Consequences of cell death in the model organism Drosophila melanogaster: potential implications for cancer treatments

Delano, Angela

Undergraduate Honors Thesis

Consequences of cell death in the model organism Drosophila melanogaster: potential implications for cancer treatments Public Deposited

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Citeable URL: https://scholar.colorado.edu/concern/undergraduate_honors_theses/kk91fm390

Abstract

The fruit fly Drosophila melanogaster shares nearly 75% of known human disease-related genes (Pandey 2011). With its rapid life cycle, simplified genome, and widespread availability, this model organism provides a valuable entry point for cancer research in genetic studies and small-molecule drug screens. In humans, cancer treatments frequently involve the interchange of radiation therapy and chemotherapy in order to avoid overwhelming doses of a single method. Such regimens are administered in intervals to allow a recovery period for a patient’s integral, normal cell types. A recent study in Drosophila tissues found that these healing intermissions allow dying cells to confer enhanced survival to surrounding cells through a form of non-autonomous cell-signaling protection deemed “The Mahakali Effect” (Bilak 2014). Similar survival mechanisms have been identified in human cancer patients (Sun 2012), and the ability of tumors to acquire resistance to radio and chemotherapy contributes to over 90% of treatment failures in metastatic carcinomas (Longley 2005). The Mahakali Effect, named after a Hindu goddess of death who protects her followers, describes the process by which previously killed or damaged cells protect neighboring healthy cells from subsequent radiation damage. The genes Tie and bantam were found to be necessary for this protection (Bilak 2014), and this thesis aims to determine if these genes are employed in the protective mechanism by undead cells. Undead cells are those whose apoptosis (programmed cell death) has been initiated but not completed. This is achieved through the inhibition of executioner and pro-apoptotic caspases (Dischtel-Danjoy 2013). Apoptosis serves the essential function of destroying mutated, precancerous cells, so inhibition of self-destruction makes undead cells more susceptible to tumorigenesis (Don Ryoo 2012). The ultimate goal of this research is to contribute to the ongoing cancer drug development to inhibit the protective effect, so that rounds of cancer treatments involving cytotoxic drug therapy followed by radiation do not lead to progressively more protected and resistant tumor cells (Yu 2012; Bilak 2014). The results of this research suggest that Tie is not required for the protective effect in undead cells, while bantam appears to be important, yet not entirely responsible, for this effect. In this case, bantam has a permissive role rather than an instructive role, and the permissive threshold remains to be determined. Further gene candidate testing will be necessary in order to elucidate both the permissive and instructive components of cell-cell protection in undead Drosophila melanogaster tissues.

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