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Landscaping the cell surface proteome of breast cancer : Following pathways through organelles to the plasma membrane

Kurbasic, Emila LU (2017)
Abstract
Breast cancer is one of the most common cancers in women. It is most commonly treated by the surgical removal
of the tumour in combination with (neo)-adjuvant therapy (hormone, chemo- or radio- therapy before or after
surgery). However, a large number of patients are over treated, with approximately 60% being given adjuvant
therapy when already cured by surgery alone. This causes many undesirable side effects and cost hence, there is
great need for new diagnostic and prognostic methods to decide if patients are in need of adjuvant therapy.
A number of prognostic and treatment predictive factors have been established such as tumour size, hormone
receptor status, histological grade and age. Hereditary... (More)
Breast cancer is one of the most common cancers in women. It is most commonly treated by the surgical removal
of the tumour in combination with (neo)-adjuvant therapy (hormone, chemo- or radio- therapy before or after
surgery). However, a large number of patients are over treated, with approximately 60% being given adjuvant
therapy when already cured by surgery alone. This causes many undesirable side effects and cost hence, there is
great need for new diagnostic and prognostic methods to decide if patients are in need of adjuvant therapy.
A number of prognostic and treatment predictive factors have been established such as tumour size, hormone
receptor status, histological grade and age. Hereditary predisposition to developing cancer can be a factor, with
several high penetrance genes identified such as BRCA1 and BRCA2 genes as well as many as a dozen lower
risk genes that are however additive in effect. Molecular subtyping has significant prognostic value allowing the
differentiation of several subtypes having unique survival outcomes, particularly for tumours highly responsive or
nonresponsive to hormonal or targeted drug therapies. Currently the prognostic and treatment predictive factors
are mainly based on the primary tumour status, even though the distant metastases are the main reason for
breast cancer related deaths. Thus, there is need for novel approaches with higher specificity and sensitivity in
newly developed targeted therapies.
The aim of this thesis was to understand the changes in breast cancer tumour cells and tissues, by comparing
protein expression levels in different conditions, using mass spectrometry. Attention was specifically on the
analysis of patient samples, with pairs of primary tumours and metastases, in order to try to understand what
happens to allow tumour cells to be able to metastasise and to identify novel molecular markers. Hence we also
investigated the biological functions of proteins by integrating information about the processes and pathways in
which these proteins take part in order to be able to better understand the contribution of different proteins to
breast cancer development. Further we have explored molecular classification markers for breast cancer tumours
into major intrinsic subtypes. Our results demonstrated a great overlap of subtypes, using gene expression and
protein expression profiling. In conclusion, all our findings together show the great need for improved and early
cancer detection and treatment as well as need for development and promises of personalized medicine. (Less)
Please use this url to cite or link to this publication:
author
supervisor
opponent
  • Doktor Vilanueva, Josep, Vall d'Hebron Institute of Oncology, Barcelona, Spain
organization
publishing date
type
Thesis
publication status
published
subject
keywords
Breast cancer, Proteomics
pages
67 pages
publisher
Department of Immunotechnology, Lund University
defense location
Lecture hall Lundmarksalen, Astronomihuset, Sölvegatan 27, Faculty of Engineering, Lund University LTH, Lund
defense date
2017-09-29 09:00
ISBN
978-91-7753-394-8
978-91-7753-393-1
language
English
LU publication?
yes
id
67640596-1332-47c6-bae7-a42d1daa24dd
date added to LUP
2017-09-01 15:03:30
date last changed
2017-09-06 12:30:26
@phdthesis{67640596-1332-47c6-bae7-a42d1daa24dd,
  abstract     = {Breast cancer is one of the most common cancers in women. It is most commonly treated by the surgical removal <br/>of the tumour in combination with (neo)-adjuvant therapy (hormone, chemo- or radio- therapy before or after <br/>surgery). However, a large number of patients are over treated, with approximately 60% being given adjuvant <br/>therapy when already cured by surgery alone. This causes many undesirable side effects and cost hence, there is <br/>great need for new diagnostic and prognostic methods to decide if patients are in need of adjuvant therapy. <br/>A number of prognostic and treatment predictive factors have been established such as tumour size, hormone <br/>receptor status, histological grade and age. Hereditary predisposition to developing cancer can be a factor, with <br/>several high penetrance genes identified such as BRCA1 and BRCA2 genes as well as many as a dozen lower <br/>risk genes that are however additive in effect. Molecular subtyping has significant prognostic value allowing the <br/>differentiation of several subtypes having unique survival outcomes, particularly for tumours highly responsive or <br/>nonresponsive to hormonal or targeted drug therapies. Currently the prognostic and treatment predictive factors <br/>are mainly based on the primary tumour status, even though the distant metastases are the main reason for <br/>breast cancer related deaths. Thus, there is need for novel approaches with higher specificity and sensitivity in <br/>newly developed targeted therapies. <br/>The aim of this thesis was to understand the changes in breast cancer tumour cells and tissues, by comparing <br/>protein expression levels in different conditions, using mass spectrometry. Attention was specifically on the <br/>analysis of patient samples, with pairs of primary tumours and metastases, in order to try to understand what <br/>happens to allow tumour cells to be able to metastasise and to identify novel molecular markers. Hence we also <br/>investigated the biological functions of proteins by integrating information about the processes and pathways in <br/>which these proteins take part in order to be able to better understand the contribution of different proteins to <br/>breast cancer development. Further we have explored molecular classification markers for breast cancer tumours <br/>into major intrinsic subtypes. Our results demonstrated a great overlap of subtypes, using gene expression and <br/>protein expression profiling. In conclusion, all our findings together show the great need for improved and early <br/>cancer detection and treatment as well as need for development and promises of personalized medicine.},
  author       = {Kurbasic, Emila},
  isbn         = {978-91-7753-394-8},
  keyword      = {Breast cancer,Proteomics},
  language     = {eng},
  month        = {09},
  pages        = {67},
  publisher    = {Department of Immunotechnology, Lund University},
  school       = {Lund University},
  title        = {Landscaping the cell surface proteome of breast cancer : Following pathways through organelles to the plasma membrane},
  year         = {2017},
}