QNRF-funded Research helps provide better cancer treatment in Qatar
As far as cancer genetic studies are concerned, the Arab/Qatari ethnic populations have not been extensively studied which has led to disparate gaps in our knowledge of cancer predisposition genes in these populations. Among the different types of primary breast cancers, triple-negative breast cancer (TNBC) remains the most important challenge and there is a significant gap in our understanding of the genetic, and environmental factors underlying its etiology and progression.
To address this gap, researchers from Weill Cornell Medicine - Qatar (WCM-Q), led by Dr. Latif Chouchane are conducting an extensive research study titled, “Exploring Drug Resistance Mechanisms in Triple Negative Breast Cancers: From Patient Derived Organoids towards Precision Medicine,” (PPM 04-0311-200035) supported jointly by Qatar National Research Fund and Qatar Genome Programme under their Path towards Precision Medicine program. Based on the findings of this project, a clinical pilot project has been launched at Hamad Medical Corporation aiming to provide oncogenetics services to the individuals identified at an increased risk for hereditary breast/ovarian cancers and to their families in Qatar.
According to Dr. Chouchane, their project is aimed at systematically defining the genomic alteration that drives TNBC and identifying drug targets as there is an unmet need to unveil the characteristics of TNBC in the Arab populations. Breast cancers related to a BRCA mutation are also more likely to be triple-negative breast cancer (TNBC), which can be more aggressive and difficult to treat. Therefore, among the goals of the project is to get insight into the spectrum of pathologic variants of BRCA1 and investigate whether the Qatari population carries any specific pathogenic variants in BRCA1/2 such as ethnicity-based BRCA mutation.
By addressing this unmet challenge, this research project has excellent potential to advance awareness in the field. Moreover, the outcomes of this project can also help develop targeted therapeutics, which are urgently needed for TNBC because the tumors are exceptionally resistant to chemotherapy.
Therefore, the project being carried out by Dr. Chouchane and his team is very important as it addresses the need for enhanced and personalized TNBC models, and its outcomes can be implemented as several essential features of TNBC have already been shown to be replicated by patient-derived organoids (PDOs). Hence, the PDOs being developed here in Qatar at WCM-Q will provide greater flexibility to establish a regional resource that models the TNBC of Arab women.
Technically, the project will take advantage of recent high throughput techniques such as whole-genome sequencing to extend the identification of variants or mutations present in the non-coding regions of the genome. In addition, the research team will be using RNA-sequencing to identify the transcripts and pathways that are altered in the TNBC of Arab women.
The research outcomes of this project will greatly benefit Arab societies by helping to better understand their specific risk and risk factors associated with TNBCs. Moreover, they will help identify any novel somatic mutations or their frequency present in Arab TNBC patients that may be distinct from the other ethnic groups. The successful completion of this project would also advance our understanding of the primary and secondary driver gene mutations in TNBCs in women of Arab descent and the ethnic-based BRCA standard for the Qatari population.
This could lead to the establishment of the Arab-specific patient-derived organoid bank here in Qatar which will be an excellent resource for modeling disease progression in Arab populations. Furthermore, the PDOs will provide therapeutic options in drug selection and impact outcomes not only for TNBC patients but also other patients with cancers refractory to other forms of treatment in the long run. This understanding will immensely help improve the prognosis and survival of TNBC patients in Qatar and the wider region.
As part of this effort, and through the support and collaboration with Qatar Genome Programme, some findings have been recently published in the high-impact journal, “The Lancet Oncology” as a full original research article titled, "Genetic predisposition to cancer across people of different ancestries in Qatar: a population-based cohort study." Appreciating the role of QNRF’s support, Dr. Chouchane says, “We are grateful to QNRF as their funding not only contributed to generating an exceptional publication but also led to a national collaborative consortium on the subject which brings together researchers from WCM-Q along with other scientists from QF’s Hamad Bin Khalifa University (HBKU), the Qatar Computing Research Institute (QCRI), Sidra Medicine and the Qatar Genome Research Consortium.”