Review
Biochemistry & Molecular Biology
Ilio Vitale, Efrat Shema, Sherene Loi, Lorenzo Galluzzi
Summary: Tumors evolve under various pressures and exhibit considerable heterogeneity in genetic, phenotypic, and behavioral aspects. This intratumoral heterogeneity influences disease progression and treatment sensitivity, necessitating consideration of multiple levels of heterogeneity in future therapeutic approaches.
Review
Biochemistry & Molecular Biology
Taylor M. Parker, Kartik Gupta, Antonio M. Palma, Michail Yekelchyk, Paul B. Fisher, Steven R. Grossman, Kyoung Jae Won, Esha Madan, Eduardo Moreno, Rajan Gogna
Summary: Tumors are complex environments where cancer cells are constantly under selection pressures, competing with each other and the microenvironment. Less-fit cells are typically eliminated by fitter cells through apoptosis, and these competitive interactions play a role in tumor growth, metastasis, and therapy outcomes. Sophisticated pathways such as Flower, Hippo, Myc, and p53 signaling are involved in cell competition mechanisms, contributing to the evolution, growth, and treatment of cancer.
Review
Oncology
Xiaodi Lv, Zixian Mao, Xianjun Sun, Baojun Liu
Summary: The diagnosis and treatment of lung cancer is challenging due to intratumoral heterogeneity. While previous research has revealed various mechanisms and characteristics of intratumoral heterogeneity in lung cancer, a comprehensive discussion on the topic is still lacking. This review provides an overview of how intratumoral heterogeneity develops over space and time in lung cancer. It discusses the intricate details and impacts of each aspect of intratumoral heterogeneity and explores their relationships. Based on these findings, a more accurate multidisciplinary therapeutic strategy and potential approach for lung cancer therapy are proposed.
Review
Cell Biology
Yoshinobu Hirose, Kohei Taniguchi
Summary: The metabolic phenotype of tumors differs greatly from surrounding normal tissue, and the importance of this heterogeneity is increasingly recognized. This review classifies metabolic phenomena in colorectal cancer (CRC) into extrinsic and intrinsic factors, identifying their impact on tumor function. The study redefines characteristics of specific metabolism-related factors in CRC and emphasizes the significance of tumor budding as a form of metabolic heterogeneity.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Oncology
Nan Qin, Eunice Paisana, Maike Langini, Daniel Picard, Bastian Malzkorn, Carlos Custodia, Rita Cascao, Frauke-Dorothee Meyer, Lena Bluemel, Sarah Goebbels, Kuebra Taban, Jasmin Bartl, Nicole Bechmann, Catleen Conrad, Jan Gravemeyer, Juergen C. Becker, Anja Stefanski, Stephanie Puget, Joao T. Barata, Kai Stuehler, Ute Fischer, Joerg Felsberg, Olivier Ayrault, Guido Reifenberger, Arndt Borkhardt, Graeme Eisenhofer, Claudia C. Faria, Marc Remke
Summary: The study highlights the importance of interclonal cross-talk between MYC-driven and non-MYC-driven cells in medulloblastoma, showing how their interactions influence metastasis, angiogenesis, and tumor progression. Targeting the secretome can effectively suppress this communication between subclones.
Review
Oncology
Yanjun Hou, Hiroaki Nitta, Zaibo Li
Summary: HER2 intratumoral heterogeneity (ITH) is a common phenomenon in breast cancer, characterized by the coexistence of tumor cell subpopulations with different HER2 gene or protein expression. It has been associated with poor prognosis in patients receiving anti-HER2 targeted therapies and proposed as a potential mechanism for anti-HER2 resistance. HER2 ITH can be categorized into non-genetic and genetic ITH based on different HER2 genetic amplification, with genetic ITH exhibiting clustered, mosaic, and scattered distribution patterns. Digital image analysis has emerged as a promising method to accurately and objectively assess HER2 ITH.
Article
Chemistry, Analytical
Kideog Bae, Le Xin, Wei Zheng, Carol Tang, Beng-Ti Ang, Zhiwei Huang
Summary: Recent genomic studies have paved the way for effective clinical treatments of glioblastoma (GBM) subtypes, but intratumoral heterogeneity complicates subtype identification. The use of hyperspectral stimulated Raman scattering (SRS) microscopy allows for rapid, label-free molecular assessment of GBM intratumoral heterogeneity. By developing a unique SRS imaging diagnostic platform, it is possible to accurately determine tumor heterogeneity in GBM tissues, thus potentially improving targeted therapy for GBM in the future.
ANALYTICAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Yuanyuan Zhao, Bing Zhang, Yiming Ma, Fuqiang Zhao, Jianan Chen, Bingzhi Wang, Hua Jin, Fulai Zhou, Jiawei Guan, Qian Zhao, Hongying Wang, Qian Liu, Fangqing Zhao, Xia Wang
Summary: This study establishes an innovative model for studying intratumor functional heterogeneity in personalized oncology. The model efficiently replicates the genomic landscape of patient-derived cancer cells and tumors, while retaining the histological architecture. Moreover, it is found that tumorigenic cancer cells do not necessarily possess stem cell characteristics.
Article
Chemistry, Multidisciplinary
Kewei Wang, Maolin Jiang, Jielian Zhou, Yansong Dong, Ye Liu, Qingyu Zong, Puja Sandbhor, N. D. Pradeep Singh, Youyong Yuan
Summary: In this study, a tumor-acidity and bioorthogonal chemistry mediated in situ size transformable nanocarrier was developed to spatially deliver two combinational chemotherapeutic drugs to combat hypoxia-induced intratumoral heterogeneity. The results demonstrated that this site-specific combination chemotherapy is better than the traditional combination chemotherapy.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Chemistry, Multidisciplinary
Soon-Chan Kim, Ji Won Park, Ha-Young Seo, Minjung Kim, Jae-Hyeon Park, Ga-Hye Kim, Ja Oh Lee, Young-Kyoung Shin, Jeong Mo Bae, Bon-Kyoung Koo, Seung-Yong Jeong, Ja-Lok Ku
Summary: The study reveals the widespread subregional heterogeneity within single tumors, leading to varied drug responses, emphasizing the importance of understanding the molecular heterogeneity of each tumor and targeting common somatic driver mutations positioned in all tumor subregional clones.
Review
Immunology
Fei-Qi Xu, Meng-Meng Dong, Zhi-Fei Wang, Li-Dong Cao
Summary: Liver cancer, particularly hepatocellular carcinoma (HCC), is a common and difficult to diagnose malignant tumor with limited treatment options and poor prognosis. Aggressive cancer cells in HCC undergo extensive metabolic rewiring, leading to adaptation to the tumor microenvironment. Intratumoral heterogeneity (ITH), characterized by distinct genetic and phenotypic features in the same tumor region, is unique to malignant tumors and contributes to differences in tumor growth, chemotherapy resistance, and metabolic reprogramming. Understanding the associations between glucose metabolism reprogramming, tumoral heterogeneity, and HCC oncogenesis is crucial for better insights into HCC mechanisms.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Multidisciplinary Sciences
Priyanka Gopal, Aaron Petty, Kevin Rogacki, Titas Bera, Rohan Bareja, Craig D. Peacock, Mohamed E. Abazeed
Summary: This study identifies distinct transcriptional states in individual small cell lung carcinoma (SCLC) tumors and reveals their discrete functional attributes. The research also highlights the presence of stable cellular states governed by bidirectional cell state transitions in SCLC tumors. By altering individual state transition rates, the composition of tumor states can be reconfigured.
Article
Oncology
Amber N. N. Hurson, Alina M. M. Hamilton, Linnea T. T. Olsson, Erin L. L. Kirk, Mark E. E. Sherman, Benjamin C. C. Calhoun, Joseph Geradts, Melissa A. A. Troester
Summary: This study investigated the impact of intratumoral heterogeneity on the reproducibility of the PAM50 assay for breast cancer classification. The results showed that technical replicates achieved high agreement, but spatially distinct biological replicates had lower agreement. This suggests the presence of intratumoral heterogeneity in a small proportion of cases.
BREAST CANCER RESEARCH AND TREATMENT
(2023)
Article
Oncology
Nanor Sirab, Damien Drubay, Pascale Maille, Tatiana Popova, Carine Ngo, David Gentien, Anissa Moktefi, Pascale Soyeux-Porte, Romain Pelletier, Cecile Reyes, Emilie Henry, Damien Pouessel, Dimitri Vordos, Thierry Lebret, Aurelien de Reynies, Xavier Paoletti, Francois Radvanyi, Yves Allory
Summary: The study aimed to investigate intratumor heterogeneity in the Ba/Sq subtype of MIBC. The results showed multilayer heterogeneity in Ba/Sq tumors, including low and high levels of heterogeneity. This internal heterogeneity adds complexity to diagnosis and treatment decision-making.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Dharma Pally, Shyamili Goutham, Ramray Bhat
Summary: The architecture of an organ's cells and connective tissue is disrupted and replaced by new intercommunications between malignantly transformed parenchyma, altered stromal cells, and remodeled extracellular matrix (ECM) during tumorigenesis. The intratumoral heterogeneity of cancer cell phenotypes is an emergent property of these reciprocal intercommunications, both biochemical and mechanical-physical, which engender and amplify the diversity of cell behavioral traits.
Article
Oncology
Nathalie Faumont, Oussama Taoui, Davi Collares, Jean-Philippe Jais, Karen Leroy, Lea Prevaud, Fabrice Jardin, Thierry J. Molina, Christiane Copie-Bergman, Barbara Petit, Marie-Pierre Gourin, Dominique Bordessoule, Danielle Troutaud, Veronique Baud, Jean Feuillard
Summary: The relationship between c-Rel and GCB-DLBCLs was found to be closely associated, with c-Rel DNA-binding activity correlating with increased REL mRNA expression. Cases with a c-Rel signature exhibited better overall survival and c-Rel overexpression could directly promote DLBCL tumorigenesis.
FRONTIERS IN ONCOLOGY
(2021)
Article
Hematology
Baptiste Eluard, Stephanie Nuan-Aliman, Nathalie Faumont, Davi Collares, Didier Bordereaux, Aurelie Montagne, Isabelle Martins, Nicolas Cagnard, Martial Caly, Oussama Taoui, Leonardo Lordello, Jacqueline Lehmann-Che, Bruno Tesson, Jose-Angel Martinez-Climent, Christiane Copie-Bergman, Corinne Haioun, Herve Tilly, Benjamin Bonsang, Anne Vincent-Salomon, Jean-Philippe Jais, Fabrice Jardin, Karen Leroy, Maria Chiara Maiuri, Guido Kroemer, Thierry Jo Molina, Jean Feuillard, Veronique Baud
Summary: RelB activation is frequently observed in DLBCL and defines a new subset of patients with distinct gene expression profile and mutational pattern. RelB positivity is associated with poor prognosis after immunochemotherapy, and it confers resistance to doxorubicin-induced apoptosis in DLBCL cells.
Article
Oncology
Florence Koeppel, Etienne Muller, Alexandre Harle, Celine Guien, Pierre Sujobert, Olfa Trabelsi Grati, Olivier Kosmider, Laurent Miguet, Laurent Mauvieux, Anne Cayre, David Salgado, Claude Preudhomme, Lucie Karayan-Tapon, Gaelle Tachon, Florence Coulet, Alexandra Lespagnol, Christophe Beroud, Karen Leroy, Etienne Rouleau, Isabelle Soubeyran
Summary: To accurately interpret the pathogenicity of somatic variants in cancer, specific criteria such as disease and therapeutic context, co-occurring genomic events in the tumor, cancer-specific variant databases, and the gene role in tumorigenesis need to be considered. The proposed classification method could contribute to standardizing best practices and improving interpretation consistency.
EUROPEAN JOURNAL OF CANCER
(2021)
Article
Oncology
Guillaume Beinse, Marie-Aude Le Frere Belda, Pierre-Alexandre Just, Nahina Bekmezian, Meriem Koual, Simon Garinet, Karen Leroy, Franck Letourneur, Adele Lusson, Claire Mulot, Delphine Le Corre, Marie Metairie, Nicolas Delanoy, Helene Blons, Claire Gervais, Catherine Durdux, Charles Chapron, Francois Goldwasser, Benoit Terris, Cecile Badoual, Valerie Taly, Pierre Laurent-Puig, Bruno Borghese, Anne-Sophie Bats, Jerome Alexandre
Summary: This study aimed to evaluate the classification ability of RNA sequencing (RNA-seq) for prognosis prediction in endometrial carcinoma (EC) patients. The results showed that RNA-seq can provide additional prognostic information beyond established classification systems and has potential applications in therapeutic strategies for EC.
GYNECOLOGIC ONCOLOGY
(2022)
Article
Endocrinology & Metabolism
Lionel Groussin, Helene Theodon, Laura Bessiene, Leopoldine Bricaire, Fideline Bonnet-Serrano, Beatrix Cochand-Priollet, Karen Leroy, Simon Garinet, Eric Pasmant, Jeremie Zerbit, Romain Seban, Francois Goldwasser, Jerome Clerc, Anne Segolene Cottereau, Olivier Huillard
Summary: Inhibitors may treat RAI-resistant cancers by activating RAI and providing antitumoral effects, but not all patients experience redifferentiation.
Article
Medical Laboratory Technology
Guillaume Beinse, Bruno Borghese, Marie Metairie, Pierre-Alexandre Just, Geoffroy Poulet, Simon Garinet, Beatrice Parfait, Audrey Didelot, Camille Bourreau, Natacha Agueeff, Alexandre Lavolle, Benoit Terris, Charles Chapron, Francois Goldwasser, Karen Leroy, Helene Blons, Pierre Laurent-Puig, Valerie Taly, Jerome Alexandre
Summary: This study aimed to identify DNA positions universally hypermethylated in endometrial carcinoma (EC) and develop a digital droplet PCR (ddPCR) assay for detection of hypermethylated circulating tumor DNA (meth-ctDNA) in plasma from EC patients. The study found that methylation of ZSCAN12/OXT can be highly specific and sensitive in detecting ctDNA in plasma, providing promise for personalized approaches for EC patients.
CLINICAL CHEMISTRY
(2022)
Review
Oncology
Lola Paulet, Alexis Trecourt, Alexandra Leary, Julien Peron, Francoise Descotes, Mojgan Devouassoux-Shisheboran, Karen Leroy, Benoit You, Jonathan Lopez
Summary: DNA double-strand breaks are critical DNA damages for cells, and some cancers with homologous recombination deficiency (HRD) exhibit increased sensitivity to PARP inhibitors (PARPi). A major challenge is the development of tests capable of detecting HRD phenotype and predicting sensitivity to PARPi.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Endocrinology & Metabolism
Anne Jouinot, Juliane Lippert, Mathilde Sibony, Florian Violon, Lindsay Jeanpierre, Daniel De Murat, Roberta Armignacco, Amandine Septier, Karine Perlemoine, Franck Letourneur, Brigitte Izac, Bruno Ragazzon, Karen Leroy, Eric Pasmant, Marie-Odile North, Sebastien Gaujoux, Bertrand Dousset, Lionel Groussin, Rossella Libe, Benoit Terris, Martin Fassnacht, Cristina L. Ronchi, Jerome Bertherat, Guillaume Assie
Summary: This study demonstrates the use of the new 3'-end RNA-sequencing technology to determine molecular classification of adrenocortical tumors (ACT) from formalin-fixed paraffin-embedded (FFPE) samples. The results show that FFPE transcriptome has independent prognostic value and can distinguish different subtypes of ACT. Additionally, the technique is also applicable for studying rare oncocytic ACT variants.
EUROPEAN JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Oncology
Guillaume Beinse, Pierre-Alexandre Just, Marie-Aude Le Frere Belda, Pierre Laurent-Puig, Sebastien Jacques, Meriem Koual, Simon Garinet, Karen Leroy, Nicolas Delanoy, Helene Blons, Claire Gervais, Catherine Durdux, Charles Chapron, Francois Goldwasser, Benoit Terris, Cecile Badoual, Valerie Taly, Anne-Sophie Bats, Bruno Borghese, Jerome Alexandre
Summary: This study identified a common transcriptional profile shared by endometrial, breast, and ovarian cancers with homologous recombination deficiency (HRD). The RNAseq score derived from this profile was predictive of HRD and correlated with HRD in independent gynecological cancer datasets. The RNAseq HRD profile was associated with better overall survival in certain subtypes of these cancers and could potentially be used for prognostication and therapeutic decision-making.
BRITISH JOURNAL OF CANCER
(2022)
Review
Pharmacology & Pharmacy
Philippe Icard, Luca Simula, Ludovic Fournel, Karen Leroy, Audrey Lupo, Diane Damotte, Marie Christine Charpentier, Catherine Durdux, Mauro Loi, Olivier Schussler, Guillaume Chassagnon, Antoine Coquerel, Hubert Lincet, Vincent De Pauw, Marco Alifano
Summary: NSCLC is the main cause of cancer mortality and poses a significant challenge in cancer therapy. Resistance to anticancer drugs is promoted by hypoxia and HIF-1?? in tumor cells. Chemoresistance is also influenced by the activation of various oncogenic signaling pathways.
DRUG RESISTANCE UPDATES
(2022)
Article
Hematology
Vasiliki Papadopoulou, Jacqueline Schoumans, Ilaria Scarpelli, Sabine Blum
Summary: The gene encoding for transcription factor ETV6 frequently undergoes mutations in hematologic neoplasms. The role of ETV6 in normal hematopoiesis is unclear, but its loss of function may contribute to tumorigenesis. Deletions at the ETV6-locus (12p13) are rare but recurrent in myeloid neoplasms, while ETV6 translocations are even rarer but seem to have defining consequences on phenotype. The mechanisms underlying these lesions are still unknown.
ACTA HAEMATOLOGICA
(2023)
Letter
Pharmacology & Pharmacy
Vasiliki Papadopoulou, Nils Degrauwe, Laurent Arthur Decosterd, Thierry Buclin, Anne Cairoli
INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS
(2023)
Article
Hematology
Vasiliki Papadopoulou, Giulia Schiavini
Summary: In our clinical practice, we have consistently observed a prolongation of activated partial thromboplastin time (aPTT) in patients treated with asparaginase. However, this phenomenon is largely unreported in the literature and guidelines, and is not widely known to clinicians. In this study, we investigated the changes in clotting factors, fibrinogen, and D-dimers before and after asparaginase administration in a small cohort of patients. We found significant reductions in FIX and FXI levels after treatment, confirming previous observations. Our findings suggest that the prolonged aPTTs may be caused by disturbed factor synthesis rather than consumption.
JOURNAL OF BLOOD MEDICINE
(2023)
Article
Hematology
Vasiliki Papadopoulou, Jacqueline Schoumans, Valentin Basset, Francoise Solly, Jerome Pasquier, Sabine Blum, Olivier Spertini
Summary: Objective IDH1/2 mutations, intervening in epigenetic procedures, are frequently encountered in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). Knowledge of the genetics, immunophenotypes, and mutational kinetics of IDH1/2-mutated AML can contribute to the understanding of AML clonal architecture and inform therapeutics and monitoring.
Article
Oncology
Yoan Velut, Elise Decroix, Helene Blons, Marco Alifano, Karen Leroy, Florent Petitprez, Aurelie Boni, Simon Garinet, Jerome Biton, Isabelle Cremer, Marie Wislez, Pascaline Boudou-Rouquette, Jennifer Arrondeau, Francois Goldwasser, Ludovic Fournel, Diane Damotte, Audrey Mansuet-Lupo
Summary: SMARCA4/BRG1 loss is common in NSCLC and is associated with high-grade adenocarcinomas and pleomorphic carcinomas. SD-NSCLC patients have an immunosuppressive environment characterized by increased FOXP3+ cells and neutrophil densities. SD-NSCLC patients have a poor prognosis and limited response to PD1 inhibitors.
