Designing novel strategies against aggressive solid cancers
Field: Cancers
Location: Translational Research Institute
Type of student:
- Both HDR and Extra-curricular
Type of work:
- Literature review
- Systematic review
- Wet lab work
Brief synopsis:
Human papillomavirus (HPV) is a sexually transmitted virus accountable for ~600,000 cases of cancers of the cervix, oropharyngeal and other genital tissues worldwide, reported annually. Our laboratory focusses on the study of cervical cancer and oropharyngeal cancers because they are highly aggressive and prone to metastasis to different organs in the body. Also, these cancers demonstrate very high recurrence rate (50-70%) within 2 years of completing standard of care systemic therapy (chemotherapy and radiotherapy pre/post-surgery). Given the limitation of current therapies, there is an existing need for the development of novel therapeutic approaches. Oncogenic HPV viral proteins E6 and E7 disturb the homeostasis of HPV infected epithelial cells, promoting cellular transformation by well-defined means. Interestingly, both E6 and E7 have been shown to upregulate/amplify the expression of MYC, a master transcription regulator known to be deregulated in ≥70% of human cancers. MYC plays a central role in driving tumorigenesis and augments resistance against pharmacological therapies. Our rationale is to chemically inhibit the function of MYC oncogene to overcome chemo-resistance. Using a novel drug molecule known to inhibit MYC, we will be challenging HPV-transformed cell lines in vitro, to characterize the functional phenotype of these cells in the presence and absence of chemotherapy.
Outcome: The project aims to understand the importance of MYC oncogene in causing resistance to chemotherapies among HPV-driven malignancies. The study will enable the participating student to gain expertise in performing molecular techniques involving gene cloning, cell survival and killing assays, flow cytometry, immunofluorescence, and immunohistochemistry to generate in vitro data. It will also provide the opportunity to learn use of in vitro techniques to test the efficacy of the combination strategy which will lay the foundation for in vivo studies and potential clinical trials.
Prerequisite skills: Basic lab techniques
