Now showing items 1-20 of 44

    • A Big Bang model of human colorectal tumor growth. 

      Sottoriva, A; Kang, H; Ma, Z; Graham, TA; Salomon, MP; Zhao, J; Marjoram, P; Siegmund, K; Press, MF; Shibata, D; Curtis, C (2015-03)
      What happens in early, still undetectable human malignancies is unknown because direct observations are impractical. Here we present and validate a 'Big Bang' model, whereby tumors grow predominantly as a single expansion ...
    • Analysis of tumour ecological balance reveals resource-dependent adaptive strategies of ovarian cancer. 

      Nawaz, S; Trahearn, NA; Heindl, A; Banerjee, S; Maley, CC; Sottoriva, A; Yuan, Y (2019-10-21)
      BACKGROUND:Despite treatment advances, there remains a significant risk of recurrence in ovarian cancer, at which stage it is usually incurable. Consequently, there is a clear need for improved patient stratification. ...
    • Between-region genetic divergence reflects the mode and tempo of tumor evolution. 

      Sun, R; Hu, Z; Sottoriva, A; Graham, TA; Harpak, A; Ma, Z; Fischer, JM; Shibata, D; Curtis, C (2017-07)
      Given the implications of tumor dynamics for precision medicine, there is a need to systematically characterize the mode of evolution across diverse solid tumor types. In particular, methods to infer the role of natural ...
    • Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer. 

      Lote, H; Spiteri, I; Ermini, L; Vatsiou, A; Roy, A; McDonald, A; Maka, N; Balsitis, M; Bose, N; Simbolo, M; Mafficini, A; Lampis, A; Hahne, JC; Trevisani, F; Eltahir, Z; Mentrasti, G; Findlay, C; Kalkman, EAJ; Punta, M; Werner, B; Lise, S; Aktipis, A; Maley, C; Greaves, M; Braconi, C; White, J; Fassan, M; Scarpa, A; Sottoriva, A; Valeri, N
      Background: Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but ...
    • Carbon dating cancer: defining the chronology of metastatic progression in colorectal cancer. 

      Lote, H; Spiteri, I; Ermini, L; Vatsiou, A; Roy, A; McDonald, A; Maka, N; Balsitis, M; Bose, N; Simbolo, M; Mafficini, A; Lampis, A; Hahne, JC; Trevisani, F; Eltahir, Z; Mentrasti, G; Findlay, C; Kalkman, EAJ; Punta, M; Werner, B; Lise, S; Aktipis, A; Maley, C; Greaves, M; Braconi, C; White, J; Fassan, M; Scarpa, A; Sottoriva, A; Valeri, N (2017-06)
      Background Patients often ask oncologists how long a cancer has been present before causing symptoms or spreading to other organs. The evolutionary trajectory of cancers can be defined using phylogenetic approaches but ...
    • Catch my drift? Making sense of genomic intra-tumour heterogeneity. 

      Sottoriva, A; Barnes, CP; Graham, TA (2017-04)
      The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two components, the role of drift in cancer evolution has received ...
    • Classifying the evolutionary and ecological features of neoplasms. 

      Maley, CC; Aktipis, A; Graham, TA; Sottoriva, A; Boddy, AM; Janiszewska, M; Silva, AS; Gerlinger, M; Yuan, Y; Pienta, KJ; Anderson, KS; Gatenby, R; Swanton, C; Posada, D; Wu, C-I; Schiffman, JD; Hwang, ES; Polyak, K; Anderson, ARA; Brown, JS; Greaves, M; Shibata, D (2017-10)
      Neoplasms change over time through a process of cell-level evolution, driven by genetic and epigenetic alterations. However, the ecology of the microenvironment of a neoplastic cell determines which changes provide adaptive ...
    • Colorectal cancer residual disease at maximal response to EGFR blockade displays a druggable Paneth cell-like phenotype. 

      Lupo, B; Sassi, F; Pinnelli, M; Galimi, F; Zanella, ER; Vurchio, V; Migliardi, G; Gagliardi, PA; Puliafito, A; Manganaro, D; Luraghi, P; Kragh, M; Pedersen, MW; Horak, ID; Boccaccio, C; Medico, E; Primo, L; Nichol, D; Spiteri, I; Heide, T; Vatsiou, A; Graham, TA; Élez, E; Argiles, G; Nuciforo, P; Sottoriva, A; Dienstmann, R; Pasini, D; Grassi, E; Isella, C; Bertotti, A; Trusolino, L (2020-08)
      Blockade of epidermal growth factor receptor (EGFR) causes tumor regression in some patients with metastatic colorectal cancer (mCRC). However, residual disease reservoirs typically remain even after maximal response to ...
    • Contributions to drug resistance in glioblastoma derived from malignant cells in the sub-ependymal zone. 

      Piccirillo, SG; Spiteri, I; Sottoriva, A; Touloumis, A; Ber, S; Price, SJ; Heywood, R; Francis, N-J; Howarth, KD; Collins, VP; Venkitaraman, AR; Curtis, C; Marioni, JC; Tavaré, S; Watts, C (2015-01)
      Glioblastoma, the most common and aggressive adult brain tumor, is characterized by extreme phenotypic diversity and treatment failure. Through fluorescence-guided resection, we identified fluorescent tissue in the ...
    • Detecting repeated cancer evolution in human tumours from multi-region sequencing data 

      Caravagna, G; Giarratano, Y; Ramazzotti, D; Graham, T; Sanguinetti, G; Sottoriva, A (2017-06-27)
      Carcinogenesis is an evolutionary process driven by the accumulation of genomic aberrations. Recurrent sequences of genomic changes, both between and within patients, reflect repeated evolution that is valuable for ...
    • Detecting truly clonal alterations from multi-region profiling of tumours. 

      Werner, B; Traulsen, A; Sottoriva, A; Dingli, D (2017-03-27)
      Modern cancer therapies aim at targeting tumour-specific alterations, such as mutations or neo-antigens, and maximal treatment efficacy requires that targeted alterations are present in all tumour cells. Currently, treatment ...
    • Divergent adaptation in thyroid cancers. 

      Sottoriva, A (2018-06)
    • EGFR amplification and outcome in a randomised phase III trial of chemotherapy alone or chemotherapy plus panitumumab for advanced gastro-oesophageal cancers. 

      Smyth, EC; Vlachogiannis, G; Hedayat, S; Harbery, A; Hulkki-Wilson, S; Salati, M; Kouvelakis, K; Fernandez-Mateos, J; Cresswell, GD; Fontana, E; Seidlitz, T; Peckitt, C; Hahne, JC; Lampis, A; Begum, R; Watkins, D; Rao, S; Starling, N; Waddell, T; Okines, A; Crosby, T; Mansoor, W; Wadsley, J; Middleton, G; Fassan, M; Wotherspoon, A; Braconi, C; Chau, I; Vivanco, I; Sottoriva, A; Stange, DE; Cunningham, D; Valeri, N (2020-11-16)
      Objective Epidermal growth factor receptor (EGFR) inhibition may be effective in biomarker-selected populations of advanced gastro-oesophageal adenocarcinoma (aGEA) patients. Here, we tested the association between outcome ...
    • Evolutionary dynamics of neoantigens in growing tumors. 

      Lakatos, E; Williams, MJ; Schenck, RO; Cross, WCH; Househam, J; Zapata, L; Werner, B; Gatenbee, C; Robertson-Tessi, M; Barnes, CP; Anderson, ARA; Sottoriva, A; Graham, TA (2020-10)
      Cancers accumulate mutations that lead to neoantigens, novel peptides that elicit an immune response, and consequently undergo evolutionary selection. Here we establish how negative selection shapes the clonality of ...
    • Evolutionary dynamics of residual disease in human glioblastoma. 

      Spiteri, I; Caravagna, G; Cresswell, GD; Vatsiou, A; Nichol, D; Acar, A; Ermini, L; Chkhaidze, K; Werner, B; Mair, R; Brognaro, E; Verhaak, RGW; Sanguinetti, G; Piccirillo, SGM; Watts, C; Sottoriva, A (2019-03)
      Background Glioblastoma is the most common and aggressive adult brain malignancy against which conventional surgery and chemoradiation provide limited benefit. Even when a good treatment response is obtained, recurrence ...
    • Exploiting evolutionary steering to induce collateral drug sensitivity in cancer. 

      Acar, A; Nichol, D; Fernandez-Mateos, J; Cresswell, GD; Barozzi, I; Hong, SP; Trahearn, N; Spiteri, I; Stubbs, M; Burke, R; Stewart, A; Caravagna, G; Werner, B; Vlachogiannis, G; Maley, CC; Magnani, L; Valeri, N; Banerji, U; Sottoriva, A (2020-04-21)
      Drug resistance mediated by clonal evolution is arguably the biggest problem in cancer therapy today. However, evolving resistance to one drug may come at a cost of decreased fecundity or increased sensitivity to another ...
    • Functional versus non-functional intratumor heterogeneity in cancer. 

      Williams, MJ; Werner, B; Graham, TA; Sottoriva, A (2016-07)
      Next-generation sequencing data from human cancers are often difficult to interpret within the context of tumor evolution. We developed a mathematical model describing the accumulation of mutations under neutral evolutionary ...
    • Identification of neutral tumor evolution across cancer types. 

      Williams, MJ; Werner, B; Barnes, CP; Graham, TA; Sottoriva, A (2016-03)
      Despite extraordinary efforts to profile cancer genomes, interpreting the vast amount of genomic data in the light of cancer evolution remains challenging. Here we demonstrate that neutral tumor evolution results in a ...
    • Intratumor heterogeneity in human glioblastoma reflects cancer evolutionary dynamics. 

      Sottoriva, A; Spiteri, I; Piccirillo, SGM; Touloumis, A; Collins, VP; Marioni, JC; Curtis, C; Watts, C; Tavaré, S (2013-03)
      Glioblastoma (GB) is the most common and aggressive primary brain malignancy, with poor prognosis and a lack of effective therapeutic options. Accumulating evidence suggests that intratumor heterogeneity likely is the key ...
    • Longitudinal Liquid Biopsy and Mathematical Modeling of Clonal Evolution Forecast Time to Treatment Failure in the PROSPECT-C Phase II Colorectal Cancer Clinical Trial. 

      Khan, KH; Cunningham, D; Werner, B; Vlachogiannis, G; Spiteri, I; Heide, T; Mateos, JF; Vatsiou, A; Lampis, A; Damavandi, MD; Lote, H; Huntingford, IS; Hedayat, S; Chau, I; Tunariu, N; Mentrasti, G; Trevisani, F; Rao, S; Anandappa, G; Watkins, D; Starling, N; Thomas, J; Peckitt, C; Khan, N; Rugge, M; Begum, R; Hezelova, B; Bryant, A; Jones, T; Proszek, P; Fassan, M; Hahne, JC; Hubank, M; Braconi, C; Sottoriva, A; Valeri, N (2018-10)
      Sequential profiling of plasma cell-free DNA (cfDNA) holds immense promise for early detection of patient progression. However, how to exploit the predictive power of cfDNA as a liquid biopsy in the clinic remains unclear. ...