Santiago Ramón y Cajal

S. Bullman, C. Pedamallu, E. Sicinska, T. Clancy, Xiaoyang Zhang, D. Cai, D. Neuberg, Katherine Huang, F. Guevara, T. Nelson, Otari Chipashvili, Timothy Hagan, M. Walker, A. Ramachandran, B. Diosdado, G. Serna, N. Mulet, S. Landolfi, S. Ramón y. Cajal, R. Fasani, A. Aguirre, K. Ng, E. Élez, S. Ogino, J. Tabernero, C. Fuchs, W. Hahn, P. Nuciforo, M. Meyerson

Bacteria go the distance in cancer The bacterial species Fusobacterium nucleatum is associated with a subset of human colorectal cancers, but its role in tumorigenesis is unclear. Studying patient samples, Bullman et al. found that F. nucleatum and certain co-occurring bacteria were present not only in primary tumors but also in distant metastases. Preliminary evidence suggests that the bacterium is localized primarily within the metastatic cancer cells rather than in the stroma. Antibiotic treatment of mice carrying xenografts of F. nucleatum–positive human colorectal cancer slowed tumor growth, consistent with a causal role for the bacterium in tumorigenesis. Science, this issue p. 1443 The same bacteria present in primary tumors of patients with colorectal cancer are also present in liver metastases. Colorectal cancers comprise a complex mixture of malignant cells, nontransformed cells, and microorganisms. Fusobacterium nucleatum is among the most prevalent bacterial species in colorectal cancer tissues. Here we show that colonization of human colorectal cancers with Fusobacterium and its associated microbiome—including Bacteroides, Selenomonas, and Prevotella species—is maintained in distal metastases, demonstrating microbiome stability between paired primary and metastatic tumors. In situ hybridization analysis revealed that Fusobacterium is predominantly associated with cancer cells in the metastatic lesions. Mouse xenografts of human primary colorectal adenocarcinomas were found to retain viable Fusobacterium and its associated microbiome through successive passages. Treatment of mice bearing a colon cancer xenograft with the antibiotic metronidazole reduced Fusobacterium load, cancer cell proliferation, and overall tumor growth. These observations argue for further investigation of antimicrobial interventions as a potential treatment for patients with Fusobacterium-associated colorectal cancer.

M. Scaltriti, F. Rojo, A. Ocaña, J. Anido, M. Guzman, J. Cortés, S. Di Cosimo, X. Matías-Guiu, S. Ramón y. Cajal, J. Arribas, J. Baselga

L. De Mattos-Arruda, R. Mayor, C. Ng, B. Weigelt, F. Martínez-Ricarte, D. Torrejon, Mafalda Oliveira, A. Arias, C. Raventós, Jiabin Tang, Elena Guerini‐Rocco, E. Martínez-Sáez, Sergio Lois, Òscar Marín, X. de la Cruz, S. Piscuoglio, Russell Towers, A. Vivancos, V. Peg, S. Ramón y. Cajal, J. Carles, J. Rodón, M. González-Cao, J. Tabernero, E. Felip, J. Sahuquillo, M. Berger, J. Cortés, J. Reis-Filho, J. Seoane

Cell-free circulating tumour DNA (ctDNA) in plasma has been shown to be informative of the genomic alterations present in tumours and has been used to monitor tumour progression and response to treatments. However, patients with brain tumours do not present with or present with low amounts of ctDNA in plasma precluding the genomic characterization of brain cancer through plasma ctDNA. Here we show that ctDNA derived from central nervous system tumours is more abundantly present in the cerebrospinal fluid (CSF) than in plasma. Massively parallel sequencing of CSF ctDNA more comprehensively characterizes the genomic alterations of brain tumours than plasma, allowing the identification of actionable brain tumour somatic mutations. We show that CSF ctDNA levels longitudinally fluctuate in time and follow the changes in brain tumour burden providing biomarkers to monitor brain malignancies. Moreover, CSF ctDNA is shown to facilitate and complement the diagnosis of leptomeningeal carcinomatosis. DNA circulating in the plasma of cancer patients carries features of the primary tumour, however such DNA is found in low levels in brain cancer patients. Here, the authors show that circulating tumour DNA can be detected in the cerebral spinal fluid of cancer patients and that this better recapitulates the primary tumour compared to DNA from the plasma.

C. Romagosa, S. Simonetti, Laura López-Vicente, A. Mazo, M. Lleonart, J. Castellví, S. Y. Cajal

M. Scaltriti, C. Verma, M. Guzmán, J. Jiménez, J. Parra, Kim Pedersen, Derek Smith, S. Landolfi, S. Y. Cajal, J. Arribas, José Baselga, José Baselga