Background
Systemic therapy with conventional and targeted drugs is one of the principal modes of treatment of cancer, but the effectiveness of this therapy depends on the presence of respective molecular traits [1] and it is limited by drug resistance [2]. Drug resistance means that the treatment is effective initially in killing the cancer cells, but due to the heterogeneity of the cancer cells of the tumor and their ability to adapt to the treatment, some cancer cells become resistant to the drug given during the treatment [3]. This may result in the re-growth of the tumor although the patient is given the drug. Drug resistance remains one of the biggest challenges in cancer therapy, and it is important to obtain a better understanding of the molecular mechanisms underlying this process [2].
Aims of the project
The objective of this master project is to obtain a better understanding of the role of intercellular communication in drug resistance. One important type of intercellular communication occurs via specialized channels between neighboring cells, called gap junction channels. These channels allow for the direct transfer of ions and small molecules between adjacent cells [4]. Gap junction channels have numerous essential roles in human physiology, including the regulation of cell proliferation and differentiation and the maintenance of tissue homeostasis [4]. A large body of experimental work indicates that loss of intercellular communication via gap junction channels is involved in cancer pathogenesis and that it can contribute to drug resistance [5]. This master project aims to obtain a better understanding of the molecular mechanisms involved in the loss of gap junction channels during cancer pathogenesis, and to study how this loss contributes to resistance to chemotherapeutic drugs used in the clinic to treat cancer.
Methods
Methods that will be used include cell culture, DNA/siRNA transfection, confocal microscopy, co-immunoprecipitation, western blotting, live-cell imaging, assays for measuring cell viability, cell-cell communication assays, and drug sensitivity screens.
Study and research environment
The project will be carried out at The Department of Molecular Oncology, Institute for Cancer Research, Radiumhospitalet, Oslo University Hospital. Our department currently has approximately 40 members. We have a strong emphasis on teaching and supervising students, and there are currently 10 PhD students and three Master’s students in our department. The Master’s student starting on this project will work in close collaboration with other Master's students and PhD students, as well as scientists, in the department. You can read more about our research department on this website: http://www.ous-research.no/molecularoncology/.
References
1. La Thangue NB, Kerr DJ: Predictive biomarkers: a paradigm shift towards personalized cancer medicine. Nat Rev Clin Oncol 2011, 8(10):587-596.
2. Vasan N, Baselga J, Hyman DM: A view on drug resistance in cancer. Nature 2019, 575(7782):299-309.
3. Cancer Drug Resistance: Unraveling Its Complexity; The National Cancer Institute. https://wwwcancergov/research/annual-plan/scientific-topics/drug-resistance.
4. Goodenough DA, Paul DL: Gap junctions. Cold Spring Harb Perspect Biol 2009, 1(1):a002576.
5. Aasen T, Leithe E, Graham SV, Kameritsch P, Mayan MD, Mesnil M, Pogoda K, Tabernero A: Connexins in cancer: bridging the gap to the clinic. Oncogene 2019, 38(23):4429-4451.