New primary liver cancer study calls for n


image: Figure 1: Hepatocellular carcinomas (HCC) diversify during tumor evolution, leading to multiple coexisting subtypes in a significant proportion of HCC that will require combined systemic therapies to treat the disease.
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Credit: Credit: A * STAR’s Genome Institute of Singapore

Singapore, December 13, 2021 – Clinician-researchers and scientists from the National Cancer Center Singapore (NCCS) and the A * STAR’s Genome Institute of Singapore (GIS), in collaboration with the Singapore General Hospital (SGH), the National University Health System, Duke- NUS Medical School, Nanyang Technological University and collaborators from China, Malaysia, Thailand, and the Philippines described a dynamic genomic landscape of tumor heterogeneity in hepatocellular carcinoma (HCC). This research comes from one of the largest prospective cohorts for HCC known as the Precision Medicine in Liver Cancer Study across the Asia-Pacific Network (PLANet). These new findings from PLANet were recently published in the journal National Science Journal (NSR)[1].

Figure 1: Hepatocellular carcinomas (HCC) diversify during tumor progression, leading to multiple coexisting subtypes in a significant proportion of HCC that will require combined systemic therapies to treat the disease.

Credit: A * STAR’s Genome Institute of Singapore

HCC is the seventh most common cancer in the world, but the fourth leading cause of cancer death worldwide due to its high death rate[2]. Surprisingly, a disproportionate 80% of the disease burden is borne by Asian populations. Despite many efforts, there is currently no validated predictive biomarker for systemic therapies in HCC and the efficacy of the treatment remains low. To address this unmet clinical need, a multidisciplinary and multi-institutional collaborative team received funding to establish the flagship Translational and Clinical Research (TCR) program in liver cancer, which is supported by funding from National Research. Singapore Foundation and administered by National Medical Research Council (NMRC) of the Singapore Department of Health[3]. In this program, the PLANet study was initiated to recruit a prospective cohort of HCC patients working with the Asia-Pacific Hepatocellular Carcinoma (AHCC) Trials Group in several Asian countries. Specifically, PLANet aims to understand the molecular diversities within a tumor known as intratumoral heterogeneity (ITH), as well as how we can use this understanding to guide patient stratification and treatment of the tumor. CHC. In 2017, the group discovered that HCC exhibited a wide range of genetic ITHs in patients.[4].

The study and its conclusions

The current study is based on a cohort of 67 patients from four Asian countries of the PLANet study and is the ITH’s first study across multi-omic data layers (genome, transcriptome, immunome) in HCC. The researchers found variations in different regions of the same tumor for genetic (DNA mutation) and transcriptomic (RNA expression) profiles. In particular, they found that the level of these variations differs from patient to patient, and that over 30% of patients have high transcriptomic ITH, where a single tumor may contain multiple transcriptomic subtypes.

Such a dynamic evolutionary process in HCC helps explain the poor response to systemic therapy in HCC, where therapies addressing only one set of molecular targets are not sufficient. Using the PLANet cohort, the authors demonstrated how combination therapies can potentially treat elevated ITH to increase treatment response rates for HCC. The findings of this research provide a new scientific rationale for the development of innovative therapies for HCC. In the next phase, the group will focus on how to improve treatment outcomes for liver cancer by targeting this dynamic changing heterogeneity.

The PLANet study also provided researchers and clinicians with an atlas to assess the evolutionary history of liver cancer. This genomic information will provide a solid foundation for understanding how individual patients might respond differently to drug treatments, thus enabling a precision medicine approach to treat patients differently in the future. Data from this study are now publicly available through the Singapore Oncology Data Portal (OncoSG)[5] which enables integration, visualization, analysis and sharing of cancer genomic datasets generated in Singapore.

Dr Zhai Weiwei, former GIS Principal Investigator who co-led this work, said: “This study described the first comprehensive landscape of tumor heterogeneity in HCC, providing a solid basis for exploiting tumor evolution. for the prognosis and treatment of patients ”.

Study lead author Professor Pierce Chow, PLANet Principal Investigator and Principal Consultant, Department of Hepato-Pancreato-Biliary Surgery / Transplantation, Division of Surgery and Surgical Oncology at SGH and NCCS, said: ” I have been treating HCC for over 20 years and have conducted multinational clinical trials in this cancer, but HCC remains a very difficult malignancy. Significant scientific breakthroughs are needed to further improve patient outcomes and our current findings are an important step in this direction. ”

– TO FINISH –

For media questions and clarification, please contact:

Singapore National Cancer Center

Dharshini Subbiah

Executive Assistant, Corporate Communications

PV: +65 9616 7532

Email: [email protected]

Singapore Genome Institute, A * STAR

Lyn lai

Agent, Corporate Communications Office

Phone. : +65 6808 8258

PV: +65 8755 8759

Email: [email protected]

About the Singapore National Cancer Center (NCCS)

The National Cancer Center Singapore (NCCS) is a leading national and regional tertiary cancer center with specialists who are experts in the treatment of cancer. The NCCS deals with the majority of cancer cases in Singapore’s public health sector. In addition to providing holistic and multidisciplinary oncology care, our clinicians and scientists collaborate with local and international partners to conduct solid and cutting-edge clinical and translational research. To realize the vision of being a global cancer center, the NCCS provides world-class care and shares its vast experience and expertise by training local and international healthcare professionals.

To meet growing needs, the new NCCS building will be completed in 2022 with increased capacity and expanded facilities dedicated to cancer care, rehabilitation, research and education. To give patients the best treatment outcomes, the NCCS will provide access to advanced and innovative treatments such as proton therapy at the new Goh Cheng Liang Proton Therapy Center.

For more information, please visit: www.nccs.com.sg

About the A * STAR Genome Institute of Singapore (GIS)

The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A * STAR). He has a global vision that seeks to use genomic science to achieve extraordinary improvements in human health and public prosperity. Created in 2000 as a genomic discovery center, the GIS pursues the integration of technology, genetics and biology towards an academic, economic and societal impact, with the mission of “reading, revealing and writing DNA for a better Singapore and a better world ”.

The main research areas of the GIS include precision medicine and population genomics, genomic informatics, space and unicellular systems, epigenetic and epitranscriptomic regulation, genome architecture and design, and sequencing platforms. . The GIS genomic infrastructure is also used to train new scientific talent, to serve as a gateway for academic and industrial research and to explore high-impact scientific questions.

For more information on GIS, please visit www.a-star.edu.sg/gis.

About the Agency for Science, Technology and Research (A * STAR)

A * STAR is Singapore’s leading public sector R&D agency. Through open innovation, we collaborate with our partners in the public and private sectors for the benefit of the economy and society. As a science and technology organization, A * STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and improves lives by improving societal outcomes in healthcare, urban living and sustainability. A * STAR plays a key role in nurturing scientific talent and leaders for the broader research community and industry. A * STAR’s R&D activities range from biomedical sciences to physical sciences and engineering, with research entities mainly located in Biopolis and Fusionopolis. For current news, visit www.a-star.edu.sg.

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[1] Zhai, W. et al. Dynamic phenotypic heterogeneity and evolution of several RNA subtypes in hepatocellular carcinoma: the PLANET study. Natl. Sci. Rev. (2021) doi: 10.1093 / nsr / nwab192

[2] Singal, AG, Lampertico, P. & Nahon, P. Epidemiology and surveillance of hepatocellular carcinoma: new trends. J. Hepatol. 72, 250-261 (2020)

[3] SingHealth Clinician Scientists Win National Brain Tumor and Liver Cancer Research Grant. http://www.sgh.com.sg:80/news/awards/singhealth-clinician-scientists-win-national-grant-to-research-brain-tumeurs-liver-cancer

[4] Zhai, W. et al. The spatial organization of intratumoral heterogeneity and the evolutionary trajectories of metastases in hepatocellular carcinoma. Nat. Commmon. 8, 4565 (2017)

[5] OncoSG. https://src.gisapps.org/OncoSG_public/study/summary?id=GIS041




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