Abstract A05: Derivation of chemotherapeutic combination against gastric cancer cells via synthetic lethal targeting of conserved drug-resistance network in fission yeast surrogate

Cancer is a global health problem and there is a critical need for new advancements in its management and treatment if we are to meet the projected increase in new cases. One important challenge facing clinicians is how to determine the most appropriate treatment strategy for patients. Thus far, chemotherapy has remained the mainstay for cancer management. Contemporary chemotherapeutic treatments incorporate the use of typically three to four agents in combination. The determination of the most suitable drug combination profoundly affects chemotherapeutic success. However, selecting the most appropriate drugs for such therapy is not necessarily a straightforward task. Here, we describe a targeted approach that can facilitate the reliable selection of chemotherapeutic drug combinations through the interrogation of drug-resistance gene networks. Our approach employed the single-cell eukaryote fission yeast (Schizosaccharomyces pombe) as a model of proliferating cells using a synthetic lethality workflow. Using a group of genes that we have uncovered to confer responsiveness towards the topoisomerase II inhibitor doxorubicin, a widely applied therapeutic agent in a wide range of cancers. We assessed the genetic overlap of the doxorubicin responsive network with that of several other chemotherapeutic agents harboring varied mechanisms of action. From these effort, we have determined a synergistic combination between three chemotherapeutic agents that include the intrastrand cross...
Source: Molecular Cancer Therapeutics - Category: Cancer & Oncology Authors: Tags: Model Organisms to Identify Synthetic Lethal Interactions: Poster Presentations - Proffered Abstracts Source Type: research