Page 87 - Hospital Authority Convention 2018

Special Sessions

SS2.1 Precision Cancer Management 13:15 Theatre 2

Precision Medicine and an In Vitro Drug Screening – Platform for Treatment of Leukaemia
Leung A
Department of Medicine, The University of Hong Kong, Hong Kong
Acute myeloid leukaemia (AML) is one of the most lethal cancers in Hong Kong, occurring in about 300 patients each HOSPITAL AUTHORITY CONVENTION 2018
year. It is a group of diseases with distinct clinicopathologic, cytogenetic and genetics features, sharing in common an
abnormal increase in blasts in blood and bone marrow. Conventional chemotherapy and allogeneic haematopoietic stem cell
transplantation (HSCT) are the mainstays of treatment. This “one-size fits all” approach for such a heterogeneous disease has
resulted in unsatisfactory treatment outcome and only 30-40% patients can achieve long-term remission. Prognosis of elderly
patients is dismal. There is an unmet clinical need to develop a personalised treatment for AML as guided by biomarkers.
Recent advances in next generation sequencing of leukaemia genome have shed important light on the heterogeneous
and combinatorial driver events and the intricate signaling pathways in this disease. Emerging evidence from in vitro drug
screening has demonstrated its potential value in predicting clinical drug responses in specific AML subtypes. However, the
best culture conditions and readouts have yet to be standardised and the drugs included in these screening exercises have
to be frequently revised in view of the rapid emergence of new therapeutic agents in the oncology field. Recent developments
in microfluidics and single-cell sequencing have further empowered these platforms the ability to examine the intrinsic
heterogeneity in each AML and may be integrated into future clinical trials to develop personalised treatment of AML. Monday, 7 May 2018

SS2.2 Precision Cancer Management 13:15 Theatre 2

Genomic Study on Molecular Pathways of Cancer Development and Its Relevance to Cancer Precision Medicine
Leung SY
Department of Pathology, The University of Hong Kong, Hong Kong

Colorectal cancers (CRC) develop through two major molecular pathways. The majority goes through the adenoma-
carcinoma sequence, with stepwise mutation of APC, KRAS and TP53 genes. A smaller proportion (around 15%) develops
through inactivation of the DNA mismatch repair (MMR) system leading to an accelerated mutation rate and microsatellite
instability (MSI). Some of these molecular alterations are emerging as biomarkers for prognostication, guiding patient
treatment as well as prediction of genetic predisposition for focused preventive screening. CRC with MSI are sensitive to
immune checkpoint inhibition. Furthermore, MSI CRC are more likely to progress through the serrated pathway with RNF43
mutation or R-spondin fusions, thus these patients may be candidate for clinical trials involving WNT upstream inhibitor
treatment. Whilst most late onset CRC with MSI are sporadic due to biallelic inactivation of MLH1 by promoter methylation in
somatic cells, majority of early-onset MSI CRCs are due to hereditary predisposition by way of germline MMR gene mutation
(Lynch Syndrome). Genetic diagnosis to distinguish between germline versus somatic alterations can identify high risk group
for prophylactic screening, and has proven highly effective in cancer prevention. Emerging technologies including next
generation sequencing can facilitate the discovery of novel genes or pathways that contribute to development of inherited or
sporadic gastrointestinal cancers. Finally, emerging organoid culture technology enables direct culture of patients’ cancer
cells for drug sensitivity testing, which coupled with genomic analysis, holds great potential for advancement of cancer
precision medicine through tailored targeted therapy to specific subgroup of patients.

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