt,&nbsp;Alison L. Waterman,&nbsp;Bogda Koczwara","doi":"10.1002/cam4.70366","DOIUrl":"10.1002/cam4.70366","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Purpose</h3>\u0000 \u0000 <p>Cancer can be a source of significant psychological and physical stress. Prolonged stressful stimuli can influence the stress response, mediated by the hypothalamic–pituitary–adrenal (HPA) axis. However, there is limited literature investigating HPA axis function in patients with cancer.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A systematic literature review of case–control studies was conducted comparing individuals with and without cancer examining the HPA axis function. Databases (MEDLINE, PubMed, Scopus) were searched from inception to May 2023.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Seventeen studies met eligibility criteria: nine unstimulated-cortisol studies and eight reporting the effect of HPA stimulation or suppression. Sixteen studies reported altered levels of HPA function in cancer patients relative to controls, including 13 reporting increased baseline or hyperactive cortisol responses, and four—decreased baseline cortisol or blunted cortisol responses, two of which had patient groups with now known cortisol-suppressing treatments. HPA dysfunction was observed in patients of both sexes, diverse ages, stages of cancer and cancer treatments. Six papers reported on clinical outcomes with cases experiencing higher levels of fatigue, stress, poor memory, poor well-being and disturbed sleep. There was significant heterogeneity in methodologies across the studies.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HPA dysfunction was common in patients with cancer relative to cancer-free controls. The majority of studies in cancer reported an increased baseline cortisol and increased response to HPA stimulation. There is a need for well-powered studies using standardised methodology examining the mechanisms of HPA dysregulation and their health outcomes, to enable the development of appropriate tools for the diagnosis and management of HPA dysfunction in cancer.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70366","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680263","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":"Patients Can Administer Mobile Audio Recordings to Increase Knowledge in Advanced Prostate Cancer","authors":"Daniel H. Kwon,&nbsp;Lauren Trihy,&nbsp;Nika Darvish,&nbsp;Eliza Hearst,&nbsp;Saffanat Sumra,&nbsp;Hala T. Borno,&nbsp;Rohit Bose,&nbsp;Jonathan Chou,&nbsp;Ivan de Kouchkovsky,&nbsp;Arpita Desai,&nbsp;Brad Ekstrand,&nbsp;Terence Friedlander,&nbsp;Gurleen Kaur,&nbsp;Vadim S. Koshkin,&nbsp;Samantha Nesheiwat,&nbsp;Karen Sepucha,&nbsp;Eric J. Small,&nbsp;Rahul R. Aggarwal,&nbsp;Jeffrey Belkora","doi":"10.1002/cam4.70433","DOIUrl":"10.1002/cam4.70433","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Introduction&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Consultation audio recordings improve patient decision-making but are underutilized. Patient-administered recording apps on mobile devices may increase access, but implementation has not been evaluated.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;We conducted a single-arm study delivering education, coaching, and reminders for patients to record their appointment using a mobile recording app. Patients had progressive, advanced prostate cancer and an upcoming appointment where the option of docetaxel would be discussed. We used the RE-AIM framework for evaluation. Reach was the proportion of patients who participated. Effectiveness was change in informed decision-making pre- vs. post-appointment. We used a questionnaire evaluating patient knowledge about docetaxel (0%–100% correct) and the decisional conflict scale-informed subscale (0 = feels extremely uninformed to 100 = extremely informed) to compare means using the paired &lt;i&gt;t&lt;/i&gt;-test. Adoption was the proportion of providers agreeing to be recorded. Implementation was coordinator adherence to intervention delivery. We conducted semistructured interviews with patients, caregivers, and providers to assess barriers, facilitators, and suggestions for recording implementation.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Of 102 patients approached, 50 (49%) patients participated. Mean age was 75 years, 38 (76%) were Non-Hispanic White, and 43 (86%) had telehealth appointments. Knowledge increased from 44.7% to 49.5% (&lt;i&gt;p&lt;/i&gt; = 0.019), particularly about palliative care (42% answering correctly to 60%, &lt;i&gt;p&lt;/i&gt; = 0.035). Decisional conflict-informed subscale increased from 48.9 to 70.9 (&lt;i&gt;p&lt;/i&gt; &lt; 0.001). Forty-three patients (85%) made a recording, of whom 33 (77%) reported the recording helped treatment decision-making. All 17 providers agreed to be recorded. Coordinator adherence was high. Multi-level barriers, suggestions, and facilitators mostly related to intervention complexity and stakeholder compatibility.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Patient-administered audio recordings had a positive effect on decision-making, particularly for palliative care awareness. For broader implementation, efforts should focus on revising institutional policies; teaching patients or caregivers to use existing recording functions on their devices; leveraging artificial intelligence for transcription and summarization; and integrating recording into telehealth technology and electronic patient portals.&lt;/p&gt;\u0000 \u0000 &lt;p&gt;&lt;b&gt;Tria","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70433","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680269","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":"MTHFD1 Regulates Autophagy to Promote Growth and Metastasis in Colorectal Cancer via the PI3K-AKT–mTOR Signaling Pathway","authors":"Zhihao Li,&nbsp;Haoxian Ke,&nbsp;Jiawei Cai,&nbsp;Shubiao Ye,&nbsp;Junfeng Huang,&nbsp;Chi Zhang,&nbsp;Ming Yuan,&nbsp;Ping Lan,&nbsp;Xianrui Wu","doi":"10.1002/cam4.70267","DOIUrl":"10.1002/cam4.70267","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>Methylenetetrahydrofolate dehydrogenase 1 (MTHFD1) is the enzyme with the activities of methylenetetrahydrofolate dehydrogenase, methylenetetrahydrofolate cyclohydrolase, and formyltetrahydrofolate synthetase. Our aim was to elucidate the function of MTHFD1 in colorectal cancer (CRC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In vitro assessments of the proliferation, invasion, and migration abilities of CRC cells were conducted using Immunohistochemistry, Transwell invasion assays, Western blot (WB), and Cell counting Kit-8 assays. WB was also utilized to measure autophagy protein levels and PI3K-AKT-mTOR signaling pathway expression. Furthermore, the role of MTHFD1 was evaluated in vivo by using subcutaneous xenograft tumor models and lateral tail vein metastasis models of human CRC in nude mice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overexpression of MTHFD1 promoted the abilities of tumorigenesis and metastasis in CRC in vitro and in vivo and reduced autophagy, attributing to the PI3K-AKT-mTOR signaling pathway in CRC cells. In contrast, the down-regulation of MTHFD1 increased autophagy and suppressed their proliferation, migration, and invasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>MTHFD1 can modulate the PI3K-AKT-mTOR signaling pathway to suppress autophagy and stimulate tumorigenesis and metastasis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70267","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685550","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":"Genetic Characteristics of Cutaneous, Acral, and Mucosal Melanoma in Japan","authors":"Tokimasa Hida,&nbsp;Masashi Idogawa,&nbsp;Junji Kato,&nbsp;Yukiko Kiniwa,&nbsp;Kohei Horimoto,&nbsp;Sayuri Sato,&nbsp;Masahide Sawada,&nbsp;Shoichiro Tange,&nbsp;Masae Okura,&nbsp;Ryuhei Okuyama,&nbsp;Takashi Tokino,&nbsp;Hisashi Uhara","doi":"10.1002/cam4.70360","DOIUrl":"https://doi.org/10.1002/cam4.70360","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Acral and mucosal melanomas are more prevalent in Asians than in Caucasians, unlike cutaneous melanomas, which are predominant in Caucasians. Recent studies have suggested that non-Caucasian cutaneous melanomas responded less to immune checkpoint inhibitors, highlighting the need for genetic profiling across ethnicities. This study aimed to elucidate the genetic characteristics of Japanese melanomas, which is an under-researched topic.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Single-nucleotide variants, indels, and copy number alterations in 104 Japanese melanoma patients (37 cutaneous, 52 acral, and 15 mucosal) were analyzed using custom panel sequencing.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Driver events were detected in 94% of the cases. Among cutaneous melanoma cases, 76% had BRAF mutations, and 8% had NRAS mutations. In acral melanoma, BRAF (9%), NRAS (17%), KRAS (8%), KIT (19%), and NF1 (7%) mutations were detected. Major driver mutations in mucosal melanoma were detected in NRAS, KRAS, NF1, PTEN, GNAQ, and KIT. The median tumor mutational burden across all melanoma types was 4.6 mutations/Mb, with no significant difference between the cutaneous and acral/mucosal types. Of the 21 patients with both primary and metastatic lesions, 11 showed distinct mutations in each. Potentially actionable mutations were detected in 58 patients in addition to BRAF V600E/K mutations in 31.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>This study highlights distinct genetic abnormalities and actionable alterations in Japanese melanoma patients. This suggests a lower tumor mutational burden in East Asian cutaneous melanoma, which may affect the efficacy of immune checkpoint inhibitors. The heterogeneity of driver mutations across and within individuals highlights the need for personalized treatment approaches.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70360","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674079","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":"Epigenetic and Immune Profile Characteristics in Sinonasal Undifferentiated Carcinoma","authors":"Hyang Joo Ryu,&nbsp;Chung Lee,&nbsp;Sun Och Yoon","doi":"10.1002/cam4.70413","DOIUrl":"https://doi.org/10.1002/cam4.70413","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Introduction</h3>\u0000 \u0000 <p>Sinonasal undifferentiated carcinoma (SNUC) is a rare and highly aggressive malignancy originating in the nasal cavity and paranasal sinuses. Its pathogenesis and immune characteristics remain poorly understood.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objectives</h3>\u0000 \u0000 <p>This study investigates the molecular aspects of SNUC, focusing on tumorigenesis and immunity.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>For this purpose, spatial transcriptome analysis was employed to compare the gene expression profiles of SNUC tumor cells with those of normal epithelial cells, as well as to compare tumor-infiltrating immune cells with immune cells from normal, tumor-free tissue areas. For validation, next-generation sequencing tests and clinical sample studies were conducted.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Spatial transcriptome analysis revealed notable upregulation of EZH2 and the histone family gene such as H3C2 (H3-clustered histone 2) in SNUC tumor cells. Additionally, gene set enrichment analysis identified significant activations in the histone deacetylase (HDAC) signaling pathway, histone acetyltransferase (HAT) pathway, polycomb repressive complex 2 (PRC2), and DNA methylation pathways. A notable decrease was observed in downregulated genes and pathways, including the mucin family of protein genes, the keratin protein gene, and the mucin glycosylation pathway. Next-generation sequencing did not reveal specific genetic mutations within these pathways, although mutations such as <i>IDH2 R172S</i> were noted. Clinical SNUC tissues confirmed increased immunoexpression of EZH2 and PRC2 markers. Analysis of tumor immunity revealed a characteristic immune cell signature, with a notable predominance of naïve B cells, macrophages, CD8 memory T cells, and Tregs in the SNUC microenvironment, alongside the increased expression of LAG3 in tumor-infiltrating immune cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Our study suggests epigenetic mechanisms, particularly via EZH2, play a crucial role in SNUC carcinogenesis. Furthermore, distinctive immune cell profiles in SNUC point to potential immune-related characteristics of this malignancy.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70413","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674080","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":"Phase I study of BC001, a novel fully human immunoglobulin G1 monoclonal antibody targeting the vascular endothelial growth factor receptor-2, in advanced solid tumors","authors":"Dan Liu,&nbsp;Jifang Gong,&nbsp;Muling Liu,&nbsp;Huan Zhou,&nbsp;Shumei Wang,&nbsp;Jian Yang,&nbsp;Chenwei Shang,&nbsp;Xinlei Guo,&nbsp;Cha Wang,&nbsp;Yanqiao Zhang,&nbsp;Lin Shen","doi":"10.1002/cam4.70208","DOIUrl":"https://doi.org/10.1002/cam4.70208","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>BC001 is a novel fully human immunoglobulin G1 monoclonal antibody blocking VEGFR2. This phase I study aimed to assess BC001 alone and plus chemotherapy in solid tumors.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In dose escalation part, BC001 was assessed at dose levels of 2, 4, 8, 12, 16 mg/kg on day 1,15, every 28 days, followed an accelerated titration and “3 + 3” design. BC001 plus paclitaxel was assessed at dose level of 8, 10 mg/kg. The primary endpoints included the DLT, MTD and RDE of BC001. In dose expansion part, it aimed to assess the anti-tumor activity of BC001 alone and plus chemotherapy in gastric cancer as 2nd line treatment.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Overall, 53 patients were finally enrolled in this study (phase Ia, <i>n</i> = 28; phase Ib, <i>n</i> = 25). In phase Ia part, 1 DLT (grade 4 neutropenia lasting 4 days) was observed in BC001(8 mg/kg) plus paclitaxel cohort. MTD was not reached. All patients experienced TEAEs of any grade. Twenty-four of them suffered ≥ grade 3 TEAEs. leukopenia (<i>n</i> = 33, 62.3%), hemoglobin decreased (<i>n</i> = 32, 60.4%), neutropenia (<i>n</i> = 29, 54.7%) were commonly observed hematological toxicities. The half-life of 140-240 h. And the PK parameters were not largely influenced by combination with paclitaxel. The serum sVEGFR-1, VEGF-A, sVEGFR-2 could not predict the efficacy. Based on the safety, PK and efficacy data, BC001 of 8 mg/kg was determined as RED. Among the GC patients(<i>n</i> = 21) who receiving BC001 plus paclitaxel as 2nd-line treatment in phase 1b part, 6 patients achieved PR and 10 patients experienced SD. The ORR was 28.6% (95% CI 11.3%, 52.2%) and the DCR was 76.2% (95% CI 52.8%, 91.8%), with the median PFS of 5.4 months (95% CI 1.9, 7.0) and OS of 9.4 months (95% CI 5.4, NA). The median DoR was 5.1 months (95% CI 2.6, NA).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>BC001 showed acceptable safety profile and preliminary response in both single-agent and combination with chemotherapy cohorts, especially in GC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674123","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":"Unveiling CKS2: A Key Player in Aggressive B-Cell Lymphoma Progression and a Target for Synergistic Therapy","authors":"Fenling Zhou,&nbsp;Lu Chen,&nbsp;Zhen Liu,&nbsp;Yuli Cao,&nbsp;Cuilan Deng,&nbsp;Gexiu Liu,&nbsp;Chengcheng Liu","doi":"10.1002/cam4.70435","DOIUrl":"10.1002/cam4.70435","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The objective of this study was to investigate the expression levels and biological significance of <i>CKS2</i> in Burkitt cell lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL). Additionally, the potential synergistic anti-tumor effects of <i>CKS2</i> knockdown in combination with etoposide in BL and DLBCL were explored for the first time.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Bioinformatics analysis was utilized to explore the transcriptional levels, prognostic value, and gene function enrichment of <i>CKS2</i> in BL and DLBCL. Specific shRNA sequences were designed to target <i>CKS2</i> for the purpose of constructing a lentiviral expression vector, and therapeutic effects were assessed through analyses of cell proliferation, cell cycle distribution, and cell apoptosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>First, the study examined the increased transcriptional and protein levels of <i>CKS2</i> in BL and DLBCL through analysis of various databases and immunohistochemistry tests. Elevated <i>CKS2</i> expression was found to be correlated with a worse prognosis in BL and DLBCL patients, as evidenced by data from the TCGA and GEO databases. Enrichment analysis indicated that <i>CKS2</i> functions were primarily linked to protein kinase regulatory activity, G1/S phase transition of the cell cycle, and the p53 signaling pathway, among others. Second, stable suppression of <i>CKS2</i> gene expression in Raji and SUDHL6 cells using shRNA resulted in a significant inhibition of cell proliferation. Moreover, <i>CKS2</i>-shRNA induced G0/G1 cell cycle arrest and apoptosis by activating the p53 signaling pathway in Raji and SUDHL6 cells. Third, the combined treatment of <i>CKS2</i>-shRNA and etoposide exhibited a synergistic effect on the proliferation and apoptosis of Raji and SUDHL6 cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our findings suggest that <i>CKS2</i> may play a critical role in the progression of BL and DLBCL and provide evidence for the potential therapeutic application of combining <i>CKS2</i>-shRNA and etoposide agents in the treatment of BL and DLBCL.</p>\u0000 </section>\u0000 </div>","PeriodicalId":139,"journal":{"name":"Cancer Medicine","volume":"13 22","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/cam4.70435","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666522","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}