Constraints in cancer evolution

2017 ◽  
Vol 45 (1) ◽  
pp. 1-13 ◽  
Author(s):  
Subramanian Venkatesan ◽  
Nicolai J. Birkbak ◽  
Charles Swanton

Next-generation deep genome sequencing has only recently allowed us to quantitatively dissect the extent of heterogeneity within a tumour, resolving patterns of cancer evolution. Intratumour heterogeneity and natural selection contribute to resistance to anticancer therapies in the advanced setting. Recent evidence has also revealed that cancer evolution might be constrained. In this review, we discuss the origins of intratumour heterogeneity and subsequently focus on constraints imposed upon cancer evolution. The presence of (1) parallel evolution, (2) convergent evolution and (3) the biological impact of acquiring mutations in specific orders suggest that cancer evolution may be exploitable. These constraints on cancer evolution may help us identify cancer evolutionary rule books, which could eventually inform both diagnostic and therapeutic approaches to improve survival outcomes.

BMC Genomics ◽  
2015 ◽  
Vol 16 (1) ◽  
Author(s):  
Chi Keung Cheng ◽  
Man Kit Cheung ◽  
Wenyan Nong ◽  
Patrick Tik Wan Law ◽  
Jing Qin ◽  
...  

Author(s):  
Giulio Caravagna

AbstractCancers progress through the accumulation of somatic mutations which accrue during tumour evolution, allowing some cells to proliferate in an uncontrolled fashion. This growth process is intimately related to latent evolutionary forces moulding the genetic and epigenetic composition of tumour subpopulations. Understanding cancer requires therefore the understanding of these selective pressures. The adoption of widespread next-generation sequencing technologies opens up for the possibility of measuring molecular profiles of cancers at multiple resolutions, across one or multiple patients. In this review we discuss how cancer genome sequencing data from a single tumour can be used to understand these evolutionary forces, overviewing mathematical models and inferential methods adopted in field of Cancer Evolution.


2019 ◽  
Vol 24 (2) ◽  
Author(s):  
Anja Berger ◽  
Alexandra Dangel ◽  
Tilmann Schober ◽  
Birgit Schmidbauer ◽  
Regina Konrad ◽  
...  

In September 2018, a child who had returned from Somalia to Germany presented with cutaneous diphtheria by toxigenic Corynebacterium diphtheriae biovar mitis. The child’s sibling had superinfected insect bites harbouring also toxigenic C. diphtheriae. Next generation sequencing (NGS) revealed the same strain in both patients suggesting very recent human-to-human transmission. Epidemiological and NGS data suggest that the two cutaneous diphtheria cases constitute the first outbreak by toxigenic C. diphtheriae in Germany since the 1980s.


2018 ◽  
Vol 4 (suppl_1) ◽  
Author(s):  
T Iketleng ◽  
T Mogashoa ◽  
B Mbeha ◽  
L Letsibogo ◽  
J Makhema ◽  
...  

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 357 ◽  
Author(s):  
Carmelo Gurnari ◽  
Maria Teresa Voso ◽  
Jaroslaw P. Maciejewski ◽  
Valeria Visconte

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatment. A specific focus will be given to molecularly targeted therapies for AML as a representation of possible agents for precision medicine. We will discuss experimental and preclinical data for FLT3, IDH1, BCL-2, Hedgehog pathway inhibitors, and epitherapy.


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