keyword
https://read.qxmd.com/read/38529509/overcoming-brain-derived-therapeutic-resistance-in-her2-breast-cancer-brain-metastasis
#1
Danyyl Ippolitov, Yi-Han Lin, Jeremy Spence, Aleksandra Glogowska, Thatchawan Thanasupawat, Jason Beiko, Marc R Del Bigio, Xin Xu, Amy Wang, Raul Calvo, Abhijeet Kapoor, Juan J Marugan, Mark J Henderson, Thomas Klonisch, Sabine Hombach-Klonisch
Brain metastasis of HER2+ breast cancer occurs in about 50% of all women with metastatic HER2+ breast cancer and confers poor prognosis for patients. Despite effective HER2-targeted treatments of peripheral HER2+ breast cancer with Trastuzumab +/-HER2 inhibitors, limited brain permeability renders these treatments inefficient for HER2+ breast cancer brain metastasis (BCBM). The scarcity of suitable patient-derived in-vivo models for HER2+ BCBM has compromised the study of molecular mechanisms that promote growth and therapeutic resistance in brain metastasis...
February 22, 2024: bioRxiv
https://read.qxmd.com/read/38507923/nuf2-regulated-the-progression-of-hepatocellular-carcinoma-through-modulating-the-pi3k-akt-pathway-via-stabilizing-erbb3
#2
JOURNAL ARTICLE
Yiwei Liu, Yuming Wang, Jifei Wang, Wangjie Jiang, Yananlan Chen, Jijun Shan, Xiao Li, Xiaofeng Wu
Hepatocellular carcinoma (HCC) is among the most prevalent and lethal cancers worldwide. The NDC80 kinetochore complex component NUF2 has been previously identified as up-regulating in HCC and associated with patient prognosis. However, the pathophysiological effects and molecular mechanisms of NUF2 in tumorigenesis remain unclear. In this study, we confirmed a significant increase in NUF2 expression in HCC tissues and established a correlation between high NUF2 expression and adverse outcomes in HCC patients...
March 19, 2024: Translational Oncology
https://read.qxmd.com/read/38502852/genomic-and-immune-microenvironment-features-influencing-chemoimmunotherapy-response-in-gastric-cancer-with-peritoneal-metastasis-a-retrospective-cohort-study
#3
JOURNAL ARTICLE
Pengfei Yu, Guangyu Ding, Xingmao Huang, Chenxuan Wang, Jingquan Fang, Ling Huang, Zeyao Ye, Qi Xu, Xiaoying Wu, Junrong Yan, Qiuxiang Ou, Yian Du, Xiangdong Cheng
BACKGROUND: Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. MATERIALS AND METHODS: A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting...
March 19, 2024: International Journal of Surgery
https://read.qxmd.com/read/38482714/clonal-analysis-of-metachronous-double-biliary-tract-cancers
#4
JOURNAL ARTICLE
Yuko Omori, Shuichi Aoki, Yusuke Ono, Takashi Kokumai, Shingo Yoshimachi, Hideaki Sato, Akiko Kusaka, Masahiro Iseki, Daisuke Douchi, Takayuki Miura, Shimpei Maeda, Masaharu Ishida, Masamichi Mizuma, Kei Nakagawa, Yusuke Mizukami, Toru Furukawa, Michiaki Unno
The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled...
March 14, 2024: Journal of Pathology
https://read.qxmd.com/read/38428737/molecular-and-clinical-portrait-of-her2-low-invasive-lobular-carcinomas
#5
JOURNAL ARTICLE
Lounes Djerroudi, Ahmad El Sabeh-Ayoun, Camille Benoist, Gaelle Pierron, Julien Masliah-Planchon, Laetitia Fuhrmann, Yann Kieffer, Matthieu Carton, Toulsie Ramtohul, Celine Callens, Victor Renault, François-Clément Bidard, Fatima Mechta-Grigoriou, Anne Vincent-Salomon
Invasive lobular carcinomas (ILCs) have a low frequency of ERBB2 amplification, therefore restricting the use of conventional anti-HER2 therapies for this histological special type. Conversely, ILCs with low HER2 overexpression may represent a broader target for the use of emerging anti-body drug conjugate therapies targeting HER2, since these treatments have proven effective in HER2-low breast cancers. Very scarce data about HER2-low ILCs have been so far published, although these tumors could have different prevalence and histo-molecular specificities compared to invasive breast carcinoma of no special type (IBC-NST)...
February 28, 2024: Modern Pathology
https://read.qxmd.com/read/38414979/expert-consensus-on-the-diagnosis-and-treatment-of-nrg1-2-gene-fusion-solid-tumors
#6
REVIEW
Chunwei Xu, Qian Wang, Dong Wang, Wenxian Wang, Wenfeng Fang, Ziming Li, Aijun Liu, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Xiuyu Cai, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Yu Chen, Jingping Yuan, Feng Wang, Zhansheng Jiang, Gen Lin, Long Huang, Xingxiang Pu, Rongbo Lin, Weifeng Liu, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Xiaoyan Li, Chuanhao Tang, Chengzhi Zhou, Junping Zhang, Junli Xue, Hui Guo, Qian Chu, Rui Meng, Jingxun Wu, Rui Zhang, Jin Zhou, Zhengfei Zhu, Yongheng Li, Hong Qiu, Fan Xia, Yuanyuan Lu, Xiaofeng Chen, Rui Ge, Enyong Dai, Yu Han, Weiwei Pan, Fei Pang, Qingqing He, Jintao Huang, Kai Wang, Fan Wu, Bingwei Xu, Liping Wang, Youcai Zhu, Li Lin, Yanru Xie, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Jia Wei, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jianhui Huang, Yue Feng, Yinbin Zhang, Pingli Sun, Hong Wang, Mingxiang Ye, Zhaofeng Wang, Yue Hao, Zhen Wang, Bin Wan, Donglai Lv, Shengjie Yang, Jin Kang, Jiatao Zhang, Chao Zhang, Juanjuan Ou, Lin Shi, Yina Wang, Bihui Li, Zhang Zhang, Zhongwu Li, Zhefeng Liu, Nong Yang, Lin Wu, Huijuan Wang, Gu Jin, Guansong Wang, Jiandong Wang, Meiyu Fang, Yong Fang, Yuan Li, Xiaojia Wang, Yiping Zhang, Xixu Zhu, Yi Shen, Shenglin Ma, Biyun Wang, Lu Si, Yong Song, Yuanzhi Lu, Jing Chen, Zhengbo Song
The fusion genes NRG1 and NRG2 , members of the epidermal growth factor (EGF) receptor family, have emerged as key drivers in cancer. Upon fusion, NRG1 retains its EGF-like active domain, binds to the ERBB ligand family, and triggers intracellular signaling cascades, promoting uncontrolled cell proliferation. The incidence of NRG1 gene fusion varies across cancer types, with lung cancer being the most prevalent at 0.19 to 0.27%. CD74 and SLC3A2 are the most frequently observed fusion partners. RNA-based next-generation sequencing is the primary method for detecting NRG1 and NRG2 gene fusions, whereas pERBB3 immunohistochemistry can serve as a rapid prescreening tool for identifying NRG1 -positive patients...
January 2024: Global medical genetics
https://read.qxmd.com/read/38369520/neuregulin-1-and-als19-erbb4-at-the-crossroads-of-amyotrophic-lateral-sclerosis-and-cancer
#7
REVIEW
Jacob J Adashek, Chinmayi Pandya, Nicholas J Maragakis, Pradip De, Philip R Cohen, Shumei Kato, Razelle Kurzrock
BACKGROUND: Neuregulin-1 (NRG1) is implicated in both cancer and neurologic diseases such as amyotrophic lateral sclerosis (ALS); however, to date, there has been little cross-field discussion between neurology and oncology in regard to these genes and their functions. MAIN BODY: Approximately 0.15-0.5% of cancers harbor NRG1 fusions that upregulate NRG1 activity and hence that of the cognate ERBB3/ERBB4 (HER3/HER4) receptors; abrogating this activity with small molecule inhibitors/antibodies shows preliminary tissue-agnostic anti-cancer activity...
February 19, 2024: BMC Medicine
https://read.qxmd.com/read/38369013/translational-insights-and-overall-survival-in-the-u31402-a-u102-study-of-patritumab-deruxtecan-her3-dxd-in-egfr-mutated-nsclc
#8
JOURNAL ARTICLE
H A Yu, C Baik, D-W Kim, M L Johnson, H Hayashi, M Nishio, J C-H Yang, W-C Su, K A Gold, M Koczywas, E F Smit, C E Steuer, E Felip, H Murakami, S-W Kim, X Su, S Sato, P-D Fan, M Fujimura, Y Tanaka, P Patel, D Sternberg, D Sellami, P A Jänne
BACKGROUND: HER3 is broadly expressed in NSCLC and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase 1 study of HER3-DXd in patients with advanced NSCLC. Patients with EGFR-mutated NSCLC that progressed after EGFR TKI and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%...
February 16, 2024: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://read.qxmd.com/read/38339127/targeting-pi3k-akt-mtor-and-mapk-signaling-pathways-in-gastric-cancer
#9
REVIEW
Diana-Theodora Morgos, Constantin Stefani, Daniela Miricescu, Maria Greabu, Silviu Stanciu, Silvia Nica, Iulia-Ioana Stanescu-Spinu, Daniela Gabriela Balan, Andra-Elena Balcangiu-Stroescu, Elena-Claudia Coculescu, Dragos-Eugen Georgescu, Remus Iulian Nica
Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year. Helicobacter pylori represents the main risk factor, being responsible for 78% of the cases. Increased amounts of salt, pickled food, red meat, alcohol, smoked food, and refined sugars negatively affect the stomach wall, contributing to GC development. Several gene mutations, including PIK3CA , TP53 , ARID1A , CDH1 , Ras , Raf , and ERBB3 are encountered in GC pathogenesis, leading to phosphatidylinositol 3-kinase (PI3K) protein kinase B (AKT)/mammalian target of rapamycin (mTOR)-PI3K/AKT/mTOR-and mitogen-activated protein kinase (MAPK) signaling pathway activation and promoting tumoral activity...
February 3, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38306015/erbb3-overexpression-is-enriched-in-diverse-patient-populations-with-castration-sensitive-prostate-cancer-and-is-associated-with-a-unique-ar-activity-signature
#10
JOURNAL ARTICLE
Jordan E Vellky, Brenna J Kirkpatrick, Lisa C Gutgesell, Mathias Morales, Ryan M Brown, Yaqi Wu, Mark Maienschein-Cline, Lucia D Notardonato, Michael S Weinfeld, Ryan H Nguyen, Eileen Brister, Maria Sverdlov, Li Liu, Ziqiao Xu, Steven Kregel, Larisa Nonn, Donald J Vander Griend, Natalie M Reizine
PURPOSE: Despite successful clinical management of castration-sensitive prostate cancer (CSPC), the 5-year survival rate for men with castration-resistant prostate cancer (CRPC) is only 32%. Combination treatment strategies to prevent disease recurrence are increasing, albeit in biomarker-unselected patients. Identifying a biomarker in CSPC to stratify patients who will progress on standard-of-care therapy could guide therapeutic strategies. METHODS: Targeted deep sequencing was performed for the UI cohort (n=30), and immunostaining was performed on a patient tissue microarray (n=149)...
February 2, 2024: Clinical Cancer Research
https://read.qxmd.com/read/38276060/deciphering-the-role-of-erbb3-isoforms-in-renal-cell-carcinoma-a-comprehensive-genomic-and-transcriptomic-analysis
#11
JOURNAL ARTICLE
Mingyu Kim, Hyung Ho Lee, So Dam Won, YeonSue Jang, Baek Gil Kim, Nam Hoon Cho, Young Deuk Choi, Jin Soo Chung, Hyun Ho Han
ERBB3, a key member of the receptor tyrosine kinase family, is implicated in the progression and development of various human cancers, affecting cellular proliferation and survival. This study investigated the expression of ERBB3 isoforms in renal clear cell carcinoma (RCC), utilizing data from 538 patients from The Cancer Genome Atlas (TCGA) Firehose Legacy dataset. Employing the SUPPA2 tool, the activity of 10 ERBB3 isoforms was examined, revealing distinct expression patterns in RCC. Isoforms uc001sjg.3 and uc001sjh...
January 20, 2024: Medicina
https://read.qxmd.com/read/38223603/expression-of-mir-152-in-cervical-cancer-and-its-influence-on-cisplatin-resistance
#12
JOURNAL ARTICLE
Jun Wu, Xiaoping Chi, Qian Yang, Jinxiao Li
BACKGROUND: Cervical cancer has a high mortality rate. AIM: We aimed to study the expression of micro ribonucleic acid 152 (miR-152) in cervical cancer and its influence on cisplatin (DDP) resistance. METHODOLOGY: Cervical cancer Hela cells were divided into control, DDP, DDP + mimic nc and DDP + miR-152 mimic groups. RESULTS: DDP, DDP + mimic nc and DDP + miR-152 mimic groups had lower cell survival rate, smaller number of single clones and cells penetrating the membrane, and higher apoptosis rate and miR-152 expression than those of the control group (P<0...
June 2023: African Health Sciences
https://read.qxmd.com/read/38216592/conformational-diversity-and-protein-protein-interfaces-in-drug-repurposing-in-ras-signaling-pathway
#13
JOURNAL ARTICLE
Ahenk Zeynep Sayin, Zeynep Abali, Simge Senyuz, Fatma Cankara, Attila Gursoy, Ozlem Keskin
We focus on drug repurposing in the Ras signaling pathway, considering structural similarities of protein-protein interfaces. The interfaces formed by physically interacting proteins are found from PDB if available and via PRISM (PRotein Interaction by Structural Matching) otherwise. The structural coverage of these interactions has been increased from 21 to 92% using PRISM. Multiple conformations of each protein are used to include protein dynamics and diversity. Next, we find FDA-approved drugs bound to structurally similar protein-protein interfaces...
January 12, 2024: Scientific Reports
https://read.qxmd.com/read/38175774/adipocyte-precursor-derived-nrg1-promotes-resistance-to-fgfr-inhibition-in-urothelial-carcinoma
#14
JOURNAL ARTICLE
Sana Hosni, Viola Kilian, Niklas Klümper, Daniela Gabbia, Katharina Sieckmann, Dillon Corvino, Anja Winkler, Miriam Saponaro, Karin Woersdoerfer, Doris Schmidt, Oliver Hahn, Ilaria Zanotto, Marina Bertlich, Marieta Toma, Tobias Bald, Markus Eckstein, Michael Hölzel, Matthias Geyer, Manuel Ritter, Dagmar Wachten, Sara De Martin, Abdullah Alajati
Aberrations of the fibroblast growth factor receptor (FGFR) family members are frequently observed in metastatic urothelial cancer (mUC), and blocking the FGF/FGFR signaling axis is used as a targeted therapeutic strategy for treating patients. Erdafitinib is a pan-FGFR inhibitor that has recently been approved by the Food and Drug Administration for mUC with FGFR2/3 alterations. Although mUC patients show initial response to erdafitinib, acquired resistance rapidly develops. Here, we found that adipocyte precursors promoted resistance to erdafitinib in FGFR-dependent bladder and lung cancer in a paracrine manner...
January 4, 2024: Cancer Research
https://read.qxmd.com/read/38144565/exploration-and-validation-of-key-genes-associated-with-early-lymph-node-metastasis-in-thyroid-carcinoma-using-weighted-gene-co-expression-network-analysis-and-machine-learning
#15
JOURNAL ARTICLE
Yanyan Liu, Zhenglang Yin, Yao Wang, Haohao Chen
BACKGROUND: Thyroid carcinoma (THCA), the most common endocrine neoplasm, typically exhibits an indolent behavior. However, in some instances, lymph node metastasis (LNM) may occur in the early stages, with the underlying mechanisms not yet fully understood. MATERIALS AND METHODS: LNM potential was defined as the tumor's capability to metastasize to lymph nodes at an early stage, even when the tumor volume is small. We performed differential expression analysis using the 'Limma' R package and conducted enrichment analyses using the Metascape tool...
2023: Frontiers in Endocrinology
https://read.qxmd.com/read/38131395/site-specific-genetic-differences-in-colorectal-cancer-via-next-generation-sequencing-using-a-multigene-panel
#16
JOURNAL ARTICLE
Ahmet Rencuzogullari, Atil Bisgin, Kivilcim Eren Erdogan, Serdar Gumus, Orcun Yalav, Ibrahim Boga, Ozge Sonmezler, Ismail Cem Eray
AIM: Next-generation sequencing (NGS) has been proposed as a comprehensive and efficient genomic profiling tool to guide personalized therapy for colorectal cancer. This study aimed to review the site-specific difference and the potential benefits of actionable mutation panel for colorectal cancer in relation to the clinicopathological features. MATERIAL AND METHODS: One hundred and six patients who underwent colorectal surgery with curative or palliative intent for histopathologically confirmed carcinoma between June 2016 and June 2018 were identified from a prospectively maintained database...
2023: Annali Italiani di Chirurgia
https://read.qxmd.com/read/38092140/cd44s-and-cd44v8-10-isoforms-confer-acquired-resistance-to-osimertinib-by-activating-the-erbb3-stat3-signaling-pathway
#17
JOURNAL ARTICLE
Yi-Nan Liu, Meng-Feng Tsai, Shang-Gin Wu, Tzu-Hua Chang, Jin-Yuan Shih
AIMS: Although epidermal growth factor receptor (EGFR)-mutant lung cancers respond well to osimertinib, acquired resistance to osimertinib eventually develops through EGFR-dependent and EGFR-independent resistance mechanisms. CD44 splicing variants are widely expressed in lung cancer tissues. However, it remains unclear whether specific splicing variants are involved in acquired resistance to osimertinib. MAIN METHODS: The real-time PCR was performed to measure the expression levels of total CD44 and specific CD44 splicing variants (CD44s or CD44v)...
December 11, 2023: Life Sciences
https://read.qxmd.com/read/38001709/expression-of-soluble-form-of-aurora-a-as-a-predictive-factor-for-neoadjuvant-therapy-in-breast-cancer-patients-a-single-center-pilot-study
#18
JOURNAL ARTICLE
Pawel Winter, Malgorzata Fuksiewicz, Agnieszka Jagiello-Gruszfeld, Zbigniew Nowecki, Beata Kotowicz
PURPOSE: To search for new predictive breast cancer biomarkers. We analyzed the serum concentrations of biomarkers involved in carcinogenesis, which can also be targeted by therapy. METHODS: In a single-center prospective study, the serum levels of Aurora A, thymidine kinase 1, and human epidermal growth factor receptor type 3 (HER3) were determined in 119 women with BC before neoadjuvant treatment using ELISA kits. RESULTS: The following clinical data were analyzed: age; TNM; the expression of ER, PGR, HER2, and Ki67; histological grade (G); and the response to neoadjuvant treatment (NAT) in the residual tumor burden classification (RCB)...
November 16, 2023: Cancers
https://read.qxmd.com/read/37878223/architecture-and-topologies-of-gene-regulatory-networks-associated-with-breast-cancer-adjacent-normal-and-normal-tissues
#19
JOURNAL ARTICLE
Swapnil Kumar, Vaibhav Vindal
Most cancer studies employ adjacent normal tissues to tumors (ANTs) as controls, which are not completely normal and represent a pre-cancerous state. However, the regulatory landscape of ANTs compared to tumor and non-tumor-bearing normal tissues is largely unexplored. Among cancers, breast cancer is the most commonly diagnosed cancer and a leading cause of death in women worldwide, with a lack of sufficient treatment regimens for various reasons. Hence, we aimed to gain deeper insights into normal, pre-cancerous, and cancerous regulatory systems of breast tissues towards identifying ANT and subtype-specific candidate genes...
October 25, 2023: Functional & Integrative Genomics
https://read.qxmd.com/read/37775182/stromal-derived-nrg1-enables-oncogenic-kras-bypass-in-pancreas-cancer
#20
JOURNAL ARTICLE
Jincheng Han, Jiaqian Xu, Yonghong Liu, Shaoheng Liang, Kyle A LaBella, Deepavali Chakravarti, Denise J Spring, Yan Xia, Ronald A DePinho
Activating KRAS mutations (KRAS*) in pancreatic ductal adenocarcinoma (PDAC) drive anabolic metabolism and support tumor maintenance. KRAS* inhibitors show initial antitumor activity followed by recurrence due to cancer cell-intrinsic and immune-mediated paracrine mechanisms. Here, we explored the potential role of cancer-associated fibroblasts (CAFs) in enabling KRAS* bypass and identified CAF-derived NRG1 activation of cancer cell ERBB2 and ERBB3 receptor tyrosine kinases as a mechanism by which KRAS*-independent growth is supported...
September 29, 2023: Genes & Development
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