Article
Biochemistry & Molecular Biology
Ji Hye Kim, Jongwook Kim, Se Seul Im, Ji Hyeon Lee, Sein Hwang, Eun-Ju Chang, Dong-Myung Shin, Jin Kyung Rho, Jaekyoung Son
Summary: The research found that BIX induces apoptotic cell death in EGFR-mutant NSCLC cells and inhibits EGFR signaling, especially in EGFR-TKI resistant cells.
EXPERIMENTAL AND MOLECULAR MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Minzhen Li, Meng Hu, Yanyun Wang, Zhili Xia, Zhilong Li, Juan Li, Danxi Zheng, Xuelian Zheng, Mingrong Xi
Summary: RBPMS is down-regulated in epithelial ovarian cancer and its overexpression inhibits cell proliferation, increases gefitinib sensitivity, and induces cell cycle arrest through the inhibitory effect on the HER2/AKT/mTOR/P70S6K pathway.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
D. Planchard, P. A. Janne, Y. Cheng, J. C. -H. Yang, N. Yanagitani, S-W Kim, S. Sugawara, Y. Yu, Y. Fan, S. L. Geater, K. Laktionov, C. K. Lee, N. Valdiviezo, S. Ahmed, J-M Maurel, I Andrasina, J. Goldman, D. Ghiorghiu, Y. Rukazenkov, A. Todd, K. Kobayashi
Summary: The study indicates that first-line treatment with osimertinib-chemotherapy significantly prolongs progression-free survival compared to osimertinib monotherapy in patients with EGFR-mutated advanced NSCLC.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Article
Oncology
Xiyin Li, Hairui Wang, Xing Yang, Xiaoqi Wang, Lina Zhao, Li Zou, Qin Yang, Zongliu Hou, Jing Tan, Honglei Zhang, Jianyun Nie, Baowei Jiao
Summary: Through research, it was found that GABRP can sustain the stemness of TNBC by modulating EGFR expression, affecting sensitivity to chemotherapy drugs, indicating that GABRP may be a potential therapeutic target.
Article
Chemistry, Medicinal
Hong-Yi Zhao, Hai-Peng Wang, Yu-Ze Mao, Hao Zhang, Minhang Xin, Xiao-Xiao Xi, Hao Lei, Shuai Mao, Dong-Hui Li, San-Qi Zhang
Summary: This study developed proteolysis targeting chimeras (PROTACs) targeting EGFR mutants by optimizing covalent EGFR ligands to overcome drug resistance in non-small-cell lung cancer (NSCLC). The covalent PROTAC CP17 was discovered to be a highly potent degrader against EGFRL858R/T790M and EGFRdel19 with excellent selectivity. Mechanism investigation showed that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be effective for designing PROTACs targeting EGFRL858R/T790M.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Nikolay Bondarev, Karina Ivanenko, Elmira Khabusheva, Timofey Lebedev, Ilya Manukhov, Vladimir Prassolov
Summary: Methionine dependence is a hallmark of malignant cells, and deprivation of methionine can induce cancer cell death. The genetically engineered protein MGL S3 can effectively reduce the number of cancer cells from multiple origins and induce cell death through apoptosis and downregulation of ERK activity. High expression of certain genes in the methionine metabolism pathway is associated with poor prognosis in breast cancer and neuroblastoma patients, and there is a strong correlation between EGFR dependency and DNMT3A/CBS expression in these cancers. Furthermore, MGL S3 enhances the sensitivity of H1299 cells to EGFR inhibitor gefitinib.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Carolien Eggermont, Philippe Giron, Maxim Noeparast, Hugo Vandenplas, Pedro Aza-Blanc, Gustavo J. Gutierrez, Jacques De Greve
Summary: In this study, a high-throughput siRNA kinome screen was performed to identify targets involved in functional drug tolerance against EGFR TKI in NSCLC. STYK1 was identified as a potential target that, when downregulated, enhances the effects of EGFR inhibition. The study also found that STYK1 selectively interacts with mutant EGFR and that its downregulation counteracts the upregulation of FGF1 induced by EGFR TKI. Co-targeting EGFR and STYK1 could lead to a better overall outcome for NSCLC patients.
CELL DEATH & DISEASE
(2022)
Article
Medicine, Research & Experimental
Shigeki Nanjo, Wei Wu, Niki Karachaliou, Collin M. Blakely, Junji Suzuki, Yu-Ting Chou, Siraj M. Ali, D. Lucas Kerr, Victor R. Olivas, Jonathan Shue, Julia Rotow, Manasi K. Mayekar, Franziska Haderk, Nilanjana Chatterjee, Anatoly Urisman, Jia Chi Yeo, Anders J. Skanderup, Aaron C. Tan, Wai Leong Tam, Oscar Arrieta, Kazuyoshi Hosomichi, Akihiro Nishiyama, Seiji Yano, Yuriy Kirichok, Daniel S. W. Tan, Rafael Rosell, Ross A. Okimoto, Trever G. Bivona
Summary: This study investigates the impact of co-occurring genetic alterations on mutant EGFR and identifies the deficiency of RNA-binding factor RBM10 as a factor that decreases the efficacy of EGFR inhibitors in lung cancer treatment. The study reveals that RBM10 modulates tumor cell apoptosis by regulating the alternative splicing of Bcl-x and its deficiency diminishes EGFR inhibitor-mediated apoptosis. The findings suggest that co-occurring genetic alterations and splicing factor deficiency play a role in determining the sensitivity to targeted kinase inhibitor therapy.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Oncology
Hirono Tsutsumi, Eiji Iwama, Ritsu Ibusuki, Atsushi Shimauchi, Keiichi Ota, Yasuto Yoneshima, Hiroyuki Inoue, Kentaro Tanaka, Yoichi Nakanishi, Isamu Okamoto
Summary: In cancer cells without HER2 amplification, HER2 preferentially forms heterodimers with EGFR and is rapidly internalized together with EGFR. The cells with EGFR activating mutations have more HER2-EGFR heterodimers and more efficient transfer of HER2 to lysosomes. Mutant forms of EGFR promote the transfer of HER2-bound T-DM1 to lysosomes through efficient formation of HER2-EGFR heterodimers, making T-DM1 highly cytotoxic. These findings provide a rationale for the use of HER2-targeting ADCs in the treatment of EGFR-mutated lung cancer.
Article
Pharmacology & Pharmacy
Po-Yen Chen, Chin-Chou Wang, Chien-Ning Hsu, Chung-Yu Chen
Summary: This study compared the relative survival rate of gefitinib, erlotinib, and afatinib in EGFR-mutated advanced lung adenocarcinoma patients in Taiwan. Afatinib showed better overall survival and time to treatment failure outcomes compared to gefitinib and erlotinib, especially in patients with initial brain metastases.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Zenghua Sheng, Xu Cao, Ya-nan Deng, Xinyu Zhao, Shufang Liang
Summary: This study reveals that SUMOylation modification of the EGFR-binding protein AnxA6 plays a crucial role in regulating epithelial cancer cell growth and the effectiveness of gefitinib.
CELL COMMUNICATION AND SIGNALING
(2023)
Article
Oncology
Yuki Katayama, Tadaaki Yamada, Shinsaku Tokuda, Naoko Okura, Naoya Nishioka, Kenji Morimoto, Keiko Tanimura, Yoshie Morimoto, Masahiro Iwasaku, Mano Horinaka, Toshiyuki Sakai, Kenji Kita, Seiji Yano, Koichi Takayama
Summary: EGFR-T790M mutation is a major mechanism of acquired resistance to EGFR-TKIs in lung cancer. The biological characteristics of T790M tumors differ based on treatment regimens with each generation of EGFR-TKI. The maintenance of EGFR dependency after acquiring resistance may depend on the type of EGFR-TKI.
Article
Medicine, Research & Experimental
Hui Hua, Jiajia Zeng, Haixin Xing, Yuxin He, Linyu Han, Nasha Zhang, Ming Yang
Summary: This study systematically evaluated the role of genetic variants in A-to-I editing genes on the prognosis of NSCLC patients receiving EGFR-TKIs therapy. The researchers identified several SNPs in the ADAR gene that were significantly associated with patient prognosis and found that silencing ADAR enhanced the sensitivity of NSCLC cells to gefitinib. These findings highlight the importance of A-to-I RNA editing in drug resistance and suggest ADAR as a potential therapeutic target for unresectable NSCLC.
Article
Oncology
Boyeon Kim, Young Soo Park, Jae Sook Sung, Jong Won Lee, Saet Byeol Lee, Yeul Hong Kim
Summary: The study investigated the impact of clathrin-mediated EGFR endocytosis on the efficacy of gefitinib in wild-type EGFR NSCLC cells. The results showed that inhibiting clathrin-mediated endocytosis combined with gefitinib treatment decreased cell survival and induced apoptosis in gefitinib-refractory cell lines. The findings suggest that targeting clathrin-mediated EGFR endocytosis could be a potential option for the treatment of wild-type EGFR NSCLC.
Article
Chemistry, Multidisciplinary
Wei Feng, Xi Chen, Shao-xing Guan, Hong-lian Ruan, Yan Huang, Hui-zhen Zhang, Yun-peng Yang, Wen-feng Fang, Hong-yun Zhao, Wei Zhuang, Shuang Xin, You-hao Chen, Fei Wang, Yue Gao, Min Huang, Xue-ding Wang, Li Zhang
Summary: For NSCLC patients with EGFR sensitive mutations, the standard dose of gefitinib may be too high and could potentially be decreased for better efficacy. The metabolite M2 plays a significant role in efficacy and may be more effective in the treatment of metastatic tumors compared to gefitinib.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Endocrinology & Metabolism
Hiba Alzoubi, Simone Minasi, Francesca Gianno, Manila Antonelli, Francesca Belardinilli, Felice Giangaspero, Marie-Lise Jaffrain-Rea, Francesca Romana Buttarelli
Summary: The study found that a subset of adult PitNETs activate ALT at the onset and maintain it during tumor progression, suggesting it could be used as a predictor of aggressiveness.
ENDOCRINE PATHOLOGY
(2022)
Article
Medicine, General & Internal
Antonio Travaglino, Frediano Inzani, Angela Santoro, Damiano Arciuolo, Alessia Piermattei, Sandra Pasquini, Giulia Scaglione, Nicoletta D'Alessandris, Michele Valente, Antonio Raffone, Francesco Fanfani, Gian Franco Zannoni
Summary: The study found that while neoplasia-associated simple EMRCs may exhibit evident atypia and a worrisome immunophenotype, there is no evidence to support their involvement in endometrial carcinogenesis. Complex metaplastic lesions showed lower Ki67 expression and PTEN loss compared to EMRCs.
Article
Oncology
Crescenzo D'Alterio, Anna Spina, Laura Arenare, Paolo Chiodini, Maria Napolitano, Francesca Galdiero, Luigi Portella, Vittorio Simeon, Simona Signoriello, Francesco Raspagliesi, Domenica Lorusso, Carmela Pisano, Nicoletta Colombo, Gian Franco Zannoni, Nunzia Simona Losito, Rossella De Cecio, Giosue Scognamiglio, Daniela Califano, Daniela Russo, Valentina Tuninetti, Maria Carmela Piccirillo, Piera Gargiulo, Francesco Perrone, Sandro Pignata, Stefania Scala
Summary: Despite advances in research on epithelial ovarian cancer, this study systematically evaluated the CXCR4-CXCL12-CXCR7 axis in tumor and stromal cells, identifying a potential prognostic and therapeutic target in high CXCL12 expression in cancer cells. The study highlights the importance of further investigating the CXCL12 axis to improve treatment efficacy in EOC patients.
Article
Oncology
Francesca Ciccarone, Matteo Bruno, Elisa De Paolis, Alessia Piermattei, Maria De Bonis, Domenica Lorusso, Gian Franco Zannoni, Nicola Normanno, Angelo Minucci, Giovanni Scambia, Gabriella Ferrandina
Summary: Uterine leiomyosarcomas (uLMS) is a rare disease with poor prognosis. Analysis showed that TP53 gene alterations were the most frequent and associated with worse prognosis. Patients with BRCA and HRR-related gene alterations had similar clinical outcomes compared to patients with non-HRR-related gene alterations.
Review
Oncology
Tiziana Feola, Francesca Carbonara, Monica Verrico, Rosa Maria Di Crescenzo, Francesca Gianno, Claudio Colonnese, Antonietta Arcella, Dario de Alcubierre, Silverio Tomao, Vincenzo Esposito, Felice Giangaspero, Giuseppe Minniti, Marie-Lise Jaffrain-Rea
Summary: This study reviewed the effects of ICIs on aggressive/metastatic PitNETs and found that about half of TMZ-resistant PitNETs showed significant benefits from ICIs, with high PDL1 expression associated with remarkable responses but potentially not essential.
Article
Oncology
Maria F. Ianno, Veronica Biassoni, Elisabetta Schiavello, Andrea Carenzo, Luna Boschetti, Lorenza Gandola, Barbara Diletto, Edoardo Marchesi, Claudia Vegetti, Alessandra Molla, Christof M. Kramm, Dannis G. van Vuurden, Patrizia Gasparini, Francesca Gianno, Felice Giangaspero, Piergiorgio Modena, Brigitte Bison, Andrea Anichini, Sabina Vennarini, Emanuele Pignoli, Maura Massimino, Loris De Cecco
Summary: This study demonstrates for the first time that circulating nucleic acids in the blood can serve as powerful and easy-to-assay molecular markers for the disease status of diffuse intrinsic pontine glioma (DIPG), providing valuable prognostic information.
Review
Medicine, General & Internal
Angela Santoro, Antonio Travaglino, Michele Valente, Damiano Arciuolo, Giulia Scaglione, Nicoletta D'Alessandris, Stefania Sfregola, Francesca Addante, Caterina Fulgione, Antonio Raffone, Angelo Minucci, Frediano Inzani, Gian Franco Zannoni
Summary: This study described a case of ovarian PiMHEC and compared it to endometrial PiMHEC. PiMHEC exhibits several consistent clinical, morphological, and immunophenotypical features and requires aggressive management.
Editorial Material
Health Care Sciences & Services
Antonio Raffone, Antonio Travaglino, Diego Raimondo, Paolo Casadio, Renato Seracchioli, Gian Franco Zannoni, Antonio Mollo
Summary: The TCGA-based molecular classifier has been increasingly integrated in the management of endometrial carcinoma. However, there are still unresolved issues regarding the prognostic value of the classifier in each stage and the most suitable adjuvant treatment for each molecular group. Prospective data collected in the future is expected to help resolve these issues.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Oncology
Angela Santoro, Frediano Inzani, Giuseppe Angelico, Damiano Arciuolo, Emma Bragantini, Antonio Travaglino, Michele Valente, Nicoletta D'Alessandris, Giulia Scaglione, Stefania Sfregola, Alessia Piermattei, Federica Cianfrini, Paola Roberti, Gian Franco Zannoni
Summary: The aim of this review is to analyze the most novel and relevant prognostic factors in primary and recurrent cervical cancer. The most relevant factors identified include tumor budding and cell nest size grading system, depth of stromal invasion, lympho-vascular space invasion, perineural invasion, tumor-free distance, and tumor-infiltrating lymphocytes. These factors can be included in the pathology report to aid future studies in understanding cervical cancer prognosis.
Article
Oncology
Nicolo Bizzarri, Damiano Arciuolo, Camilla Certelli, Luigi Pedone Anchora, Valerio Gallotta, Elena Teodorico, Maria Vittoria Carbone, Alessia Piermattei, Francesco Fanfani, Anna Fagotti, Gabriella Ferrandina, Gian Franco Zannoni, Giovanni Scambia, Denis Querleu
Summary: The rate of positive parametrial lymph nodes in apparent early-stage cervical cancer patients undergoing bilateral sentinel lymph node mapping was 3.1%. After ultrastaging of parametrial tissue, no occult micrometastasis was detected. Occult parametrial involvement in apparent early-stage cervical cancer might be overlooked with standard pathologic assessment.
Article
Medicine, General & Internal
Nicoletta D'Alessandris, Angela Santoro, Damiano Arciuolo, Giuseppe Angelico, Michele Valente, Giulia Scaglione, Stefania Sfregola, Angela Carlino, Elena Navarra, Antonino Mule, Gian Franco Zannoni
Summary: This article reports two cases of breast cancer that showed spontaneous tumor regression in the surgical specimen. Spontaneous regression of breast cancer, although rare, is important to understand its mechanism and predict clinical progression.
Review
Biochemistry & Molecular Biology
Angela Santoro, Antonio Travaglino, Frediano Inzani, Giuseppe Angelico, Antonio Raffone, Giuseppe Maria Maruotti, Patrizia Straccia, Damiano Arciuolo, Federica Castri, Nicoletta D'Alessandris, Giulia Scaglione, Michele Valente, Federica Cianfrini, Valeria Masciullo, Gian Franco Zannoni
Summary: Chronic endometritis (CE) is associated with infertility and reproductive failures. The lack of standardized methods to assess plasma cells makes the diagnosis challenging. This study suggests that a threshold of ≥5 plasma cells/10 HPF may be more appropriate for diagnosing CE, as plasma cells at lower levels (<5/10 HPF) may not predict worsened pregnancy outcomes.
Article
Health Care Sciences & Services
Federica Vegni, Nicoletta D'Alessandris, Angela Santoro, Giuseppe Angelico, Giulia Scaglione, Angela Carlino, Damiano Arciuolo, Michele Valente, Stefania Sfregola, Maria Natale, Alejandro Martin Sanchez, Valeria Masciullo, Gian Franco Zannoni, Antonino Mule
Summary: Primary mucinous cystadenocarcinoma (MCA) is a rare subtype of breast carcinoma that shares similarities with mucinous cystadenocarcinoma of the ovary and pancreas. Despite the lack of expression of estrogen receptor, progesterone receptor, and HER-2, as well as high Ki67, primary breast MCAs generally have a favorable prognosis. Only 36 cases have been reported in the literature so far, making the histological diagnosis challenging due to its ambiguous morpho-phenotypic profile. It is important to differentiate it from typical mucin-producing breast carcinomas and metastases from the same histotype in other sites.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Health Care Sciences & Services
Federica Perelli, Giuseppe Vizzielli, Anna Franca Cavaliere, Stefano Restaino, Giovanni Scambia, Gian Franco Zannoni, Damiano Arciuolo, Valerio Gallotta
Summary: This case report describes a 15-year-old female patient with extraskeletal Ewing sarcoma, initially misdiagnosed as an ovarian mass. Through histopathological, immunohistochemical and RT-PCR examinations, the correct diagnosis was made, leading to the administration of optimal treatment including surgery, chemotherapy, and radiotherapy. The patient has achieved a long disease-free interval and has not experienced recurrence to date.
Article
Medicine, General & Internal
Giulia Scaglione, Damiano Arciuolo, Antonio Travaglino, Angela Santoro, Giuseppe Angelico, Saveria Spadola, Frediano Inzani, Nicoletta D'Alessandris, Antonio Raffone, Caterina Fulgione, Belen Padial Urtueta, Stefania Sfregola, Michele Valente, Francesca Addante, Antonio d'Amati, Federica Cianfrini, Alessia Piermattei, Luigi Pedone Anchora, Giovanni Scambia, Gabriella Ferrandina, Gian Franco Zannoni
Summary: In this study, we evaluated the prognostic role of histological response in locally advanced cervical cancer patients. The results showed a significant association between complete pathological response and survival rates. The use of the Mandard scoring system to assess histological response could help in defining post-treatment adjuvant therapy more effectively.