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Targeting cancer evolution in the clinic

Guest Editors: Razelle Kurzrock and Alberto Bardelli

New Content ItemGenome Medicine is pleased to present a special issue on ‘Targeting cancer evolution in the clinic,’ guest-edited by Dr. Razelle Kurzrock from the University of San Diego and Dr. Alberto Bardelli from the University of Torino. Progress in the understanding of cancer evolution, heterogeneity, and metastasis has accelerated in recent years due in large part to advancements in sequencing technology. The advent of massively parallel sequencing has encouraged extensive tumor mutational profiling efforts, mapping of cancer genomic landscapes, and widespread tracking of genomes longitudinally from cancer development, to metastasis, and eventually to therapeutic response and resistance. Particularly intriguing are attempts to translate these insights into the clinic, where they can be utilized for precision medicine from prevention, risk prediction and early detection, to therapeutic targeting, longitudinal monitoring, and prognosis. The tracking of clonal dynamics to determine driver mutations, monitor potential resistant subpopulations, and gauge response to therapy represents a promising strategy for clinical cancer medicine. 

This special issue aims to capture advances in this growing area, covering the breadth of cancer evolution and clinical cancer therapeutics including clonal evolution and dynamics, tumor heterogeneity and clonal diversity, metastases, precision medicine and therapeutics, longitudinal monitoring, and treatment response and clonal resistance.

This collection of articles has not been sponsored and articles will undergo the journal’s standard peer-review process. The Guest Editors declare that they have no competing interests. Guest Editors serve an advisory role to guide the scope of the special issue and commissioned content; final editorial decisions lie with the Editor.

  1. Subclonal evolution during primary breast cancer treatment is largely unexplored. We aimed to assess the dynamic changes in subclonal composition of treatment-naïve breast cancers during neoadjuvant chemotherapy.

    Authors: Andreas Venizelos, Christina Engebrethsen, Wei Deng, Jürgen Geisler, Stephanie Geisler, Gjertrud T. Iversen, Turid Aas, Hildegunn S. Aase, Manouchehr Seyedzadeh, Eli Sihn Steinskog, Ola Myklebost, Sigve Nakken, Daniel Vodak, Eivind Hovig, Leonardo A. Meza-Zepeda, Per E. Lønning…
    Citation: Genome Medicine 2022 14:86
  2. Immune checkpoint inhibitor (ICI) therapy has revolutionized the treatment of many cancers. However, the limited population that benefits from ICI therapy makes it necessary to screen predictive biomarkers for...

    Authors: Junyu Long, Dongxu Wang, Anqiang Wang, Peipei Chen, Yu Lin, Jin Bian, Xu Yang, Mingjun Zheng, Haohai Zhang, Yongchang Zheng, Xinting Sang and Haitao Zhao
    Citation: Genome Medicine 2022 14:20
  3. Lung adenocarcinoma, the most common type of lung cancer, has a high level of morphologic heterogeneity and is composed of tumor cells of multiple histological subtypes. It has been reported that immune cell i...

    Authors: Thinh T. Nguyen, Hyun-Sung Lee, Bryan M. Burt, Jia Wu, Jianjun Zhang, Christopher I. Amos and Chao Cheng
    Citation: Genome Medicine 2022 14:5
  4. Endometrial cancer (EC) is a major gynecological cancer with increasing incidence. It comprises four molecular subtypes with differing etiology, prognoses, and responses to chemotherapy. In the future, clinica...

    Authors: Vanessa F. Bonazzi, Olga Kondrashova, Deborah Smith, Katia Nones, Asmerom T. Sengal, Robert Ju, Leisl M. Packer, Lambros T. Koufariotis, Stephen H. Kazakoff, Aimee L. Davidson, Priya Ramarao-Milne, Vanessa Lakis, Felicity Newell, Rebecca Rogers, Claire Davies, James Nicklin…
    Citation: Genome Medicine 2022 14:3
  5. While understanding molecular heterogeneity across patients underpins precision oncology, there is increasing appreciation for taking intra-tumor heterogeneity into account. Based on large-scale analysis of ca...

    Authors: Chayaporn Suphavilai, Shumei Chia, Ankur Sharma, Lorna Tu, Rafael Peres Da Silva, Aanchal Mongia, Ramanuj DasGupta and Niranjan Nagarajan
    Citation: Genome Medicine 2021 13:189
  6. We present Beyondcell, a computational methodology for identifying tumour cell subpopulations with distinct drug responses in single-cell RNA-seq data and proposing cancer-specific treatments. Our method calcu...

    Authors: Coral Fustero-Torre, María José Jiménez-Santos, Santiago García-Martín, Carlos Carretero-Puche, Luis García-Jimeno, Vadym Ivanchuk, Tomás Di Domenico, Gonzalo Gómez-López and Fátima Al-Shahrour
    Citation: Genome Medicine 2021 13:187
  7. Cancer is a somatic evolutionary disease and adenocarcinomas of the stomach and gastroesophageal junction (GC) may serve as a two-dimensional model of cancer expansion, in which tumor subclones are not evenly ...

    Authors: Christoph Röcken, Anu Amallraja, Christine Halske, Luka Opasic, Arne Traulsen, Hans-Michael Behrens, Sandra Krüger, Anne Liu, Jochen Haag, Jan-Hendrik Egberts, Philip Rosenstiel and Tobias Meißner
    Citation: Genome Medicine 2021 13:177
  8. Metastatic breast cancer is a deadly disease with a low 5-year survival rate. Tracking metastatic spread in living patients is difficult and thus poorly understood.

    Authors: Xiaomeng Huang, Yi Qiao, Samuel W. Brady, Rachel E. Factor, Erinn Downs-Kelly, Andrew Farrell, Jasmine A. McQuerry, Gajendra Shrestha, David Jenkins, W. Evan Johnson, Adam L. Cohen, Andrea H. Bild and Gabor T. Marth
    Citation: Genome Medicine 2021 13:170
  9. Liver cancer is one of the most commonly diagnosed cancers and the fourth leading cause of cancer-related death worldwide. Broad-spectrum kinase inhibitors like sorafenib and lenvatinib provide only modest sur...

    Authors: Yuchen Guo, Jun Wang, Bente Benedict, Chen Yang, Frank van Gemert, Xuhui Ma, Dongmei Gao, Hui Wang, Shu Zhang, Cor Lieftink, Roderick L. Beijersbergen, Hein te Riele, Xiaohang Qiao, Qiang Gao, Chong Sun, Wenxin Qin…
    Citation: Genome Medicine 2021 13:166
  10. Tumor mutational burden (TMB) may be a predictive biomarker of immune checkpoint inhibitor (ICI) responsiveness. Genomic landscape heterogeneity is a well-established cancer feature. Molecular characteristics ...

    Authors: Timothy V. Pham, Aaron M. Goodman, Smruthy Sivakumar, Garrett Frampton and Razelle Kurzrock
    Citation: Genome Medicine 2021 13:159
  11. Malignancies are molecularly complex and become more resistant with each line of therapy. We hypothesized that offering matched, individualized combination therapies to patients with treatment-naïve, advanced ...

    Authors: Jason K. Sicklick, Shumei Kato, Ryosuke Okamura, Hitendra Patel, Mina Nikanjam, Paul T. Fanta, Michael E. Hahn, Pradip De, Casey Williams, Jessica Guido, Benjamin M. Solomon, Rana R. McKay, Amy Krie, Sarah G. Boles, Jeffrey S. Ross, J. Jack Lee…
    Citation: Genome Medicine 2021 13:155
  12. Epstein-Barr virus (EBV)-associated gastric carcinomas (EBVaGCs) present unique molecular signatures, but the tumorigenesis of EBVaGCs and the role EBV plays during this process remain poorly understood.

    Authors: Zhang-Hua Chen, Shu-Mei Yan, Xi-Xi Chen, Qi Zhang, Shang-Xin Liu, Yang Liu, Yi-Ling Luo, Chao Zhang, Miao Xu, Yi-Fan Zhao, Li-Yun Huang, Bin-Liu Liu, Tian-Liang Xia, Da-Zhi Xu, Yao Liang, Yong-Ming Chen…
    Citation: Genome Medicine 2021 13:146
  13. We developed a sensitive sequencing approach that simultaneously profiles microsatellite instability, chromosomal instability, and subclonal structure in cancer. We assessed diverse repeat motifs across 225 mi...

    Authors: GiWon Shin, Stephanie U. Greer, Erik Hopmans, Susan M. Grimes, HoJoon Lee, Lan Zhao, Laura Miotke, Carlos Suarez, Alison F. Almeda, Sigurdis Haraldsdottir and Hanlee P. Ji
    Citation: Genome Medicine 2021 13:145
  14. Gene expression-based subtyping has the potential to form a new paradigm for stratified treatment of colorectal cancer. However, current frameworks are based on the transcriptomic profiles of primary tumors, a...

    Authors: Seyed H. Moosavi, Peter W. Eide, Ina A. Eilertsen, Tuva H. Brunsell, Kaja C. G. Berg, Bård I. Røsok, Kristoffer W. Brudvik, Bjørn A. Bjørnbeth, Marianne G. Guren, Arild Nesbakken, Ragnhild A. Lothe and Anita Sveen
    Citation: Genome Medicine 2021 13:143
  15. Colorectal cancer is the 2nd leading cause of cancer-related deaths with few patients benefiting from biomarker-guided therapy. Mutation expression is essential for accurate interpretation of mutations as biom...

    Authors: Anita Sveen, Bjarne Johannessen, Ina A. Eilertsen, Bård I. Røsok, Marie Gulla, Peter W. Eide, Jarle Bruun, Kushtrim Kryeziu, Leonardo A. Meza-Zepeda, Ola Myklebost, Bjørn A. Bjørnbeth, Rolf I. Skotheim, Arild Nesbakken and Ragnhild A. Lothe
    Citation: Genome Medicine 2021 13:142
  16. The enrichment of Gram-negative bacteria of oral origin in the esophageal microbiome has been associated with the development of metaplasia. However, to date, no study has comprehensively assessed the relation...

    Authors: Nandan P. Deshpande, Stephen M. Riordan, Claire J. Gorman, Shaun Nielsen, Tonia L. Russell, Carolina Correa-Ospina, Bentotage S. M. Fernando, Shafagh A. Waters, Natalia Castaño-Rodríguez, Si Ming Man, Nicodemus Tedla, Marc R. Wilkins and Nadeem O. Kaakoush
    Citation: Genome Medicine 2021 13:133
  17. Tumor response to therapy is affected by both the cell types and the cell states present in the tumor microenvironment. This is true for many cancer treatments, including immune checkpoint inhibitors (ICIs). W...

    Authors: Emily F. Davis-Marcisak, Allison A. Fitzgerald, Michael D. Kessler, Ludmila Danilova, Elizabeth M. Jaffee, Neeha Zaidi, Louis M. Weiner and Elana J. Fertig
    Citation: Genome Medicine 2021 13:129
  18. Cancer evolution depends on epigenetic and genetic diversity. Historically, in multiple myeloma (MM), subclonal diversity and tumor evolution have been investigated mostly from a genetic perspective.

    Authors: Jennifer Derrien, Catherine Guérin-Charbonnel, Victor Gaborit, Loïc Campion, Magali Devic, Elise Douillard, Nathalie Roi, Hervé Avet-Loiseau, Olivier Decaux, Thierry Facon, Jan-Philipp Mallm, Roland Eils, Nikhil C. Munshi, Philippe Moreau, Carl Herrmann, Florence Magrangeas…
    Citation: Genome Medicine 2021 13:127
  19. The development of secondary resistance (SR) in metastatic colorectal cancer (mCRC) treated with anti-epidermal growth factor receptor (anti-EGFR) antibodies is not fully understood at the molecular level. Her...

    Authors: Deepak Vangala, Swetlana Ladigan, Sven T. Liffers, Soha Noseir, Abdelouahid Maghnouj, Tina-Maria Götze, Berlinda Verdoodt, Susanne Klein-Scory, Laura Godfrey, Martina K. Zowada, Mario Huerta, Daniel L. Edelstein, Jaime Martinez de Villarreal, Miriam Marqués, Jörg Kumbrink, Andreas Jung…
    Citation: Genome Medicine 2021 13:116
  20. Malignant pleural mesothelioma (MPM) is a heterogeneous cancer. Better knowledge of molecular and cellular intra-tumor heterogeneity throughout the thoracic cavity is required to develop efficient therapies. T...

    Authors: Clément Meiller, François Montagne, Theo Z. Hirsch, Stefano Caruso, Julien de Wolf, Quentin Bayard, Jean-Baptiste Assié, Léa Meunier, Yuna Blum, Lisa Quetel, Laure Gibault, Ecaterina Pintilie, Cécile Badoual, Sarah Humez, Françoise Galateau-Sallé, Marie-Christine Copin…
    Citation: Genome Medicine 2021 13:113