keyword
https://read.qxmd.com/read/37782113/efficacy-and-safety-of-ret-specific-kinase-inhibitors-in-ret-altered-cancers-a-systematic-review
#1
REVIEW
Muhammad Ashar Ali, Syed S Shah, Rimsha Ali, Shammas Farooq Bajwa, Sana Rehman, Aqsa Anwar, Muhammad Yasir Anwar, Memoona Saeed, Nayab Mirza, Wajeeha Aiman
RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60%-89%, 0-11%, and 55%-89%, respectively with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28%-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects...
October 2, 2023: Cancer Investigation
https://read.qxmd.com/read/37779971/design-and-synthesis-of-novel-thieno-3-2-c-quinoline-compounds-with-antiproliferative-activity-on-ret-dependent-medullary-thyroid-cancer-cells
#2
JOURNAL ARTICLE
Gabriele La Monica, Giuseppe Pizzolanti, Concetta Baiamonte, Alessia Bono, Federica Alamia, Francesco Mingoia, Antonino Lauria, Annamaria Martorana
RET kinase gain-of-function mutations represent the main cause of the high aggressiveness and invasiveness of medullary thyroid cancer (MTC). The selective inhibition of the RET kinase is a suitable strategy for the treatment of this endocrine neoplasia. Herein, we performed an innovative ligand-based virtual screening protocol using the DRUDITonline web service, focusing on the RET kinase as a biological target. In this process, thieno[3,2- c ]quinolines 6a-e and 7a-e were proposed as new potential RET inhibitors...
September 26, 2023: ACS Omega
https://read.qxmd.com/read/37779428/retooling-the-ret-inhibitor-pralsetinib-for-esr1-fusion-positive-breast-cancer-and-beyond
#3
EDITORIAL
Jie Wu, Vivek Subbiah
Transcriptionally active fusions of ESR1 (ESR1-TAF) and somatic mutations in the estrogen receptor alpha (ERα) ligand-binding domain (LBD) cause endocrine therapy resistance in breast cancer. In searching for therapeutic target kinase(s) in these breast cancers, Gou and colleagues identified FLT4, RET, JAK1, and IGF1R as the top upregulated kinases induced by ESR1-TAFs and ERα LBD mutants in breast cancer cells. Among them, inhibition of RET by pralsetinib suppressed ESR1-TAF-driven and ERα LBD mutant-driven cell proliferation and patient-derived xenograft growth...
October 2, 2023: Cancer Research
https://read.qxmd.com/read/37775618/macrofollicular-architecture-in-invasive-encapsulated-follicular-variant-of-papillary-thyroid-carcinoma-a-pitfall-in-thyroid-practice
#4
JOURNAL ARTICLE
Sujata Yadav, Devasenathipathy Kandasamy, Nishikant Damle, Rashi Goel, Sunil Chumber, Mehar C Sharma, Monikongkona Boruah, Shipra Agarwal
BACKGROUND: Predominantly macrofollicular architecture in invasive encapsulated follicular variant of papillary thyroid carcinoma (IEFVPTC-MF) is rare and often a cause of misinterpretation during pre-operative work-up and histopathology evaluation. We comprehensively evaluated the radiological, cytological, gross, microscopic, molecular and follow-up characteristics of four such cases, intending to increase its recognition and add our experience to the limited literature available. METHODS: All such histopathologically-proven cases of IEFVPTC-MF were retrieved from the departmental archives...
September 29, 2023: Head and Neck Pathology
https://read.qxmd.com/read/37775370/exploring-the-role-of-immunotherapy-based-treatments-for-advanced-non-small-cell-lung-cancer-with-novel-driver-alterations
#5
JOURNAL ARTICLE
Marta Brambilla, Teresa Beninato, Anna Piemontese, Laura Mazzeo, Chiara Carlotta Pircher, Sara Manglaviti, Paolo Ambrosini, Diego Signorelli, Daniele Lorenzini, Arsela Prelaj, Roberto Ferrara, Claudia Proto, Giuseppe Lo Russo, Elio Gregory Pizzutilo, Monica Ganzinelli, Ilaria Grande, Iolanda Capone, Rosa Maria Di Mauro, Elena Conca, Andra Diana Dumitrascu, Caterina Zanella, Rita Leporati, Simone Rota, Marina Chiara Garassino, Paolo Marchetti, Filippo Maria de Braud, Mario Occhipinti
BACKGROUND: Immunotherapy (IO) single agent or combined with chemotherapy (CT-IO) is the standard treatment for advanced non-small-cell lung cancer (aNSCLC) without driver alterations. IO efficacy in patients with novel driver alterations is not well reported. MATERIALS AND METHODS: Data of aNSCLC patients treated with IO or CT-IO in any line from January 2016 to September 2022 were retrospectively collected. Patients harboring novel driver alterations (m-cohort), including MET exon 14 skipping, BRAF (V600E or atypical), RET rearrangements, HER2 point mutations/exon 20 insertions or uncommon EGFR mutations/EGFR exon 20 insertions, and wild type patients (wt-cohort) were eligible...
August 23, 2023: Clinical Lung Cancer
https://read.qxmd.com/read/37773451/clinical-impact-of-mixed-pulmonary-carcinoma-and-carcinoid-the-driver-from-their-mono-clonal-origin
#6
JOURNAL ARTICLE
Paolo Graziano, Paola Parente, Flavia Centra, Massimo Milione, Giovanni Centonze, Marco Volante, Alberto Cavazza, Diego Urbano, Giuseppe Di Maggio, Teresa Balsamo, Concetta Di Micco, Giulio Rossi, Antonio Rossi, Lucia Anna Muscarella
The combination of neuroendocrine/non neuroendocrine lung tumors (CNNELT) mentioned in the last edition of the World Health Organization (WHO) of Thoracic Tumors refers to small cell carcinoma (SCLC) or large cell neuroendocrine carcinoma (LCNEC) mixed with any other non-small cell lung carcinoma (NSCLC). Typical Carcinoid (TC)/Atypical Carcinoid (AC) combined with NSCLC is not included among this category. However, case reports of TC/AC combined with NSCLC have been described. We previously reported 2 cases of lung adenocarcinoma (LUA) mixed with carcinoid sharing mutations in both components supporting the hypothesis of a clonal origin...
September 29, 2023: Virchows Archiv: An International Journal of Pathology
https://read.qxmd.com/read/37768557/ret-fusion-genes-in-pediatric-and-adult-thyroid-carcinomas-cohort-characteristics-and-prognosis
#7
JOURNAL ARTICLE
Barbora Bulanova Pekova, Vlasta Sykorova, Karolina Mastnikova, Eliska Vaclavikova, Jitka Moravcova, Petr Vlcek, Lucie Lancova, Petr Lastuvka, Rami Katra, Petr Bavor, Daniela Kodetova, Martin Chovanec, Jana Drozenova, Radoslav Matej, Jaromir Astl, Jiri Hlozek, Petr Hrabal, Josef Vcelak, Bela Bendlova
Thyroid cancer is associated with a broad range of different mutations, including RET fusion genes. The importance of characterizing RET fusion-positive tumors has recently increased due to the possibility of targeted treatment. The aim of this study was to identify RET fusion-positive thyroid tumors, correlate them with clinicopathological features, compare them with other mutated carcinomas, and evaluate long-term follow-up of patients. The cohort consisted of 1564 different thyroid tissue samples (including 1164 thyroid carcinoma samples) from pediatric and adult patients...
September 1, 2023: Endocrine-related Cancer
https://read.qxmd.com/read/37761374/indeterminate-thyroid-nodules-from-cytology-to-molecular-testing
#8
REVIEW
Paola Vignali, Elisabetta Macerola, Anello Marcello Poma, Rebecca Sparavelli, Fulvio Basolo
Thyroid cancer is the most common malignancy of the endocrine system. Fine-needle aspiration (FNA) biopsy of thyroid nodules has become the gold standard procedure, in terms of cost and efficacy, for guiding clinicians towards appropriate patients' management. One challenge for cytopathologists is to accurately classify cytological specimens as benign or malignant based on cytomorphological features. In fact, with a frequency ranging from 10% to 30%, nodules are diagnosed as indeterminate. In recent years, the mutational landscape of thyroid tumors has been extensively described, and two molecular profiles have been identified: RAS -like ( NRAS , HRAS, and KRAS mutations; EIF1AX mutations; BRAF K601E mutation; and PPARG and THADA fusions) and BRAF V600E -like (including BRAF V600E mutation and RET and BRAF fusions)...
September 20, 2023: Diagnostics
https://read.qxmd.com/read/37759238/ret-ptc-rearrangement-in-papillary-thyroid-carcinoma-arising-in-malignant-struma-ovarii-with-abdominal-wall-metastasis-and-cervical-thyroid-gland-a-case-report-and-review-of-the-literature
#9
JOURNAL ARTICLE
Maryam Kabootari, Reza Habibi Tirtashi, Azita Zadeh-Vakili, Maryam Zarkesh, Hossein Samadanifard, Shirin Haghighi, Fereidoun Azizi, Atieh Amouzegar
BACKGROUND: Struma ovarii refers to rare mature cystic teratomas containing at least 50% of thyroid tissue, and malignant transformation is known to be even rarer. The synchronous development of malignant struma ovarii and cervical thyroid carcinoma are also scarce and poorly understood due to limited data about molecular features. Here, we present the first report of RET/PTC 1 rearrangement in synchronous metastatic malignant struma ovarii to the abdominal wall and cervical thyroid cancer...
September 27, 2023: Thyroid Research
https://read.qxmd.com/read/37744220/performance-of-multigene-testing-in-cytologically-indeterminate-thyroid-nodules-and-molecular-risk-stratification
#10
JOURNAL ARTICLE
Yuanyuan Zhou, Xinping Wu, Yuzhi Zhang, Zhiqiang Li, Xia Ge, Hao Chen, Yuan Mao, Wenbo Ding
OBJECTIVE: Thyroid cancer is the third most prevalent cancer among females. Genetic testing based on next-generation sequencing may provide an auxiliary diagnosis to reduce cytologically diagnostic uncertainty. However, commercial multigene tests are not widely available and are not well-tested in the Chinese population. METHODS: In this study, we designed a multigene testing panel and evaluated its performance in 529 cytologically indeterminate thyroid nodules (Bethesda III, IV and V)...
2023: PeerJ
https://read.qxmd.com/read/37743366/vepafestinib-is-a-pharmacologically-advanced-ret-selective-inhibitor-with-high-cns-penetration-and-inhibitory-activity-against-ret-solvent-front-mutations
#11
JOURNAL ARTICLE
Isao Miyazaki, Igor Odintsov, Keiji Ishida, Allan J W Lui, Masanori Kato, Tatsuya Suzuki, Tom Zhang, Kentaro Wakayama, Renate I Kurth, Ryan Cheng, Hidenori Fujita, Lukas Delasos, Morana Vojnic, Inna Khodos, Yukari Yamada, Kota Ishizawa, Marissa S Mattar, Kaoru Funabashi, Qing Chang, Shuichi Ohkubo, Wakako Yano, Ryuichiro Terada, Claudio Giuliano, Yue Christine Lu, Annalisa Bonifacio, Siddharth Kunte, Monika A Davare, Emily H Cheng, Elisa de Stanchina, Emanuela Lovati, Yoshikazu Iwasawa, Marc Ladanyi, Romel Somwar
RET receptor tyrosine kinase is activated in various cancers (lung, thyroid, colon and pancreatic, among others) through oncogenic fusions or gain-of-function single-nucleotide variants. Small-molecule RET kinase inhibitors became standard-of-care therapy for advanced malignancies driven by RET. The therapeutic benefit of RET inhibitors is limited, however, by acquired mutations in the drug target as well as brain metastasis, presumably due to inadequate brain penetration. Here, we perform preclinical characterization of vepafestinib (TAS0953/HM06), a next-generation RET inhibitor with a unique binding mode...
September 2023: Nature Cancer
https://read.qxmd.com/read/37741716/improved-survival-outcomes-in-patients-with-met-dysregulated-advanced-nsclc-treated-with-met-inhibitors-results-of-a-multinational-retrospective-chart-review
#12
JOURNAL ARTICLE
Jürgen Wolf, Pierre-Jean Souquet, Koichi Goto, Alexis Cortot, Christina Baik, Rebecca Heist, Tae Min Kim, Ji-Youn Han, Joel W Neal, Aaron S Mansfield, Isabelle Gilloteau, Ngozi Nwana, Maeve Waldron-Lynch, Keith L Davis, Monica Giovannini, Mark M Awad
BACKGROUND: We evaluated the disease and patient characteristics, treatment, and MET testing patterns, predictive biomarkers and survival outcomes in patients with MET-dysregulated metastatic non-small-cell lung cancer (NSCLC) in a real-world setting. PATIENTS AND METHODS: This was a multinational, retrospective, noninterventional chart review study. Data from medical records of patients with advanced/metastatic EGFR wild-type, MET-dysregulated NSCLC (December 2017-September 2018) were abstracted into electronic data collection forms...
August 13, 2023: Clinical Lung Cancer
https://read.qxmd.com/read/37733983/path-less-traveled-targeting-rare-driver-oncogenes-in-non-small-cell-lung-cancer
#13
REVIEW
Sun Min Lim, Jii Bum Lee, Yuko Oya, Jorn Nutzinger, Ross Soo
Over the past decade, tremendous efforts have been made in the development of targeted agents in non-small-cell lung cancer (NSCLC) with nonsquamous histology. Pivotal studies have used next-generation sequencing to select the patient population harboring oncogenic driver alterations that are targetable with targeted therapies. As treatment paradigm rapidly evolves for patients with rare oncogene-driven NSCLC, updated comprehensive overview of diagnostic approach and treatment options is paramount in clinical settings...
September 21, 2023: JCO oncology practice
https://read.qxmd.com/read/37729688/prevalence-of-oncogenic-driver-mutations-in-hispanics-latin-patients-with-lung-cancer-a-systematic-review-and-meta-analysis
#14
JOURNAL ARTICLE
Rafael Parra-Medina, Juan Pablo Castañeda-González, Luisa Montoya, María Paula Gómez-Gómez, Daniel Clavijo Cabezas, Merideidy Plazas Vargas
INTRODUCTION: The frequency of actionable mutations varies between races, and Hispanic/Latino (H/L) people are a population with different proportions of ancestry. Our purpose was to establish prevalence of actionable mutations in the H/L population with NSCLC. METHODS: EMBASE, LILACS, MEDLINE, and Virtual Health Library were searched for studies published up to April 2023 that evaluated the prevalence of ALK, BRAF, EGFR, HER-2, KRAS, MET, NTRK, RET, ROS1 in H/L patients...
September 15, 2023: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://read.qxmd.com/read/37718634/expert-consensus-on-the-diagnosis-and-treatment-of-ret-gene-fusion-non-small-cell-lung-cancer-in-china
#15
JOURNAL ARTICLE
Xingxiang Pu, Chunwei Xu, Qian Wang, Wenxian Wang, Fang Wu, Xiuyu Cai, Zhengbo Song, Jinpu Yu, Wenzhao Zhong, Zhijie Wang, Yongchang Zhang, Jingjing Liu, Shirong Zhang, Anwen Liu, Wen Li, Ping Zhan, Hongbing Liu, Tangfeng Lv, Liyun Miao, Lingfeng Min, Gen Lin, Long Huang, Jingping Yuan, Zhansheng Jiang, Chuangzhou Rao, Dongqing Lv, Zongyang Yu, Xiaoyan Li, Chuanhao Tang, Chengzhi Zhou, Junping Zhang, Hui Guo, Qian Chu, Rui Meng, Xuewen Liu, Jingxun Wu, Jin Zhou, Zhengfei Zhu, Weiwei Pan, Fei Pang, Jintao Huang, Kai Wang, Fan Wu, Tingting Shen, Shirui Zou, Bingwei Xu, Liping Wang, Youcai Zhu, Xinqing Lin, Jing Cai, Ling Xu, Jisheng Li, Xiaodong Jiao, Kainan Li, Huijing Feng, Lin Wang, Yingying Du, Wang Yao, Xuefei Shi, Xiaomin Niu, Dongmei Yuan, Yanwen Yao, Jing Kang, Jiatao Zhang, Chao Zhang, Jianfei Fu, Jianhui Huang, Yinbin Zhang, Pingli Sun, Hong Wang, Mingxiang Ye, Dong Wang, Zhaofeng Wang, Yue Hao, Zhen Wang, Bing Wan, Donglai Lv, Gang Lan, Shengjie Yang, Lin Shi, Yina Wang, Bihui Li, Zhang Zhang, Zhongwu Li, Yuan Li, Zhefeng Liu, Nong Yang, Huijuan Wang, Wenbin Huang, Zhuan Hong, Guansong Wang, Jiandong Wang, Meiyu Fang, Yong Fang, Xixu Zhu, Yi Shen, Yiping Zhang, Shenglin Ma, Yong Song, Yuanzhi Lu, Wenfeng Fang, Ziming Li, Lin Wu
The rearranged during transfection (RET) gene is one of the receptor tyrosine kinases and cell-surface molecules responsible for transmitting signals that regulate cell growth and differentiation. In non-small cell lung cancer (NSCLC), RET fusion is a rare driver gene alteration associated with a poor prognosis. Fortunately, two selective RET inhibitors (sRETi), namely pralsetinib and selpercatinib, have been approved for treating RET fusion NSCLC due to their remarkable efficacy and safety profiles. These inhibitors have shown the ability to overcome resistance to multikinase inhibitors (MKIs)...
September 18, 2023: Thoracic Cancer
https://read.qxmd.com/read/37717273/pheochromocytoma-and-paraganglioma-in-children-and-adolescents
#16
JOURNAL ARTICLE
Teresa Stachowicz-Stencel, Natalia Pasikowska, Anna Synakiewicz
Pheochromocytoma (PPC) and paraganglioma (PGL) are the tumors that rarely occur in the pediatric population (PPGL). Both originate from chromaffin cells, pheochromocytoma is localized in the adrenal gland, whereas paragangliomas are regarded as the tumors present in other localizations, from head to the pelvis. The clinical image is characterized by the presence of the sustained hypertension, headaches, sweating, palpitations. The symptoms are caused by the catecholamine secretion or are related to tumor mass pressure on different organs...
September 17, 2023: Acta Biochimica Polonica
https://read.qxmd.com/read/37716505/a-detailed-histological-and-molecular-assessment-of-the-diffuse-sclerosing-variant-of-papillary-thyroid-carcinoma
#17
JOURNAL ARTICLE
Angela Chou, Min Ru Qiu, Henry Crayton, Bin Wang, Mahsa S Ahadi, John Turchini, Adele Clarkson, Loretta Sioson, Amy Sheen, Nisha Singh, Roderick J Clifton-Bligh, Bruce G Robinson, Matti L Gild, Venessa Tsang, David Leong, Stanley B Sidhu, Mark Sywak, Leigh Delbridge, Ahmad Aniss, Dale Wright, Nicole Graf, Amit Kumar, Vivek Rathi, Paul Benitez-Aguirre, Anthony R Glover, Anthony J Gill
Diffuse sclerosing variant papillary thyroid carcinoma (DS-PTC) is characterized clinically by a predilection for children and young adults, bulky neck nodes and pulmonary metastases. Previous studies have suggested infrequent BRAFV600E mutation but common RET gene rearrangements.Using strict criteria, we studied 43 DS-PTCs (1.9% of unselected PTCs in our unit). 79% harboured pathogenic gene rearrangements involving RET, NTRK3, NTRK1, ALK, or BRAF; with the remainder driven by BRAFV600E mutations. All ten pediatric cases were all gene-rearranged (p=0...
September 14, 2023: Modern Pathology
https://read.qxmd.com/read/37686416/-alk-ros1-ret-and-ntrk1-3-gene-fusions-in-colorectal-and-non-colorectal-microsatellite-unstable-cancers
#18
JOURNAL ARTICLE
Rimma S Mulkidjan, Evgeniya S Saitova, Elena V Preobrazhenskaya, Karimat A Asadulaeva, Mikhail G Bubnov, Ekaterina A Otradnova, Darya M Terina, Sofia S Shulga, Darya E Martynenko, Maria V Semina, Evgeniya V Belogubova, Vladislav I Tiurin, Priscilla S Amankwah, Aleksandr S Martianov, Evgeny N Imyanitov
This study aimed to conduct a comprehensive analysis of actionable gene rearrangements in tumors with microsatellite instability (MSI). The detection of translocations involved tests for 5'/3'-end expression imbalance, variant-specific PCR and RNA-based next generation sequencing (NGS). Gene fusions were detected in 58/471 (12.3%) colorectal carcinomas (CRCs), 4/69 (5.8%) gastric cancers (GCs) and 3/65 (4.6%) endometrial cancers (ECs) ( ALK : 8; RET : 12; NTRK1 : 24; NTRK2 : 2; NTRK3 : 19), while none of these alterations were observed in five cervical carcinomas (CCs), four pancreatic cancers (PanCs), three cholangiocarcinomas (ChCs) and two ovarian cancers (OCs)...
September 2, 2023: International Journal of Molecular Sciences
https://read.qxmd.com/read/37683084/electrochemiluminescent-cds-quantum-dots-biosensor-for-cancer-mutation-detection-at-different-positions-on-linear-dna-analytes
#19
JOURNAL ARTICLE
Fan Yang, JinBo Gong, Ming Li, Xiangyang Jiang, Jiawen Zhang, Meiyan Liao, Hanfei Zhang, Pier-Luc Tremblay, Tian Zhang
PCR-based techniques routinely employed for the detection of mutated linear DNA molecules, including circulating tumor DNA (ctDNA), require large nucleotide sections on both sides of the mutation for primer annealing. This means that DNA fragments with a mutation positioned closer to the extremities are unlikely to be detected. Thus, sensors capable of recognizing linear DNA with characteristic mutations closer to the ends would be advantageous over the state-of-the-art approaches. Here, an electrochemiluminescence-resonance energy transfer (ECL-RET) biosensor comprising capped CdS quantum dots and hairpin DNA probes labeled with Au nanoparticles was developed for the detection of epidermal growth factor receptor (EGFR) ctDNA carrying the critical T790M lung cancer mutation...
September 8, 2023: Analytical Chemistry
https://read.qxmd.com/read/37664946/unraveling-the-mystery-next-generation-sequencing-sheds-light-on-neuroblastoma-pathogenesis-and-targeted-therapies
#20
JOURNAL ARTICLE
Tekincan Aktas, Deniz Kızmazoglu, Safiye Aktas, Aylin Erol, Efe Serinan, Ozde Gokbayrak, Sefayi Merve Ozdemir, Zekiye Altun, Erdener Ozer, Emre Cecen, Dilek Ince, Nur Olgun
BACKGROUND: There is considerable interest in the molecular evaluation of solid tumors in pediatric cases. Although clinical trials are in progress for targeted therapies against neuroblastoma (NB), novel therapeutic strategies are needed for high-risk cases that are resistant to therapy. The aim of the present study was to document the specific gene mutations related to targeted therapy in relapsed or refractory NB patients by using next generation sequencing (NGS). METHODS: The study included 57 NB patients from amongst 1965 neuroblastic cases in Turkey who experienced a recurrence after multi-model therapy...
August 17, 2023: Frontiers in Bioscience (Landmark Edition)
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