Dr. Vilmantė Žitkutė has joined the ranks of PhDs at the Vilnius University Life Sciences Center (VU LSC). After defending her thesis "The Analysis of the Molecular Mechanisms of Resistance to 5-fluorouracil and Oxaliplatin in Human Colorectal Carcinoma Cells", she was awarded a PhD in biochemistry. Congratulations!
The academic consultant of this dissertation is VU LSC researcher Dr. Aušra Sasnauskienė.
The Dissertation Defence Panel is composed of Chairwoman Prof. Daiva Baltriukienė (VU LSC), Dr. Veronika Viktorija Borutinskaitė (VU LSC), Dr. Lina Prasmickaitė (Oslo University Hospital, Norway), Prof. Dr. Kęstutis Sužiedėlis (National Cancer Institute), Dr. Giedrius Vilkaitis (VU LSC).
Introduction:
Colorectal cancer (CRC) ranks third in incidence and second in deaths from cancer. One of the reasons for this high mortality is late diagnosis. The most common treatment for advanced CRC is chemotherapy with 5-fluorouracil (5-FU) or its combination with oxaliplatin (OxaPt) and leucovorin (folinic acid). Another reason - resistance to chemotherapy drugs. 5-FU and OxaPt act by different mechanisms and therefore have different mechanisms of resistance. Main mechanisms of resistance include intracellular drug concentration reduction, DNA damage repair system and survival signaling pathways activation, programmed cell death inhibition, drug neutralization or changes in the targets. Understanding the molecular mechanisms of resistance to chemotherapeutic drugs remains an important area of research to identify precise targets and discover drugs that improve cancer treatment outcomes.
Inflammatory processes play an important role in the development of CRC and may also play a role in the development of resistance. One of the most recently discovered mechanisms of resistance to chemotherapeutic drugs is the changes in the tumor cell secretome (TCS), i.e., a set of molecules secreted by cancer cells that promote the development of cancer. Chemotherapeutic drugs can alter TCS and thus promote resistance. Cytokines, small signaling molecules that regulate important processes for cancer progression, are part of the TCS, but little is known about their impact on chemoresistance to chemotherapy.
Serpins, serine protease inhibitors, also make an impact for CRC progression, they regulate angiogenesis, inflammation, extracellular matrix remodeling, programmed cell death and cell development, and changes in their expression are associated with tumor progression. Autophagy in cancer cells can play a dual role in inhibiting their development or, conversely, preventing unfavorable conditions. CRC tissues show increased levels of the selective autophagy receptor p62 compared to healthy tissues, and this protein is associated with cancer cell aggressiveness and poor prognosis of patients with cancer. Although there is growing evidence of changes in p62 levels in resistant cells and effects on resistance but the exact mechanism underlying resistance is still not clear.