Review
Oncology
Serena Ceddia, Giovanni Codacci-Pisanelli
Summary: Brain metastases are common in patients with ALK-translocated non-small cell lung cancer and are typically treated with radiotherapy. However, this can lead to severe late toxic side effects, prompting the use of ALK inhibitors such as crizotinib, alectinib, and brigatinib which have shown excellent activity against brain metastases. Starting treatment with specific inhibitors in asymptomatic patients and using radiotherapy when needed provides the best quality of life for patients.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Haoyue Hu, Songtao Tan, Meng Xie, Peng Guo, Qiang Yu, Juan Xiao, Kangrui Zhao, Qiong Liao, Yi Wang
Summary: In non-small cell lung cancer, concurrent genetic alterations of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are rare, but their clinical and pathological characteristics are not well-defined, and the optimal treatment approach remains controversial. This report presents a case of stage IV lung adenocarcinoma with both EGFR and ALK mutations, along with high PD-L1 expression. The patient initially received treatment with EGFR tyrosine kinase inhibitors (TKIs), but the disease progressed, and regression was achieved following a switch to ALK-TKI therapy and local radiotherapy. Our report also provides a comprehensive summary of the clinical and pathological features, as well as treatment strategies, for NSCLC patients with concurrent EGFR mutation and ALK rearrangement.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Aaron C. Tan, Nick Pavlakis
Summary: The management of advanced lung cancer has been transformed by the identification of targetable oncogenic driver alterations, including ALK gene rearrangements. ALK tyrosine kinase inhibitors have become the first-line treatment options for advanced ALK rearranged NSCLC. However, drug resistance remains a challenge, and the role of anti-angiogenic therapy in ALK rearranged NSCLC needs further exploration.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Marianne Oulhen, Patrycja Pawlikowska, Tala Tayoun, Marianna Garonzi, Genny Buson, Claudio Forcato, Nicolo Manaresi, Agathe Aberlenc, Laura Mezquita, Yann Lecluse, Pernelle Lavaud, Charles Naltet, David Planchard, Benjamin Besse, Francoise Farace
Summary: Gatekeeper mutations are only identified in 50% of cases at resistance to ALK-TKIs. Circulating tumor cells (CTCs) are useful tools in identifying additional resistance mechanisms and can be sequenced at the single-cell level. Comprehensive analysis of CTCs reveals wide copy number alteration (CNA) heterogeneity and high chromosomal instability (CIN) at resistance to ALK-TKIs, providing valuable insights for precision medicine and overcoming resistance to ALK-targeted therapies.
NPJ PRECISION ONCOLOGY
(2021)
Article
Oncology
Ines Mota, Enrico Patrucco, Cristina Mastini, Navin R. Mahadevan, Tran C. Thai, Elisa Bergaggio, Taek-Chin Cheong, Giulia Leonardi, Elif Karaca-Atabay, Marco Campisi, Teresa Poggio, Matteo Menotti, Chiara Ambrogio, Dario L. Longo, Susan Klaeger, Hasmik Keshishian, Zsofia M. Sztupinszki, Zoltan Szallasi, Derin B. Keskin, Jonathan S. Duke-Cohan, Bruce Reinhold, Steven A. Carr, Catherine J. Wu, Kelly D. Moynihan, Darrell J. Irvine, David A. Barbie, Ellis L. Reinherz, Claudia Voena, Mark M. Awad, Rafael B. Blasco, Roberto Chiarle
Summary: Mota et al. demonstrate that immunogenic ALK peptides can enhance the response to immune checkpoint blockade in ALK-rearranged NSCLC mouse models. They also identify immunogenic human ALK peptides for future translational research.
Review
Oncology
Mandy Sakamoto, Tejas Patil
Summary: Targeting the MET pathway is an important approach in the treatment of advanced NSCLC, as it plays a role in both primary oncogenesis and acquired resistance. However, the various mechanisms of MET pathway activation can complicate diagnosis and treatment. Recent developments in MET-directed therapies show promising results. This review summarizes the biology, mechanisms, diagnostic challenges, importance in acquired resistance, and novel treatment strategies of MET in advanced NSCLC.
Review
Oncology
Kamya Sankar, Sunitha Nagrath, Nithya Ramnath
Summary: Non-small cell lung cancer is commonly associated with ALK rearrangements, with approximately 5-6% of cases affected. Although ALK-rearranged tumors respond well to targeted therapies, they are often resistant to immunotherapies. This article explores the mechanisms behind this immune evasion and discusses the potential of novel immunotherapeutic approaches for ALK-rearranged non-small cell lung cancer.
Article
Oncology
Sergi Clave, Jennifer B. Jackson, Marta Salido, Jacob Kames, Kelly M. R. Gerding, Ellen L. Verner, Eric F. Kong, Elizabeth Weingartner, Joan Gibert, Max Hardy-Werbin, Pedro Rocha, Xenia Riera, Erica Torres, James Hernandez, Gustavo Cerqueira, Donna Nichol, John Simmons, Alvaro Taus, Lara Pijuan, Beatriz Bellosillo, Edurne Arriola
Summary: This article introduces the application of next-generation sequencing (NGS) in tumor research and the need for technical optimization for the detection of structural variations.
FRONTIERS IN ONCOLOGY
(2023)
Review
Oncology
Yu Lei, Yan Lei, Xiang Shi, Jingjing Wang
Summary: Non-small cell lung cancer (NSCLC) is a malignant tumor with a high morbidity and mortality rate, and the EML4-ALK fusion gene is one of the most important pathogenic driver genes of NSCLC. With the development of molecular targeted research, the introduction of four generations of targeted drugs for EML4-ALK has significantly benefited patients.
Article
Oncology
Zizong Wang, Yushuai Han, Houquan Tao, Mengxiang Xu, Zhengchuang Liu, Jianhua Zhu, Wei Li, Jie Ma, Zhifang Liu, Weiran Wang, Tonghui Ma
Summary: ALK rearrangement, also known as the 'diamond mutation' in non-small cell lung cancer (NSCLC), plays a crucial role in determining the suitable candidates for ALK inhibitors. In this study, DNA-based next-generation sequencing (NGS) was used to identify ALK rearrangement-positive NSCLC cases and analyze their genomic breakpoints. The findings highlight the necessity of using RNA-based assays to confirm functional RNA fusions in cases with uncommon or frameshift rearrangements.
MOLECULAR ONCOLOGY
(2023)
Article
Oncology
Xing Wang, Natasha Raman, Ghali Lemtiri-Chlieh, Jinhee Chang, Shreya Jagtap, Dipanwita Dutta Chowdhury, Matthew Ballew, Francesca Anna Carrieri, Triet Nguyen, Katriana Nugent, Travis Peck, Michelle S. Levine, Aaron Chan, Christine Lam, Reem Malek, Tung Hoang, Ryan Phillips, ZhuoAn Cheng, Kekoa Taparra, Nick Connis, Christine L. Hann, Andrew Holland, Phuoc T. Tran, Audrey Lafargue, Hailun Wang
Summary: Extra copies of centrosomes are frequently observed in cancer cells and cancer cells have developed strategies to cluster extra-centrosomes. This study investigated the effects of centrosome approved treatment (CCi) and radiotherapy on lung cancer cells, and found that the combination therapy significantly increased the number of NSCLC cells with multipolar spindles, decreased cell viability and colony formation ability in vitro, and delayed tumor growth in vivo. Furthermore, the combination therapy induced the generation of micronuclei and activated cGAS and cGAS-STING pathway in NSCLC cells. These findings suggest that the combination therapy of CCi, radiotherapy, and immunotherapy could be a promising strategy to treat NSCLC.
MOLECULAR CANCER THERAPEUTICS
(2023)
Review
Oncology
Yue Pan, Chao Deng, Zhenhua Qiu, Chenghui Cao, Fang Wu
Summary: This review discusses the resistance mechanisms of ALK TKIs in advanced NSCLC, providing a theoretical basis and research ideas for solving the problem of ALK drug resistance.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Mei Elsayed, Farastuk Bozorgmehr, Daniel Kazdal, Anna-Lena Volckmar, Holger Sueltmann, Jurgen R. Fischer, Mark Kriegsmann, Albrecht Stenzinger, Michael Thomas, Petros Christopoulos
Summary: The study retrospectively analyzed the treatment flow of 145 ALK(+) NSCLC patients receiving TKI therapy, finding that approximately 25-30% of patients forego subsequent systemic therapy due to rapid clinical deterioration. Most patients died under the first failing therapy, indicating the need for closer patient monitoring and broader profiling to support earlier and better directed use of available therapies.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Florian Janke, Arlou Kristina Angeles, Anja Lisa Riediger, Simone Bauer, Martin Reck, Albrecht Stenzinger, Marc A. Schneider, Thomas Muley, Michael Thomas, Petros Christopoulos, Holger Sueltmann
Summary: This study demonstrates the potential of DNA methylation biomarkers in prognosis and therapy monitoring of ALK-positive NSCLC patients. The research highlights the suitability of cfDNA methylation as a non-invasive biomarker for tumor detection and its correlation with other genomic alterations.
CLINICAL EPIGENETICS
(2022)
Review
Oncology
Wen Zhou, Lu-Da Yan, Zhi-Qiong Yu, Na Li, Yong-Hua Yang, Meng Wang, Yuan-Yuan Chen, Meng-Xia Mao, Xiao-Chun Peng, Jun Cai
Summary: ALK inhibitors have shown efficacy in treating ALK-positive NSCLC, but resistance development remains a challenge. The high cost of targeted inhibitors and potential for increased resistance to combination therapy are important issues to address. STK11 mutation may serve as a biomarker for immunotherapy in NSCLC. This review summarizes the role of STK11 in ALK-positive NSCLC and provides an overview of treatment and drug resistance studies.
Meeting Abstract
Hematology
Anthony Hunter, Hannah Newman, Eric Solary, Klaus Geissler, Laura Palomo, Lurdes Zamora, Francesc Sole, Valeria Santini, Timothy A. Graubert, Swapna Thota, Elizabeth A. Griffiths, Lisa Pleyer, Felicitas R. Thol, Rafael Bejar, Luis E. Aguirre, David A. Sallman, Andrew Kuykendall, Rami S. Komrokji, Tracy George, Eric Padron
Meeting Abstract
Hematology
Elisabetta Sauta, Marie Robin, Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Lin-Pierre Zhao, Juan Carlos Caballero Berrocal, Giulia Maggioni, Cristina Astrid Tentori, Massimo Bernardi, Carmen Di Grazia, Luca Vago, Giulia Rivoli, Lorenza Borin, Saverio D'Amico, Marta Ubezio, Alessia Campagna, Antonio Russo, Daniele Mannina, Luca Lanino, Patrizia Chiusolo, Luisa Giaccone, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Olivier Nibourel, Claudia Sala, Marilena Bicchieri, Niccolo Bolli, Alessandro Rambaldi, Francesco Passamonti, Victor Savevski, Armando Santoro, Ulrich Germing, Shahram Kordasti, Valeria Santini, Maria Diez-Campelo, Guillermo Sanz, Francesc Sole, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Castellani Gastone, Matteo G. Della Porta
Meeting Abstract
Hematology
Maria Sirenko, Elsa Bernard, David B. Beck, Maria Creignou, Dylan Domenico, Andrea Farina, Juan E. Arango, Olivier Kosmider, Robert P. Hasserjian, Martin Jadersten, Ulrich Germing, Guillermo Sanz, Arjan A. van de Loosdrecht, Matilde Y. Follo, Felicitas R. Thol, Lurdes Zamora, Ronald Feitosa Pinheiro, Andrea Pellagatti, Harold K. Elias, Detlef Haase, Christina Ganster, Lionel Ades, Magnus Tobiasson, Laura Palomo, Matteo G. Della Porta, Kety Huberman, Pierre Fenaux, Monika Belickova, Michael R. Savona, Virginia M. Klimek, Fabio Pires de Souza Santos, Jacqueline Boultwood, Ioannis Kotsianidis, Valeria Santini, Francesc Sole, Uwe Platzbecker, Michael Heuser, Peter Valent, Carlo Finelli, Maria Teresa Voso, Lee-Yung Shih, Seishi Ogawa, Michaela Fontenay, Joop H. Jansen, Jose Cervera, Benjamin L. Ebert, Rafael Bejar, Peter L. Greenberg, Norbert Gattermann, Luca Malcovati, Mario Cazzola, Eva Hellstrom-Lindberg, Elli Papaemmanuil
Meeting Abstract
Hematology
Aintzane Diaz-Mazkiaran, Jesus De la Fuente, Guillermo Serrano, Paula Garcia-Olloqui, Nerea Berastegui, Marina Ainciburu, Ana Alfonso Pierola, Amaia Vilas-Zornoza, Patxi San Martin-Uriz, Jose Maria Lamo De Espinosa, Mikel San Julian, Pamela Acha, Francesc Sole, Tamara Jimenez, Felix Lopez Cadenas, Maria Diez-Campelo, Antonieta Molero, Maria Julia Montoro, David Valcarcel, Teresa Ezponda, Mikel Hernaez, Felipe Prosper
Meeting Abstract
Hematology
Anna Puiggros, Mar Mallo, Marta Salido, Ana Gomez-Garcia, Adela Cisneros, Rocio Garcia-Serra, Celia Gonzalez-Gil, Gayane Avetisyan, Maria Rodriguez-Rivera, Alvaro Diaz-Gonzalez, Isabel Granada, Esperanza Such, Eulalia Genesca, Rosa Collado, Manuel Ramirez-Orellana, Francesc Sole, Blanca Espinet
Letter
Hematology
Oriol Calvete, Julia Mestre, Arda Durmaz, Carmelo Gurnari, Jaroslaw P. Maciejewski, Francesc Sole
BRITISH JOURNAL OF HAEMATOLOGY
(2023)
Article
Hematology
Giulia Maggioni, Matteo Bersanelli, Erica Travaglino, Ana Alfonso Pierola, Annika Kasprzak, Arnan Sangerman Montserrat, Elisabetta Sauta, Claudia Sala, Tommaso Matteuzzi, Manja Meggendorfer, Matteo Gnocchi, Lin--Pierre Zhao, Cristina Astrid Tentori, Kathrin Nachtkamp, Daniele Dall'Olio, Ettore Mosca, Marta Ubezio, Alessia Campagna, Antonio Russo, Giulia Rivoli, Massimo Bernardi, Lorenza Borin, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Elena Saba, Saverio D'Amico, Luca Lanino, Benedetta Tinterri, Francesca Re, Marilena Bicchieri, Laura Giordano, Giovanni Angelotti, Pierandrea Morandini, Anne Sophie Kubasch, Francesco Passamonti, Alessandro Rambaldi, Victor Savevski, Armando Santoro, Arjan A. van de Loosdrecht, Alice Brogi, Valeria Santini, Shahram Kordasti, Guillermo Sanz, Francesc Sole, Norbert Gattermann, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Ulrich Germing, Maria Diez--Campelo, Matteo G. Della Porta
Summary: This study aimed to describe sex diversity in myelodysplastic syndromes and incorporate sex information into clinical decision-making. The study found differences between men and women in terms of disease genotype, phenotype, and clinical outcomes. Moreover, new prognostic models that included sex information were developed and performed better than the revised International Prognostic Scoring System.
LANCET HAEMATOLOGY
(2023)
Review
Oncology
Pamela Acha, Mar Mallo, Francesc Sole
Summary: Myelodysplastic syndromes with isolated del(5q) are a subtype of MDS defined by cytogenetic alteration. This review summarizes the current knowledge of the molecular background of MDS with isolated del(5q), focusing on the clinical and prognostic relevance of cytogenetic alterations and somatic mutations.
Article
Genetics & Heredity
Alisa Foerster, Claudia Davenport, Nicolas Duployez, Miriam Erlacher, Alina Ferster, Jude Fitzgibbon, Gudrun Goehring, Henrik Hasle, Marjolijn C. Jongmans, Alexandra Kolenova, Geertruijte Kronnie, Tim Lammens, Cristina Mecucci, Wojciech Mlynarski, Charlotte M. Niemeyer, Francesc Sole, Tomasz Szczepanski, Esme Waanders, Andrea Biondi, Marcin Wlodarski, Brigitte Schlegelberger, Tim Ripperger
Summary: Hematologic malignancies are no longer considered sporadic and there is a need for increased awareness of familial cases. Individuals carrying a likely pathogenic germline variant are at an increased risk of developing hematologic malignancies. To ensure high-quality patient care, an European Standard Clinical Practice document has been proposed by an interdisciplinary team of experts to address key issues such as identification of individuals with familial leukemia, genetic analysis, counseling, surveillance, and support. The importance of natural history studies and registries for future evidence-based recommendations is emphasized.
EUROPEAN JOURNAL OF MEDICAL GENETICS
(2023)
Article
Oncology
Elisabetta Sauta, Marie Robin, Matteo Bersanelli, Erica Travaglino, Manja Meggendorfer, Lin-Pierre Zhao, Juan Carlos Caballero Berrocal, Claudia Sala, Giulia Maggioni, Massimo Bernardi, Carmen Di Grazia, Luca Vago, Giulia Rivoli, Lorenza Borin, Saverio D'Amico, Cristina Astrid Tentori, Marta Ubezio, Alessia Campagna, Antonio Russo, Daniele Mannina, Luca Lanino, Patrizia Chiusolo, Luisa Giaccone, Maria Teresa Voso, Marta Riva, Esther Natalie Oliva, Matteo Zampini, Elena Riva, Olivier Nibourel, Marilena Bicchieri, Niccolo' Bolli, Alessandro Rambaldi, Francesco Passamonti, Victor Savevski, Armando Santoro, Ulrich Germing, Shahram Kordasti, Valeria Santini, Maria Diez-Campelo, Guillermo Sanz, Francesc Sole, Wolfgang Kern, Uwe Platzbecker, Lionel Ades, Pierre Fenaux, Torsten Haferlach, Gastone Castellani, Matteo Giovanni Della Porta
Summary: The study validates the effectiveness of the Molecular International Prognostic Scoring System (IPSS-M) in predicting clinical outcomes of patients with myelodysplastic syndromes (MDS). IPSS-M improves the prognostic discrimination of the Revised International Prognostic Scoring System (IPSS-R) and enhances the accuracy of selecting candidates for hematopoietic stem cell transplantation (HSCT).
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Review
Oncology
Oriol Calvete, Julia Mestre, Andres Jerez, Francesc Sole
Summary: The classification of secondary myelodysplastic neoplasms (MDSs) in patients with a previous primary tumor is still controversial due to the lack of an established consensus risk factor-based classification. Current classifications consider separate etiologies based on exposure to cytotoxic therapy and genetic predisposition, despite the evidence of overlapping risk factors. This review aims to summarize the current knowledge of secondary MDS etiologies and suggests the need for future classifications that take into account all risk factors and their interactions.
Article
Oncology
Paula Cabello, Sandra Torres-Ruiz, Anna Adam-Artigues, Jaume Fores-Martos, Maria Teresa Martinez, Cristina Hernando, Sandra Zazo, Juan Madoz-Gurpide, Ana Rovira, Octavio Burgues, Federico Rojo, Joan Albanell, Ana Lluch, Begona Bermejo, Juan Miguel Cejalvo, Pilar Eroles
Summary: The expression of miR-146a-5p is associated with the efficacy and survival of HER2-positive breast cancer patients treated with trastuzumab. Increased expression of miR-146a-5p leads to resistance to trastuzumab and enhances cell migration and angiogenesis, promoting cell cycle progression. Furthermore, exosomes from trastuzumab-resistant cells, which contain high levels of miR-146a-5p expression, can transfer resistance properties to other cells.
Article
Oncology
Sofia Toribio-Castello, Sandra Castano, Angela Villaverde-Ramiro, Esperanza Such, Montserrat Arnan, Francesc Sole, Marina Diaz-Beya, Maria Diez-Campelo, Monica del Rey, Teresa Gonzalez, Jesus Maria Hernandez-Rivas
Summary: This study found that mutations in STAG2, SRSF2 and RUNX1 are independent prognostic factors in isolated +8 MDS, defining the disease's course in terms of overall survival and leukemic transformation. These findings help identify high-risk patients and open new management possibilities for MDS patients with isolated +8.
Meeting Abstract
Hematology
Albert Esquirol, Yolanda Guillen, Elena Bussaglia, Vanesa Criado, Maite Carricondo, Pamela Acha, Manel Esteller, Jorge Sierra, Francesc Sole, Anna Bigas, Josep F. Nomdedeu
Meeting Abstract
Hematology
Pablo Menendez, Clara Bueno, Susana Barrera, Alex Bataller, Valentin Ortiz-Maldonado, Natalina Elliot, Sorcha O'Byrne, Gualing Wang, Montse Rovira, Francisco Gutierrez-Aguera, Juan Trincado, Maria Gonzalez-Gonzalez, Mireia Morgades, Marc Sorigue, Paloma Barcena, Samanta Zanetti, Montse Torrebadell, Nerea Vega, Susana Rives, Mar Mallo, Francesc Sole, Adam Mead, Irene Roberts, Supat Thongjuea, Bethan Psaila, Manel Juan, Julio Delgado, Alvaro Urbano-Ispizua, Jose Ribera, Alberto Orfao, Anindita Roy
EXPERIMENTAL HEMATOLOGY
(2022)