Show/Hide Menu
Hide/Show Apps
Logout
Türkçe
Türkçe
Search
Search
Login
Login
OpenMETU
OpenMETU
About
About
Open Science Policy
Open Science Policy
Open Access Guideline
Open Access Guideline
Postgraduate Thesis Guideline
Postgraduate Thesis Guideline
Communities & Collections
Communities & Collections
Help
Help
Frequently Asked Questions
Frequently Asked Questions
Guides
Guides
Thesis submission
Thesis submission
MS without thesis term project submission
MS without thesis term project submission
Publication submission with DOI
Publication submission with DOI
Publication submission
Publication submission
Supporting Information
Supporting Information
General Information
General Information
Copyright, Embargo and License
Copyright, Embargo and License
Contact us
Contact us
Investigation of the drug resistance in capecitabine resistant hct-116, dabrafenib resistant ht-29, and sn-38 resistant ht-29 cell lines using cellular barcoding technology
Download
RanaCanBaygın_Thesis_.pdf
Date
2022-11-3
Author
Baygın, Rana Can
Metadata
Show full item record
This work is licensed under a
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License
.
Item Usage Stats
163
views
28
downloads
Cite This
Cancer is a complex disease, and understanding its biology holds great importance. Tumor cells exhibit hallmarks of cancer, including aberrantly activated signaling pathways and gain or loss genomic alterations that result in alterations in their differentiation programs, survival, proliferation, and programmed cell death. Developing resistance to therapeutic agents is one of the major problems in cancer therapies. Exploiting drug resistance using the principles of clonal evolution can pave the way to overcoming or controlling drug resistance in cancers. Collateral sensitivity as a second-line therapy strategy positively impacts the treatment of cancer, and it could offer novel therapeutic strategies to overcome or control drug resistance. In this study, it was aimed to monitor the development of drug resistance using cellular barcoding technology to identify second-line therapeutic agents that sensitize initially drug-resistant cell populations. To develop the evolutionaryinformed strategy for drug resistance and to study the effect of second-line therapy in colorectal cancer cell lines, barcoded HCT-116 and HT-29 cell lines were used. The barcode analysis showed that the capecitabine resistance in HCT-116 cells was caused by de novo, dabrafenib resistance in HT-29 cells was caused by de novo, and the SN-38 resistance in HT-29 cells was caused by pre-existing alterations in the population. The cell viability assays of drug-resistant cells indicated that collateral sensitivity exists for other drugs. Thus, the development of drug resistance in colorectal cancer cells was associated with pre-existed or de novo mutations depending on a cell line or a drug in the preferred experimental model system and potentially had a great impact on mediating collateral sensitivity as a second-line therapy option.
Subject Keywords
Colorectal cancer
,
drug resistance
,
collateral sensitivity
,
second-line therapies
URI
https://hdl.handle.net/11511/101129
Collections
Graduate School of Natural and Applied Sciences, Thesis
Suggestions
OpenMETU
Core
Identification of rare cell types in lung cancer and investigation of their use in prognosis
Yıldız, Cemal; Şengül Babal, Simge; Pir, Pınar (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10)
Cancer is a complex, dynamic and heterogeneous disease. Identification of tumor heterogeneity holds a significant promise not only on tumor classification but also on predicting the prognosis and choosing the right treatment. Therefore, it is essential to investigate tumor heterogeneity in a regular diagnosis procedure. Tumors contain variety of cell types such as malignant cells, non-malignant cells, immune cells, and rare cells (i.e., dormant cells (DRM) and cancer stem cells (CSC))....
Identification of gene mutations involved in drug resistance in liver cancer using RNA-SEQ data analysis
Shojaei, Mona; Atalay, Rengül; Acar, Aybar Can; Department of Bioinformatics (2016)
A significant concern in cancer research is the detection of cancer associated somatic mutations. Liver cancer is the 5th most common and 2nd deadliest cancer in the world. Several somatic mutations were previously reported in liver cancer but their relations to chemotherapeutic response was not studied in detail. In this study, the relationship between mutation status and drug treatment response of well-differentiated Huh7 and poorly-differentiated Mahlavu liver cancer cells were analyzed. The RNA-Seq data...
INVESTIGATION OF CLONAL EVOLUTION IN CAPECITABINE RESISTANT CACO-2 AND IRINOTECAN RESISTANT HT-29 CELL LINES BY USING CELLULAR BARCODING TECHNOLOGY
Danışık, Nurseda; Acar, Ahmet; Özen, Can; Department of Biotechnology (2022-10-31)
The development of drug resistance in tumor cells is one of the biggest problems currently in the clinic. As the pace of drug discovery slows and each new drug becomes increasingly expensive to bring to market, it is becoming clearer that better model systems and an understanding of drug resistance mechanisms are needed for second-line therapies. The overall aim of this project is to investigate the clonal evolution and drug resistance in colorectal cancer cell lines Caco-2 and HT-29 by using cellular barco...
Investigation of Effects of Microenvironment and Immune Cells onTumor Growth by Agent Based Modeling
Orta Doğu Teknik Üniversitesi, Deniz Bilimleri Enstitüsü (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10)
Cancer is one of the diseases that humanity suffered for a long time. We understand many aspects of this disease, but there is still much to learn. Because it is a complex disease that affects many processes, organs, cell types, and so on. We need to investigate cellular components, interactions and processes that are related to cancer as a whole to understand its structure. In this scope, investigating the microenvironment of tumors and interactions in it can reveal fundamental features of cancer. One of t...
Detection of rare cell types and patient prognosis in liver cancer
Şengül Babal, Simge; Yıldız, Cemal; Pır, Pınar (Orta Doğu Teknik Üniversitesi Enformatik Enstitüsü; 2022-10)
Cancer is a disease that emerges as a result of complex aberrant processes involving cells that grow and divide uncontrollably and has many patient-specific characteristics. Mutations in genes or changes in the expression of transcripts produce cellular heterogeneity, cancer cells, and tumors, and finally invade other healthy tissues [1]. Primary liver cancer is the second most lethal malignancy worldwide and comprises many molecularly unique subtypes and a highly diverse microenvironment [2]. Among this di...
Citation Formats
IEEE
ACM
APA
CHICAGO
MLA
BibTeX
R. C. Baygın, “Investigation of the drug resistance in capecitabine resistant hct-116, dabrafenib resistant ht-29, and sn-38 resistant ht-29 cell lines using cellular barcoding technology,” M.S. - Master of Science, Middle East Technical University, 2022.