Genomic Research Live

Facilitated by Novogene, the platform will focus on genomics, transcriptomics and other fields of genomic technology, as well as topical research achievements, and research progress from the world’s industry leaders.

Using the wide range of publicity channels at Novogene’s disposal we will provide global coverage for our speakers. We believe that the sharing of expert opinions and ideas will stimulate the scientific research potential of our global research colleagues and promote the sustainable development of life sciences.

We are looking forward to hosting in-depth discussions on the future development of genomic technology to stimulate scientific innovation and promote scientific cooperation.

Coming Lectures

NO.001

Topic: Addressing the new role of cytidine deaminase in pancreatic cancer using transcriptomics

Keywords: pancreatic cancer, DNA replication stress, cytidine deaminase (CDA), DNA targeting drugs

Speaker Introduction

Dr Pierre Cordelier, PhD in Human Physiopathology, is Research Director at INSERM, team leader (therapeutic innovation in pancreatic cancer) and deputy director of the cancer research centre of Toulouse (CRCT). Dr Cordelier research focus is to identify the molecular mechanisms involved into pancreatic tumors oncogenesis and resistance to treatment, to advocate for personalized therapies and help alleviate the dismal prognosis of this disease with no cure.

Lecture Introduction

The objective of this research program is to identify the role of cytidine deaminase, an enzyme otherwise involved in tumor resistance to gemcitabine, is exerting in pancreatic cancer cells.

Abstract

Chronic DNA replication stress and genome instability are two hallmarks of cancer that fuel oncogenesis and tumor diversity. Therapeutic approaches aimed to leverage tumor-specific replication stress to intolerable levels or to expose vulnerabilities for synthetic lethality purpose have recently gained momentum, especially for pancreatic cancer, a disease with no cure. However, the current knowledge is limited considering the molecular mechanisms involved in the replication stress response in pancreatic tumors. Cytidine deaminase (CDA) is involved in the pyrimidine salvage pathway for DNA and RNA synthesis. Loss of CDA induces genomic instability in Bloom Syndrome, and CDA protects tumor cells from chemotherapy with pyrimidine analogs. Here, we show that CDA is overexpressed in genetically instable pancreatic tumors, associates with DNA replication signature and is instrumental for experimental tumor growth. In cancer cells, CDA promotes DNA replication, increases replication fork fitness for controlling replication stress and genomic stability. CDA expression is predictive of DNA-damaging drug efficacy, and targeting CDA relieves resistance to chemotherapy in patients’ models. Our findings shed a new light on the mechanisms by which pancreatic cancer cells control replication stress, and highlight targeting of CDA as a potential therapeutic intervention to defeat tumor resistance to treatment. https://www.biorxiv.org/content/10.1101/2021.10.23.465566v1