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Article ; Online: Soluble immune-checkpoint factors: a potential immunotherapy biomarker.

Tan, Aaron C / Cook, Sarah L / Khasraw, Mustafa

2024 Volume 134, Issue 7

Abstract: There is unmet need for additional biomarkers to better select patients with non-small cell lung cancer (NSCLC) that are likely to benefit from immunotherapy in order to improve patient outcomes, reduce patient toxicity, and relieve the growing burden of ...

Abstract	There is unmet need for additional biomarkers to better select patients with non-small cell lung cancer (NSCLC) that are likely to benefit from immunotherapy in order to improve patient outcomes, reduce patient toxicity, and relieve the growing burden of healthcare costs. In this issue of the JCI, Hayashi and colleagues evaluated soluble forms of the immune checkpoint molecules PD-L1, PD-1, and CTLA-4 in the plasma of patients with advanced NSCLC who had been treated with anti-PD-1/L1 therapy. The findings suggest that these soluble immune-checkpoint factors may provide a complementary biomarker to PD-L1 IHC, although application into the clinic may not be straightforward.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/therapy ; Lung Neoplasms/therapy ; B7-H1 Antigen ; Biomarkers ; Immunologic Factors ; Immunotherapy ; Biomarkers, Tumor
Chemical Substances	B7-H1 Antigen ; Biomarkers ; Immunologic Factors ; Biomarkers, Tumor
Language	English
Publishing date	2024-04-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	3067-3
ISSN	1558-8238 ; 0021-9738
ISSN (online)	1558-8238
ISSN	0021-9738
DOI	10.1172/JCI179352
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Article ; Online: Unraveling the Impact of Intratumoral Heterogeneity on EGFR Tyrosine Kinase Inhibitor Resistance in

Kobayashi, Keigo / Tan, Aaron C

International journal of molecular sciences

2023 Volume 24, Issue 4

Abstract: The advent of tyrosine kinase inhibitors (TKIs) for treating epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) has been a game changer in lung cancer therapy. However, patients often develop resistance to the drugs within ...

Abstract	The advent of tyrosine kinase inhibitors (TKIs) for treating epidermal growth factor receptor (EGFR)-mutated non-small-cell lung cancer (NSCLC) has been a game changer in lung cancer therapy. However, patients often develop resistance to the drugs within a few years. Despite numerous studies that have explored resistance mechanisms, particularly in regards to collateral signal pathway activation, the underlying biology of resistance remains largely unknown. This review focuses on the resistance mechanisms of EGFR-mutated NSCLC from the standpoint of intratumoral heterogeneity, as the biological mechanisms behind resistance are diverse and largely unclear. There exist various subclonal tumor populations in an individual tumor. For lung cancer patients, drug-tolerant persister (DTP) cell populations may have a pivotal role in accelerating the evolution of tumor resistance to treatment through neutral selection. Cancer cells undergo various changes to adapt to the new tumor microenvironment caused by drug exposure. DTP cells may play a crucial role in this adaptation and may be fundamental in mechanisms of resistance. Intratumoral heterogeneity may also be precipitated by DNA gains and losses through chromosomal instability, and the role of extrachromosomal DNA (ecDNA) may play an important role. Significantly, ecDNA can increase oncogene copy number alterations and enhance intratumoral heterogeneity more effectively than chromosomal instability. Additionally, advances in comprehensive genomic profiling have given us insights into various mutations and concurrent genetic alterations other than EGFR mutations, inducing primary resistance in the context of tumor heterogeneity. Understanding the mechanisms of resistance is clinically crucial since these molecular interlayers in cancer-resistance mechanisms may help to devise novel and individualized anticancer therapeutic approaches.
MeSH term(s)	Humans ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Drug Resistance, Neoplasm/genetics ; ErbB Receptors/metabolism ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Mutation ; Tumor Microenvironment ; Tyrosine Kinase Inhibitors/pharmacology
Chemical Substances	EGFR protein, human (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Tyrosine Kinase Inhibitors
Language	English
Publishing date	2023-02-18
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24044126
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Article ; Online: The cost-effectiveness of including liquid biopsy into molecular profiling strategies for newly diagnosed advanced non-squamous non-small cell lung cancer in an Asian population.

Liu, Sibo / Graves, Nicholas / Tan, Aaron C

Lung cancer (Amsterdam, Netherlands)

2024 Volume 191, Page(s) 107794

Abstract: Objectives: Liquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the ... ...

Abstract	Objectives: Liquid biopsy is complementary to tissue biopsy for lung cancer profiling, yet evidence of the cost-effectiveness is limited. This could retard implementation and reimbursement in clinical practice. The aim of this study is to estimate the cost-effectiveness of profiling strategies that include liquid biopsy and to identify the optimal profiling approach for newly diagnosed advanced non-squamous non-small cell lung cancer (NSCLC) in an Asian population using Singapore as an example. Materials and methods: A decision tree and partitioned-survival model was developed from the Singapore healthcare system's perspective to evaluate the cost-effectiveness of five molecular profiling strategies: either tissue or plasma next-generation sequencing (NGS) alone, a concurrent, and two sequential approaches. Model inputs were informed by local data or published literature. Sensitivity analyses and scenario analyses were undertaken to understand the robustness of the conclusions for decision making. The optimal strategy at different willingness-to-pay (WTP) thresholds was presented by cost-effectiveness acceptability frontier and the expected loss curve. Results: The sequential tissue-plasma NGS approach revealed an additional 0.0981 quality adjusted life years (QALYs) for an extra cost of S$3,074 over a 20-year time horizon compared to tissue NGS alone, resulting in an incremental cost-effectiveness ratio (ICER) of S$31,318/QALY and an incremental net monetary benefit of S$1,343 per patient. The findings were sensitive to the costs of pembrolizumab and osimertinib and the probabilities of re-biopsy after tissue NGS. Sequential plasma-tissue NGS and plasma NGS alone were more costly and less effective than alternatives. Conclusion: The sequential tissue-plasma NGS approach generated the highest net monetary benefit and was the optimal testing strategy when WTP was S$45,000/QALY. It retained superiority but understandably with a higher ICER when expensive, non-first line treatments were included. Overall, its routine clinical practice should be proactively considered for newly diagnosed advanced non-squamous NSCLC in an Asian population.
Language	English
Publishing date	2024-04-15
Publishing country	Ireland
Document type	Journal Article
ZDB-ID	632771-0
ISSN	1872-8332 ; 0169-5002
ISSN (online)	1872-8332
ISSN	0169-5002
DOI	10.1016/j.lungcan.2024.107794
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Article ; Online: Targeting the PI3K/Akt/mTOR pathway in non-small cell lung cancer (NSCLC).

Tan, Aaron C

Thoracic cancer

2020 Volume 11, Issue 3, Page(s) 511–518

Abstract: The traditional classification of lung cancer into small cell lung cancer and non-small cell lung cancer (NSCLC) has been transformed with the increased understanding of the molecular alterations and genomic biomarkers that drive the development of lung ... ...

Abstract	The traditional classification of lung cancer into small cell lung cancer and non-small cell lung cancer (NSCLC) has been transformed with the increased understanding of the molecular alterations and genomic biomarkers that drive the development of lung cancer. Increased activation of the phosphatidylinositol 3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway leads to numerous hallmarks of cancer and this pathway represents an attractive target for novel anticancer therapies. In NSCLC, the PI3K/Akt/mTOR pathway has been heavily implicated in both tumorigenesis and the progression of disease. A number of specific inhibitors of PI3K, Akt and mTOR are currently under development and in various stages of preclinical investigation and in early phase clinical trials for NSCLC. Early evidence has yielded disappointing results. Clinical trials, however, have been performed on predominantly molecularly unselected populations, and patient enrichment strategies using high-precision predictive biomarkers in future trials will increase the likelihood of success. A greater understanding of the underlying molecular biology including epigenetic alterations is also crucial to allow for the detection of appropriate biomarkers and guide combination approaches.
MeSH term(s)	Biomarkers, Tumor/metabolism ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/metabolism ; Carcinoma, Non-Small-Cell Lung/pathology ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Molecular Targeted Therapy ; Phosphatidylinositol 3-Kinases/chemistry ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-akt/antagonists & inhibitors ; Signal Transduction ; TOR Serine-Threonine Kinases/antagonists & inhibitors
Chemical Substances	Biomarkers, Tumor ; Protein Kinase Inhibitors ; MTOR protein, human (EC 2.7.1.1) ; TOR Serine-Threonine Kinases (EC 2.7.1.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1)
Language	English
Publishing date	2020-01-27
Publishing country	Singapore
Document type	Journal Article ; Review
ZDB-ID	2625856-0
ISSN	1759-7714 ; 1759-7706
ISSN (online)	1759-7714
ISSN	1759-7706
DOI	10.1111/1759-7714.13328
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Article ; Online: Anti-Angiogenic Therapy in

Tan, Aaron C / Pavlakis, Nick

International journal of molecular sciences

2022 Volume 23, Issue 16

Abstract: The management of advanced lung cancer has been transformed with the identification of targetable oncogenic driver alterations. This includes anaplastic lymphoma kinase ( ...

Abstract	The management of advanced lung cancer has been transformed with the identification of targetable oncogenic driver alterations. This includes anaplastic lymphoma kinase (
MeSH term(s)	Anaplastic Lymphoma Kinase/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; ErbB Receptors/genetics ; Gene Rearrangement ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Protein Kinase Inhibitors/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Protein-Tyrosine Kinases/genetics ; Vascular Endothelial Growth Factor A/genetics
Chemical Substances	Protein Kinase Inhibitors ; Vascular Endothelial Growth Factor A ; Anaplastic Lymphoma Kinase (EC 2.7.10.1) ; ErbB Receptors (EC 2.7.10.1) ; Protein-Tyrosine Kinases (EC 2.7.10.1)
Language	English
Publishing date	2022-08-09
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23168863
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Article ; Online: Response to Swami et al.

Tan, Mimi C / El-Serag, Hashem B / Thrift, Aaron P

The American journal of gastroenterology

2022 Volume 117, Issue 6, Page(s) 1012

Language	English
Publishing date	2022-07-13
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000001740
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Article ; Online: Targeted Therapies for Lung Cancer Patients With Oncogenic Driver Molecular Alterations.

Tan, Aaron C / Tan, Daniel S W

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2022 Volume 40, Issue 6, Page(s) 611–625

Abstract: Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the new ... ...

Abstract	Lung cancer has traditionally been classified by histology. However, a greater understanding of disease biology and the identification of oncogenic driver alterations has dramatically altered the therapeutic landscape. Consequently, the new classification paradigm of non-small-cell lung cancer is further characterized by molecularly defined subsets actionable with targeted therapies and the treatment landscape is becoming increasingly complex. This review encompasses the current standards of care for targeted therapies in lung cancer with driver molecular alterations. Targeted therapies for
MeSH term(s)	Antineoplastic Agents/adverse effects ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Non-Small-Cell Lung/pathology ; Drug Resistance, Neoplasm/genetics ; Gene Rearrangement ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Lung Neoplasms/pathology ; Molecular Diagnostic Techniques ; Molecular Targeted Therapy ; Mutation ; Neoplasm Staging ; Oncogenes ; Phenotype ; Precision Medicine ; Predictive Value of Tests ; Treatment Outcome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor
Language	English
Publishing date	2022-01-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.21.01626
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Article ; Online: Response to Zhu and Xu.

Tan, Mimi C / Thrift, Aaron P

The American journal of gastroenterology

2020 Volume 115, Issue 10, Page(s) 1725

MeSH term(s)	Demography ; Humans ; Life Style ; Metaplasia ; Risk Factors ; Veterans
Language	English
Publishing date	2020-12-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Comment
ZDB-ID	390122-1
ISSN	1572-0241 ; 0002-9270
ISSN (online)	1572-0241
ISSN	0002-9270
DOI	10.14309/ajg.0000000000000721
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Article ; Online: The role of immunotherapy in fusion-driven lung cancer.

Tan, Aaron C / Chan, Johan / Khasraw, Mustafa

Expert review of anticancer therapy

2021 Volume 21, Issue 5, Page(s) 461–464

MeSH term(s)	Carcinoma, Non-Small-Cell Lung/therapy ; Gene Fusion ; Humans ; Immunotherapy ; Lung Neoplasms/therapy
Language	English
Publishing date	2021-03-16
Publishing country	England
Document type	Editorial
ZDB-ID	2112544-2
ISSN	1744-8328 ; 1473-7140
ISSN (online)	1744-8328
ISSN	1473-7140
DOI	10.1080/14737140.2021.1899816
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Article ; Online: Stroke in Asia.

Tan, Kay Sin / Pandian, Jeyaraj Durai / Liu, Liping / Toyoda, Kazunori / Leung, Thomas Wai Hon / Uchiyama, Shinichiro / Kuroda, Sathoshi / Suwanwela, Nijasri C / Aaron, Sanjith / Chang, Hui Meng / Venketasubramanian, Narayanaswamy

Cerebrovascular diseases extra

2024

Abstract: Background There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well- ... ...

Abstract	Background There is a significant burden of stroke in Asia. Asia has the largest population in the world in 2023, estimated at 4.7 billion. Approximately 9.5-10.6 million strokes will be anticipated annually in the backdrop of a diverse group of well-developed and less developed countries with large disparities in stroke care resources. In addition, Asian countries are in varying phases of epidemiological transition. Summary In this review, we examined recent epidemiological features of ischaemic stroke and intracerebral haemorrhage in Asia with recent developments in hyperacute stroke reperfusion therapy and technical improvements in intracerebral haemorrhage. The article also discussed the spectrum of cerebrovascular diseases in Asia which include intracranial atherosclerosis, intracerebral haemorrhage, infective aetiologies of stroke, moyamoya disease, vascular dissection, radiation vasculopathy and cerebral venous thrombosis. Key Messages The review of selected literature and recent updates, call for attention to the different requirements for resources within Asia and highlights the breadth of cerebrovascular diseases still requiring further research and more effective therapies.
Language	English
Publishing date	2024-04-24
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2651613-5
ISSN	1664-5456 ; 1664-5456
ISSN (online)	1664-5456
ISSN	1664-5456
DOI	10.1159/000538928
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