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1. Real-world outcomes of pemetrexed-platinum chemotherapy plus osimertinib after progression on first-line osimertinib in advanced EGFR-mutated NSCLC

Author

Saw, Stephanie P.L., Low, Yi Fen, Lai, Gillianne G.Y., Chan, Landon L., Wong, Wesley K.Y., Tsui, Giselle, Chen, Olivia H., Seet, Amanda O.L., Tan, Wei Chong, Tan, Aaron C., Chan, Johan W.K., Teh, Yi Lin, Tan, Wan-Ling, Ng, Quan Sing, Ang, Mei-Kim, Kanesvaran, Ravindran, Lim, Darren W.T., Tan, Daniel S.W., Mok, Tony S.K., and Li, Molly S.C.

Published
2024
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2. Clinical efficacy and biomarker analysis of dual PD-1/CTLA-4 blockade in recurrent/metastatic EBV-associated nasopharyngeal carcinoma

Author

Lim, Darren Wan-Teck, Kao, Hsiang-Fong, Suteja, Lisda, Li, Constance H., Quah, Hong Sheng, Tan, Daniel Shao-Weng, Tan, Sze-Huey, Tan, Eng-Huat, Tan, Wan-Ling, Lee, Justina Nadia, Wee, Felicia Yu-Ting, Jain, Amit, Goh, Boon-Cher, Chua, Melvin L. K., Liao, Bin-Chi, Ng, Quan Sing, Hong, Ruey-Long, Ang, Mei-Kim, Yeong, Joe Poh-Sheng, and Iyer, N. Gopalakrishna

Published
2023
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5. PD-L1 score as a prognostic biomarker in asian early-stage epidermal growth factor receptor-mutated lung cancer

Author

Saw, Stephanie P.L., Ng, Win Pin, Zhou, Siqin, Lai, Gillianne G.Y., Tan, Aaron C., Ang, Mei-Kim, Lim, Wan-Teck, Kanesvaran, Ravindran, Ng, Quan Sing, Jain, Amit, Tan, Wan Ling, Rajasekaran, Tanujaa, Chan, Johan W.K., Teh, Yi Lin, Pang, Mengyuan, Yeo, Jia-Chi, Takano, Angela, Ong, Boon-Hean, Tan, Eng-Huat, Tan, Sze Huey, Skanderup, Anders J., and Tan, Daniel S.W.

Published
2023
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7. A Randomized Phase 2 Trial of Nivolumab Versus Nivolumab-Ipilimumab Combination in EGFR-Mutant NSCLC

Author

Lai, Gillianne G.Y., Yeo, Jia Chi, Jain, Amit, Zhou, Siqin, Pang, Mengyuan, Alvarez, Jacob J.S., Sim, Ngak Leng, Tan, Aaron C., Suteja, Lisda, Lim, Tze Wei, Guo, Yu Amanda, Shen, Meixin, Saw, Stephanie P.L., Rohatgi, Neha, Yeong, Joe P.S., Takano, Angela, Lim, Kiat Hon, Gogna, Apoorva, Too, Chow Wei, Da Zhuang, Kun, Tan, Wan Ling, Kanesvaran, Ravindran, Ng, Quan Sing, Ang, Mei Kim, Rajasekaran, Tanujaa, Wang, Lanying, Toh, Chee Keong, Lim, Wan-Teck, Tam, Wai Leong, Tan, Sze Huey, Skanderup, Anders M.J., Tan, Eng-Huat, and Tan, Daniel S.W.

Published
2022
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8. Detection of circulating tumor DNA with ultradeep sequencing of plasma cell‐free DNA for monitoring minimal residual disease and early detection of recurrence in early‐stage lung cancer

Author

Tan, Aaron C., primary, Lai, Gillianne G. Y., additional, Saw, Stephanie P. L., additional, Chua, Kevin L. M., additional, Takano, Angela, additional, Ong, Boon‐Hean, additional, Koh, Tina P. T., additional, Jain, Amit, additional, Tan, Wan Ling, additional, Ng, Quan Sing, additional, Kanesvaran, Ravindran, additional, Rajasekaran, Tanujaa, additional, Kalashnikova, Ekaterina, additional, Renner, Derrick, additional, Sudhaman, Sumedha, additional, Malhotra, Meenakshi, additional, Sethi, Himanshu, additional, Liu, Minetta C., additional, Aleshin, Alexey, additional, Lim, Wan‐Teck, additional, Tan, Eng‐Huat, additional, Skanderup, Anders J., additional, Ang, Mei‐Kim, additional, and Tan, Daniel S. W., additional

Published
2024
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9. Pairing a prognostic target with potential therapeutic strategy for head and neck cancer

Author

Lek, Sze Min, Li, Ke, Tan, Qiu Xuan, Shannon, Nicholas B., Ng, Wai Har, Hendrikson, Josephine, Tan, Joey W.S., Lim, Hui Jun, Chen, Yudong, Koh, Kelvin K.N., Skanthakumar, Thakshayeni, Kwang, Xue Lin, Chong, Fui Teen, Leong, Hui Sun, Tay, Gerald, Putri, Natascha Ekawati, Lim, Tony Kiat Hon, Hwang, Jacqueline S.G., Ang, Mei Kim, Tan, Daniel S.W., Tan, Ngian Chye, Tan, Hiang Khoon, Kon, Oi Lian, Soo, Khee Chee, Iyer, N. Gopalakrishna, and Ong, Chin-Ann J.

Published
2020
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10. High-Dimensional Characterization of the Systemic Immune Landscape Informs on Synergism Between Radiation Therapy and Immune Checkpoint Blockade

Author

Chua, Kevin L.M., Fehlings, Michael, Yeo, Eugenia L.L., Nardin, Alessandra, Sumatoh, Hermi, Chu, Pek Lim, Nei, Wen-long, Ong, Enya H.W., Woo, Wai Yee, Low, Kar Perng, Wang, Haitao, Poon, Dennis J.J., Liang, Zhong-guo, Yao, Kai, Huang, Luo, Toh, Chee Keong, Ang, Mei-Kim, Farid, Mohamad, Cheng, Xin Min, Kanesvaran, Ravindran, Dent, Rebecca, Wee, Joseph T.S., Lim, Tony K.H., Iyer, N. Gopalakrishna, Tan, Daniel S.W., Soo, Khee Chee, Newell, Evan W., and Chua, Melvin L.K.

Published
2020
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11. Combinatorial hypofractionated radiotherapy and pembrolizumab in anaplastic thyroid cancer

Author

Tan, Janice Ser Huey, primary, Tay, Timothy Kwang Yong, additional, Ong, Enya Hui Wen, additional, Fehlings, Michael, additional, Tan, Daniel Shao-Weng, additional, Sukma, Nadiah Binte, additional, Chen, Eileen Xueqin, additional, Sng, Jen-Hwei, additional, Yip, Connie Siew Poh, additional, Lim, Kok Hing, additional, Lim, Darren Wan-Teck, additional, Iyer, Narayanan Gopalakrishna, additional, Hwang, Jacqueline Siok Gek, additional, Chua, Melvin Lee Kiang, additional, and Ang, Mei-Kim, additional

Published
2024
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12. Clinical and Genomic Features of HER2 Exon 20 Insertion Mutations and Characterization of HER2 Expression by Immunohistochemistry in East Asian Non–Small-Cell Lung Cancer

Author

Tan, Aaron C., Saw, Stephanie P.L., Chen, Jianbin, Lai, Gillianne G.Y., Oo, Hlaing Nwe, Takano, Angela, Lau, Dawn P.X., Yeong, Joe P.S., Tan, Gek San, Lim, Kiat Hon, Skanderup, Anders J., Chan, Johan W.K., Teh, Yi Lin, Rajasekaran, Tanujaa, Jain, Amit, Tan, Wan Ling, Ng, Quan Sing, Kanesvaran, Ravindran, Lim, Wan-Teck, Ang, Mei-Kim, and Tan, Daniel S.W.

Published
2022
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14. Identifying correlates of post treatment responses for unresectable locally advanced non-small cell lung cancer (LA NSCLC).

Author

Chua, Kevin Lee Min, primary, Lai, Gillianne, additional, Tan, Aaron C., additional, Saw, Stephanie Pei Li, additional, Tan, Wan Ling, additional, Jain, Amit, additional, Chia, Brendan Seng Hup, additional, Li, Youquan, additional, Fong, Kam-Weng, additional, Siow, Siow Tian, additional, Ng, Quan Sing, additional, Thiagarajan, Anuradha, additional, Kanesvaran, Ravindran, additional, Ng, Wee Loon, additional, Lim, Darren Wan-Teck, additional, Yip, Connie Siew Poh, additional, Skanderup, Anders, additional, Tan, Sze Huey, additional, Ang, Mei-Kim, additional, and Tan, Daniel Shao-Weng, additional

Published
2023
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15. Association of Claudin-1 overexpression with immune exclusion in nasopharyngeal carcinoma and its potential as a novel therapeutic target.

Author

Yeo, Eugenia Li Ling, primary, Ong, Enya, additional, Neo, Jialing, additional, Chow, Wen Min, additional, Tan, Kah Min, additional, Tan, Janice Ser Huey, additional, Yeong, Joe Poh Sheng, additional, Lim, Tony Kiat Hon, additional, Hwang, Jacqueline Siok Gek, additional, Ng, Quan Sing, additional, Soong, Yoke Lim, additional, Ang, Mei-Kim, additional, Tan, Sze Huey, additional, Chua, Melvin Lee Kiang, additional, and Lim, Darren Wan-Teck, additional

Published
2023
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17. Individualized Molecular Profiling for Allocation to Clinical Trials Singapore Study—An Asian Tertiary Cancer Center Experience

Author

Seet, Amanda O. L., Tan, Aaron C., Tan, Tira J., Ng, Matthew C. H., Tai, David W. M., Lam, Justina Y. C., Tan, Gek San, Gogna, Apoorva, Too, Chow Wei, Tan, Bien Soo, Takano, Angela, Lim, Alvin, Lim, Tse Hui, Lim, Soon Thye, Dent, Rebecca Alexandra, Ang, Mei Kim, Yap, Yoon-Sim, Tan, Iain B. H., Choo, Su Pin, Toh, Chee Keong, Lim, Elaine H., Farid, Mohamad, Skanderup, Anders Jacobsen, Iyer, N. Gopalakrishna, Lim, Wan Teck, Tan, Eng Huat, Lim, Tony K. H., and Tan, Daniel S. W.

Published
2021
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18. Dearth of smoking-induced mutations in NSRO-driven non-small-cell lung cancer despite smoking exposure

Author

Huang, Chen-Yang, primary, Jiang, Nanhai, additional, Shen, Meixin, additional, Lai, Gillianne, additional, Tan, Aaron C., additional, Jain, Amit, additional, Saw, Stephanie P., additional, Ang, Mei-Kim, additional, Ng, Quan Sing, additional, Lim, Darren Wan-Teck, additional, Kanesvaran, Ravindran, additional, Tan, Eng-Huat, additional, Tan, Wan Ling, additional, Ong, Boon-Hean, additional, Chua, Kevin L., additional, Anantham, Devanand, additional, Takano, Angela, additional, Lim, Tony K.H., additional, Tam, Wai Leong, additional, Sim, Ngak Leng, additional, Skanderup, Anders J., additional, Tan, Daniel S.W., additional, and Rozen, Steven G., additional

Published
2023
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22. Supplementary Data from Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities

Author

Chua, Khi Pin, primary, Teng, Yvonne H.F., primary, Tan, Aaron C., primary, Takano, Angela, primary, Alvarez, Jacob J.S., primary, Nahar, Rahul, primary, Rohatgi, Neha, primary, Lai, Gillianne G.Y., primary, Aung, Zaw Win, primary, Yeong, Joe P.S., primary, Lim, Kiat Hon, primary, Naeini, Marjan Mojtabavi, primary, Kassam, Irfahan, primary, Jain, Amit, primary, Tan, Wan Ling, primary, Gogna, Apoorva, primary, Too, Chow Wei, primary, Kanesvaran, Ravindran, primary, Ng, Quan Sing, primary, Ang, Mei Kim, primary, Rajasekaran, Tanujaa, primary, Anantham, Devanand, primary, Phua, Ghee Chee, primary, Tan, Bien Soo, primary, Lee, Yin Yeng, primary, Wang, Lanying, primary, Teo, Audrey S.M., primary, Khng, Alexis Jiaying, primary, Lim, Ming Jie, primary, Suteja, Lisda, primary, Toh, Chee Keong, primary, Lim, Wan-Teck, primary, Iyer, N. Gopalakrishna, primary, Tam, Wai Leong, primary, Tan, Eng-Huat, primary, Zhai, Weiwei, primary, Hillmer, Axel M., primary, Skanderup, Anders J., primary, and Tan, Daniel S.W., primary

Published
2023
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23. Supplementary Figure 1 from High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

Author

Ang, Mei-Kim, primary, Patel, Mihir R., primary, Yin, Xiao-Ying, primary, Sundaram, Sneha, primary, Fritchie, Karen, primary, Zhao, Ni, primary, Liu, Yufeng, primary, Freemerman, Alex J., primary, Wilkerson, Matthew D., primary, Walter, Vonn, primary, Weissler, Mark C., primary, Shockley, William W., primary, Couch, Marion E., primary, Zanation, Adam M., primary, Hackman, Trevor, primary, Chera, Bhishamjit S., primary, Harris, Stephen L., primary, Miller, C. Ryan, primary, Thorne, Leigh B., primary, Hayward, Michele C., primary, Funkhouser, William K., primary, Olshan, Andrew F., primary, Shores, Carol G., primary, Makowski, Liza, primary, and Hayes, D. Neil, primary

Published
2023
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24. Data from High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

Author

Ang, Mei-Kim, primary, Patel, Mihir R., primary, Yin, Xiao-Ying, primary, Sundaram, Sneha, primary, Fritchie, Karen, primary, Zhao, Ni, primary, Liu, Yufeng, primary, Freemerman, Alex J., primary, Wilkerson, Matthew D., primary, Walter, Vonn, primary, Weissler, Mark C., primary, Shockley, William W., primary, Couch, Marion E., primary, Zanation, Adam M., primary, Hackman, Trevor, primary, Chera, Bhishamjit S., primary, Harris, Stephen L., primary, Miller, C. Ryan, primary, Thorne, Leigh B., primary, Hayward, Michele C., primary, Funkhouser, William K., primary, Olshan, Andrew F., primary, Shores, Carol G., primary, Makowski, Liza, primary, and Hayes, D. Neil, primary

Published
2023
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25. Supplementary Figure Legend from High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

Author

Ang, Mei-Kim, primary, Patel, Mihir R., primary, Yin, Xiao-Ying, primary, Sundaram, Sneha, primary, Fritchie, Karen, primary, Zhao, Ni, primary, Liu, Yufeng, primary, Freemerman, Alex J., primary, Wilkerson, Matthew D., primary, Walter, Vonn, primary, Weissler, Mark C., primary, Shockley, William W., primary, Couch, Marion E., primary, Zanation, Adam M., primary, Hackman, Trevor, primary, Chera, Bhishamjit S., primary, Harris, Stephen L., primary, Miller, C. Ryan, primary, Thorne, Leigh B., primary, Hayward, Michele C., primary, Funkhouser, William K., primary, Olshan, Andrew F., primary, Shores, Carol G., primary, Makowski, Liza, primary, and Hayes, D. Neil, primary

Published
2023
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26. Supplementary Table 1 from High XRCC1 Protein Expression Is Associated with Poorer Survival in Patients with Head and Neck Squamous Cell Carcinoma

Author

Ang, Mei-Kim, primary, Patel, Mihir R., primary, Yin, Xiao-Ying, primary, Sundaram, Sneha, primary, Fritchie, Karen, primary, Zhao, Ni, primary, Liu, Yufeng, primary, Freemerman, Alex J., primary, Wilkerson, Matthew D., primary, Walter, Vonn, primary, Weissler, Mark C., primary, Shockley, William W., primary, Couch, Marion E., primary, Zanation, Adam M., primary, Hackman, Trevor, primary, Chera, Bhishamjit S., primary, Harris, Stephen L., primary, Miller, C. Ryan, primary, Thorne, Leigh B., primary, Hayward, Michele C., primary, Funkhouser, William K., primary, Olshan, Andrew F., primary, Shores, Carol G., primary, Makowski, Liza, primary, and Hayes, D. Neil, primary

Published
2023
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28. Real world efficacy of osimertinib in second line/beyond in patients with metastatic EGFR+ non-small cell lung cancer and role of paired tumour-plasma T790M testing at tyrosine kinase inhibitor resistance

Author

Ma, Jun, primary, Tan, Sze Huey, additional, Yin, Daniel Xing Cheng, additional, Tran, Nguyen Tuan Anh, additional, Tan, Gek San, additional, Lai, Gillianne Geet Yi, additional, Ang, Mei-Kim, additional, Kanesvaran, Ravindran, additional, Jain, Amit, additional, Rajasekaran, Tanujaa, additional, Tan, Eng-Huat, additional, Lim, Tony Kiat Hon, additional, Tan, Daniel Shao-Weng, additional, Lim, Darren Wan-Teck, additional, Ng, Quan Sing, additional, and Tan, Wan Ling, additional

Published
2023
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30. Long noncoding RNA EGFR-AS1 mediates epidermal growth factor receptor addiction and modulates treatment response in squamous cell carcinoma

Author

Tan, Daniel S W, Chong, Fui Teen, Leong, Hui Sun, Toh, Shen Yon, Lau, Dawn P, Kwang, Xue Lin, Zhang, Xiaoqian, Sundaram, Gopinath M, Tan, Gek San, Chang, Mei Mei, Chua, Boon Tin, Lim, Wan Teck, Tan, Eng Huat, Ang, Mei Kim, Lim, Tony K H, Sampath, Prabha, Chowbay, Balram, Skanderup, Anders J, DasGupta, Ramanuj, and Iyer, N Gopalakrishna

Subjects
Gene expression -- Health aspects, Squamous cell carcinoma -- Genetic aspects -- Development and progression -- Care and treatment, Biological sciences, Health
Abstract

Targeting EGFR is a validated approach in the treatment of squamous-cell cancers (SCCs), although there are no established biomarkers for predicting response. We have identified a synonymous mutation in EGFR, c.2361G [greater than] A (encoding p.Gln787Gln), in two patients with head and neck SCC (HNSCC) who were exceptional responders to gefitinib, and we showed in patient-derived cultures that the A/A genotype was associated with greater sensitivity to tyrosine kinase inhibitors (TKIs) as compared to the G/A and G/G genotypes. Remarkably, single-copy G [greater than] A nucleotide editing in isogenic models conferred a 70-fold increase in sensitivity due to decreased stability of the EGFR-AS1 long noncoding RNA (lncRNA). In the appropriate context, sensitivity could be recapitulated through EGFR-AS1 knockdown in vitro and in vivo, whereas overexpression was sufficient to induce resistance to TKIs. Reduced EGFR-AS1 levels shifted splicing toward EGFR isoform D, leading to ligand-mediated pathway activation. In co-clinical trials involving patients and patient-derived xenograft (PDX) models, tumor shrinkage was most pronounced in the context of the A/A genotype for EGFR-Q787Q, low expression of EGFR-AS1 and high expression of EGFR isoform D. Our study reveals how a 'silent' mutation influences the levels of a lncRNA, resulting in noncanonical EGFR addiction, and delineates a new predictive biomarker suite for response to EGFR TKIs., Author(s): Daniel S W Tan (corresponding author) [1, 2, 3]; Fui Teen Chong [1]; Hui Sun Leong [1]; Shen Yon Toh [1]; Dawn P Lau [1]; Xue Lin Kwang [1]; [...]

Published
2017
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32. Abstract 5114: Ultra-sensitive detection of minimal residual disease (MRD) through whole genome sequencing (WGS) using an AI-based error suppression model in resected early-stage non-small cell lung cancer (NSCLC)

Author

Tan, Aaron C., primary, Saw, Stephanie P., additional, Lai, Gillianne G., additional, Chua, Kevin L., additional, Takano, Angela, additional, Ong, Boon-Hean, additional, Koh, Tina P., additional, Jain, Amit, additional, Tan, Wan Ling, additional, Ng, Quan Sing, additional, Kanesvaran, Ravindran, additional, Rajasekaran, Tanujaa, additional, Deochand, Sunil, additional, Maloney, Dillon, additional, Afterman, Danielle, additional, Lauterman, Tomer, additional, Friedman, Noah, additional, Bourzgui, Imane, additional, Ramaraj, Nidhi, additional, Donenhirsh, Zohar, additional, Veksler, Ronel, additional, Rosenfeld, Jonathan, additional, Kandasamy, Ravi, additional, Tavassoly, Iman, additional, Oklander, Boris, additional, Zviran, Asaf, additional, Lim, Wan-Teck, additional, Tan, Eng-Huat, additional, Skanderup, Anders J., additional, Ang, Mei-Kim, additional, and Tan, Daniel S., additional

Published
2022
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33. PD-L1 score as a prognostic biomarker in Asian patients with early-stage, EGFR-mutated lung cancer.

Author

Saw, Stephanie, primary, Lai, Gillianne, additional, Tan, Aaron C., additional, Zhou, Siqin, additional, Ang, Mei-Kim, additional, Lim, Wan-Teck, additional, Kanesvaran, Ravindran, additional, Tan, Wan Ling, additional, Rajasekaran, Tanujaa, additional, Chan, Johan, additional, Teh, Yi Lin, additional, Ong, Boon-Hean, additional, Takano, Angela M., additional, Tan, Eng Huat, additional, Tan, Sze Huey, additional, and Tan, Daniel Shao-Weng, additional

Published
2022
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35. PD-L1 Score as a Prognostic Biomarker in Asian Early-Stage EGFR-Mutated Lung Cancer

Author

Saw, Stephanie Pei Li, primary, Ng, Win Pin, additional, Zhou, Siqin, additional, Lai, Gillianne, additional, Tan, Aaron, additional, Ang, Mei-Kim, additional, Lim, Wan-Teck, additional, Kanesvaran, Ravindran, additional, Ng, Quan Sing, additional, Jain, Amit, additional, Tan, Wan Ling, additional, Rajasekaran, Tanujaa, additional, Chan, Johan, additional, Teh, Yi Lin, additional, Pang, Mengyuan, additional, Yeo, Jia Chi, additional, Takano, Angela, additional, Ong, Boon-Hean, additional, Tan, Eng Huat, additional, Tan, Sze Huey, additional, Skanderup, Anders, additional, and Tan, Daniel S. W., additional

Published
2022
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36. Association of Clinicopathologic and Molecular Tumor Features With Recurrence in Resected Early-Stage Epidermal Growth Factor Receptor–Positive Non–Small Cell Lung Cancer

Author

Saw, Stephanie P. L., primary, Zhou, Siqin, additional, Chen, Jianbin, additional, Lai, Gillianne, additional, Ang, Mei-Kim, additional, Chua, Kevin, additional, Kanesvaran, Ravindran, additional, Ng, Quan Sing, additional, Jain, Amit, additional, Tan, Wan Ling, additional, Rajasekaran, Tanujaa, additional, Lim, Darren W. T., additional, Tan, Aaron, additional, Fong, Kam Weng, additional, Takano, Angela, additional, Cheng, Xin Ming, additional, Lim, Kiat Hon, additional, Koh, Tina, additional, Ong, Boon-Hean, additional, Tan, Eng Huat, additional, Toh, Chee Keong, additional, Skanderup, Anders J., additional, Tan, Sze Huey, additional, and Tan, Daniel S. W., additional

Published
2021
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39. Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer

Author

Kong, Say Li, primary, Liu, Xingliang, additional, Tan, Swee Jin, additional, Tai, Joyce A., additional, Phua, Ler Yee, additional, Poh, Huay Mei, additional, Yeo, Trifanny, additional, Chua, Yong Wei, additional, Haw, Yu Xuan, additional, Ling, Wen Huan, additional, Ng, Raymond Chee Hui, additional, Tan, Tira J., additional, Loh, Kiley Wei Jen, additional, Tan, Daniel Shao-Weng, additional, Ng, Quan Sing, additional, Ang, Mei Kim, additional, Toh, Chee Keong, additional, Lee, Yi Fang, additional, Lim, Chwee Teck, additional, Lim, Tony Kiat Hon, additional, Hillmer, Axel M., additional, Yap, Yoon Sim, additional, and Lim, Wan-Teck, additional

Published
2021
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40. Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities

Author

Chua, Khi Pin, primary, Teng, Yvonne H.F., additional, Tan, Aaron C., additional, Takano, Angela, additional, Alvarez, Jacob J.S., additional, Nahar, Rahul, additional, Rohatgi, Neha, additional, Lai, Gillianne G.Y., additional, Aung, Zaw Win, additional, Yeong, Joe P.S., additional, Lim, Kiat Hon, additional, Naeini, Marjan Mojtabavi, additional, Kassam, Irfahan, additional, Jain, Amit, additional, Tan, Wan Ling, additional, Gogna, Apoorva, additional, Too, Chow Wei, additional, Kanesvaran, Ravindran, additional, Ng, Quan Sing, additional, Ang, Mei Kim, additional, Rajasekaran, Tanujaa, additional, Anantham, Devanand, additional, Phua, Ghee Chee, additional, Tan, Bien Soo, additional, Lee, Yin Yeng, additional, Wang, Lanying, additional, Teo, Audrey S.M., additional, Khng, Alexis Jiaying, additional, Lim, Ming Jie, additional, Suteja, Lisda, additional, Toh, Chee Keong, additional, Lim, Wan-Teck, additional, Iyer, N. Gopalakrishna, additional, Tam, Wai Leong, additional, Tan, Eng-Huat, additional, Zhai, Weiwei, additional, Hillmer, Axel M., additional, Skanderup, Anders J., additional, and Tan, Daniel S.W., additional

Published
2021
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41. Integrative Profiling of T790M-Negative EGFR-Mutated NSCLC Reveals Pervasive Lineage Transition and Therapeutic Opportunities

Author

Chua, Khi Pin, Teng, Yvonne H. F., Tan, Aaron C., Takano, Angela, Alvarez, Jacob J. S., Nahar, Rahul, Rohatgi, Neha, Lai, Gillianne G. Y., Aung, Zaw Win, Yeong, Joe P. S., Lim, Kiat Hon, Naeini, Marjan Mojtabavi, Kassam, Irfahan, Jain, Amit, Tan, Wan Ling, Gogna, Apoorva, Too, Chow Wei, Kanesvaran, Ravindran, Ng, Quan Sing, Ang, Mei Kim, Rajasekaran, Tanujaa, Anantham, Devanand, Phua, Ghee Chee, Tan, Bien Soo, Lee, Yin Yeng, Wang, Lanying, Teo, Audrey S. M., Khng, Alexis Jiaying, Lim, Ming Jie, Suteja, Lisda, Toh, Chee Keong, Lim, Wan-Teck, Iyer, N. Gopalakrishna, Tam, Wai Leong, Tan, Eng-Huat, Zhai, Weiwei, Hillmer, Axel M., Skanderup, Anders J., Tan, Daniel S. W., Chua, Khi Pin, Teng, Yvonne H. F., Tan, Aaron C., Takano, Angela, Alvarez, Jacob J. S., Nahar, Rahul, Rohatgi, Neha, Lai, Gillianne G. Y., Aung, Zaw Win, Yeong, Joe P. S., Lim, Kiat Hon, Naeini, Marjan Mojtabavi, Kassam, Irfahan, Jain, Amit, Tan, Wan Ling, Gogna, Apoorva, Too, Chow Wei, Kanesvaran, Ravindran, Ng, Quan Sing, Ang, Mei Kim, Rajasekaran, Tanujaa, Anantham, Devanand, Phua, Ghee Chee, Tan, Bien Soo, Lee, Yin Yeng, Wang, Lanying, Teo, Audrey S. M., Khng, Alexis Jiaying, Lim, Ming Jie, Suteja, Lisda, Toh, Chee Keong, Lim, Wan-Teck, Iyer, N. Gopalakrishna, Tam, Wai Leong, Tan, Eng-Huat, Zhai, Weiwei, Hillmer, Axel M., Skanderup, Anders J., and Tan, Daniel S. W.

Abstract

Purpose: Despite the established role of EGFR tyrosine kinase inhibitors (TKIs) in EGFR-mutated NSCLC, drug resistance inevitably ensues, with a paucity of treatment options especially in EGFRT790M-negative resistance. Experimental Design: We performed whole-exome and transcriptome analysis of 59 patients with first- and second-generation EGFR TKI-resistant metastatic EGFR-mutated NSCLC to characterize and compare molecular alterations mediating resistance in T790M-positive (T790M(+)) and -negative (T790M(-)) disease. Results: Transcriptomic analysis revealed ubiquitous loss of adenocarcinoma lineage gene expression in T790M(-) tumors, orthogonally validated using multiplex IHC. There was enrichment of genomic features such as TP53 alterations, 3q chromosomal amplifications, whole-genome doubling and nonaging mutational signatures in T790M(-) tumors. Almost half of resistant tumors were further classified as immune(hot), with clinical outcomes conditional on immune cell-infiltration state and T790M status. Finally, using a Bayesian statistical approach, we explored how T790M(-) and T790M(+) disease might be predicted using comprehensive genomic and transcriptomic profiles of treatment-naive patients. Conclusions: Our results illustrate the interplay between genetic alterations, cell lineage plasticity, and immune microenvironment in shaping divergent TKI resistance and outcome trajectories in EGFR-mutated NSCLC. Genomic and transcriptomic profiling may facilitate the design of bespoke therapeutic approaches tailored to a tumor's adaptive potential.

Published
2021

42. Complementary Sequential Circulating Tumor Cell (CTC) and Cell-Free Tumor DNA (ctDNA) Profiling Reveals Metastatic Heterogeneity and Genomic Changes in Lung Cancer and Breast Cancer

Author

Kong, Say Li, Liu, Xingliang, Tan, Swee Jin, Tai, Joyce A., Phua, Ler Yee, Poh, Huay Mei, Yeo, Trifanny, Chua, Yong Wei, Haw, Yu Xuan, Ling, Wen Huan, Ng, Raymond Chee Hui, Tan, Tira J., Loh, Kiley Wei Jen, Tan, Daniel Shao-Weng, Ng, Quan Sing, Ang, Mei Kim, Toh, Chee Keong, Lee, Yi Fang, Lim, Chwee Teck, Lim, Tony Kiat Hon, Hillmer, Axel M., Yap, Yoon Sim, Lim, Wan-Teck, Kong, Say Li, Liu, Xingliang, Tan, Swee Jin, Tai, Joyce A., Phua, Ler Yee, Poh, Huay Mei, Yeo, Trifanny, Chua, Yong Wei, Haw, Yu Xuan, Ling, Wen Huan, Ng, Raymond Chee Hui, Tan, Tira J., Loh, Kiley Wei Jen, Tan, Daniel Shao-Weng, Ng, Quan Sing, Ang, Mei Kim, Toh, Chee Keong, Lee, Yi Fang, Lim, Chwee Teck, Lim, Tony Kiat Hon, Hillmer, Axel M., Yap, Yoon Sim, and Lim, Wan-Teck

Abstract

Introduction Circulating tumor cells (CTCs) and cell-free tumor DNA (ctDNA) are tumor components present in circulation. Due to the limited access to both CTC enrichment platforms and ctDNA sequencing in most laboratories, they are rarely analyzed together. Methods Concurrent isolation of ctDNA and single CTCs were isolated from lung cancer and breast cancer patients using the combination of size-based and CD45-negative selection method via DropCell platform. We performed targeted amplicon sequencing to evaluate the genomic heterogeneity of CTCs and ctDNA in lung cancer and breast cancer patients. Results Higher degrees of genomic heterogeneity were observed in CTCs as compared to ctDNA. Several shared alterations present in CTCs and ctDNA were undetected in the primary tumor, highlighting the intra-tumoral heterogeneity of tumor components that were shed into systemic circulation. Accordingly, CTCs and ctDNA displayed higher degree of concordance with the metastatic tumor than the primary tumor. The alterations detected in circulation correlated with worse survival outcome for both lung and breast cancer patients emphasizing the impact of the metastatic phenotype. Notably, evolving genetic signatures were detected in the CTCs and ctDNA samples during the course of treatment and disease progression. Conclusions A standardized sample processing and data analysis workflow for concurrent analysis of CTCs and ctDNA successfully dissected the heterogeneity of metastatic tumor in circulation as well as the progressive genomic changes that may potentially guide the selection of appropriate therapy against evolving tumor clonality.

Published
2021

44. A common BIM deletion polymorphism mediates intrinsic resistance and inferior responses to tyrosine kinase inhibitors in cancer

Author

Ng, King Pan, Hillmer, Axel M., Chuah, Charles T.H., Juan, Wen Chun, Ko, Tun Kiat, Teo, Audrey S.M., Ariyaratne, Pramila N., Takahashi, Naoto, Sawada, Kenichi, Fei, Yao, Soh, Sheila, Lee, Wah Heng, Huang, John W.J., Allen, Jr., John C., Woo, Xing Yi, Nagarajan, Niranjan, Kumar, Vikrant, Thalamuthu, Anbupalam, Poh, Wan Ting, Ang, Ai Leen, Mya, Hae Tha, How, Gee Fung, Yang, Li Yi, Koh, Liang Piu, Chowbay, Balram, Chang, Chia-Tien, Nadarajan, Veera S., Chng, Wee Joo, Than, Hein, Lim, Lay Cheng, Goh, Yeow Tee, Zhang, Shenli, Poh, Dianne, Tan, Patrick, Seet, Ju-Ee, Ang, Mei-Kim, Chau, Noan-Minh, Ng, Quan-Sing, Tan, Daniel S.W., Soda, Manabu, Isobe, Kazutoshi, Nothen, Markus M., Wong, Tien Y., Shahab, Atif, Ruan, Xiaoan, Cacheux-Rataboul, Valere, Sung, Wing-Kin, Tan, Eng Huat, Yatabe, Yasushi, Mano, Hiroyuki, Soo, Ross A., Chin, Tan Min, Lim, Wan-Teck, Ruan, Yijun, and Ong, S. Tiong

Subjects
Tumor proteins -- Physiological aspects -- Genetic aspects -- Research, Antineoplastic agents -- Dosage and administration -- Genetic aspects -- Research, Genetic polymorphisms -- Physiological aspects -- Research -- Genetic aspects, Protein tyrosine kinase -- Physiological aspects -- Genetic aspects -- Research, Antimitotic agents -- Dosage and administration -- Genetic aspects -- Research, Biological sciences, Health
Abstract

Tyrosine kinase inhibitors (TKIs) elicit high response rates among individuals with kinase-driven malignancies, including chronic myeloid leukemia (CML) and epidermal growth factor receptor-mutated non-small-cell lung cancer (EGFR NSCLC). However, the [...]

Published
2012
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45. Molecular Characterization and Clinical Outcomes in RET-Rearranged NSCLC

Author

Tan, Aaron C., Seet, Amanda O.L., Lai, Gillianne G.Y., Lim, Tse Hui, Lim, Alvin S.T., Tan, Gek San, Takano, Angela, Tai, David W.M., Tan, Tira J.Y., Lam, Justina Y.C., Ng, Matthew C.H., Tan, Wan Ling, Ang, Mei-Kim, Kanesvaran, Ravindran, Ng, Quan Sing, Jain, Amit, Rajasekaran, Tanujaa, Lim, Wan-Teck, Tan, Eng-Huat, Lim, Tony Kiat Hon, and Tan, Daniel S.W.

Published
2020
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50. Phase II study of nimotuzumab ( TheraCim‐hR3 ) concurrent with cisplatin/radiotherapy in patients with locally advanced head and neck squamous cell carcinoma

Author

Ang, Mei‐Kim, primary, Montoya, Jose Enrique, additional, Tharavichitkul, Ekkasit, additional, Lim, Cindy, additional, Tan, Terence, additional, Wang, Lan Ying, additional, Wee, Joseph, additional, Soong, Yoke‐Lim, additional, Fong, Kam‐Weng, additional, Ng, Quan Sing, additional, Tan, Daniel Shao‐Weng, additional, Toh, Chee‐Keong, additional, Tan, Eng‐Huat, additional, and Lim, Wan‐Teck, additional

Published
2021
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