---
OA_place: publisher
_id: '1400'
abstract:
- lang: eng
  text: Cancer results from an uncontrolled growth of abnormal cells. Sequentially
    accumulated genetic and epigenetic alterations decrease cell death and increase
    cell replication. We used mathematical models to quantify the effect of driver
    gene mutations. The recently developed targeted therapies can lead to dramatic
    regressions. However, in solid cancers, clinical responses are often short-lived
    because resistant cancer cells evolve. We estimated that approximately 50 different
    mutations can confer resistance to a typical targeted therapeutic agent. We find
    that resistant cells are likely to be present in expanded subclones before the
    start of the treatment. The dominant strategy to prevent the evolution of resistance
    is combination therapy. Our analytical results suggest that in most patients,
    dual therapy, but not monotherapy, can result in long-term disease control. However,
    long-term control can only occur if there are no possible mutations in the genome
    that can cause cross-resistance to both drugs. Furthermore, we showed that simultaneous
    therapy with two drugs is much more likely to result in long-term disease control
    than sequential therapy with the same drugs. To improve our understanding of the
    underlying subclonal evolution we reconstruct the evolutionary history of a patient's
    cancer from next-generation sequencing data of spatially-distinct DNA samples.
    Using a quantitative measure of genetic relatedness, we found that pancreatic
    cancers and their metastases demonstrated a higher level of relatedness than that
    expected for any two cells randomly taken from a normal tissue. This minimal amount
    of genetic divergence among advanced lesions indicates that genetic heterogeneity,
    when quantitatively defined, is not a fundamental feature of the natural history
    of untreated pancreatic cancers. Our newly developed, phylogenomic tool Treeomics
    finds evidence for seeding patterns of metastases and can directly be used to
    discover rules governing the evolution of solid malignancies to transform cancer
    into a more predictable disease.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Johannes
  full_name: Reiter, Johannes
  id: 4A918E98-F248-11E8-B48F-1D18A9856A87
  last_name: Reiter
  orcid: 0000-0002-0170-7353
citation:
  ama: Reiter J. The subclonal evolution of cancer. 2015.
  apa: Reiter, J. (2015). <i>The subclonal evolution of cancer</i>. Institute of Science
    and Technology Austria.
  chicago: Reiter, Johannes. “The Subclonal Evolution of Cancer.” Institute of Science
    and Technology Austria, 2015.
  ieee: J. Reiter, “The subclonal evolution of cancer,” Institute of Science and Technology
    Austria, 2015.
  ista: Reiter J. 2015. The subclonal evolution of cancer. Institute of Science and
    Technology Austria.
  mla: Reiter, Johannes. <i>The Subclonal Evolution of Cancer</i>. Institute of Science
    and Technology Austria, 2015.
  short: J. Reiter, The Subclonal Evolution of Cancer, Institute of Science and Technology
    Austria, 2015.
corr_author: '1'
date_created: 2018-12-11T11:51:48Z
date_published: 2015-04-01T00:00:00Z
date_updated: 2026-04-09T14:26:24Z
day: '01'
degree_awarded: PhD
department:
- _id: KrCh
language:
- iso: eng
month: '04'
oa_version: None
page: '183'
publication_identifier:
  issn:
  - 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
publist_id: '5807'
related_material:
  record:
  - id: '2000'
    relation: part_of_dissertation
    status: public
  - id: '1709'
    relation: part_of_dissertation
    status: public
  - id: '2858'
    relation: part_of_dissertation
    status: public
  - id: '2816'
    relation: part_of_dissertation
    status: public
  - id: '2247'
    relation: part_of_dissertation
    status: public
  - id: '3260'
    relation: part_of_dissertation
    status: public
  - id: '3157'
    relation: part_of_dissertation
    status: public
status: public
supervisor:
- first_name: Krishnendu
  full_name: Chatterjee, Krishnendu
  id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
  last_name: Chatterjee
  orcid: 0000-0002-4561-241X
title: The subclonal evolution of cancer
type: dissertation
user_id: ba8df636-2132-11f1-aed0-ed93e2281fdd
year: '2015'
...