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Application of an ex-vivo drug sensitivity platform towards achieving complete remission in a refractory T-cell lymphoma

作者:Sanjay De Mel, Masturah Bte Mohd Abdul Rashid, Xi Yun Zhang, Jasmine Goh, Chun Tsu Lee, Li Mei Poon, Esther Hian Li Chan, Xin Liu, Wee Joo Chng, Yen Lin Chee, Joanne Lee, Yi Ching Yuen, Jing Quan Lim, Burton Kuan Hui Chia, Yurike Laurensia, Dachuan Huang, Wan Lu Pang, Daryl Ming Zhe Cheah, Esther Kam Yin Wong, Choon Kiat Ong, Tiffany Tang, Soon Thye Lim, Siok‐Bian Ng, Soo‐Yong Tan, Hoi-Yin Loi, Lip Kun Tan, Edward Kai‐Hua Chow, Anand D. Jeyasekharan · 发表于:Blood Cancer Journal · 年份:2020 · DOI:10.1038/s41408-020-0276-7 · 被引用次数:38 · 研究领域:Lymphoma Diagnosis and Treatment、CAR-T cell therapy research、Chronic Lymphocytic Leukemia Research

Currently, there are no clinically approved methods for predicting the relative efficacy of drug combinations for individual patients with cancer. Ex-vivo drug sensitivity experiments with patient-derived tumor material potentially offers a solution to identifying appropriate combinations of therapies for individual patients 1 . However, such assays are typically limited by the quantity available for combinatorial analysis of multiple drugs. We recently developed an experimental–analytical hybrid method, Quadratic phenotypic optimization platform (QPOP), which ranks drug combinations using a limited amount of tumor 2 . QPOP identifies optimal combinations based on the observation that biological response to perturbations (such as therapeutic intervention) can be mapped to a second-order polynomial equation 3 . In our initial study, QPOP identified novel therapeutic combinations for drug-resistant multiple myeloma, using ex-vivo testing on primary tumor samples. However, the concordance of QPOP-based drug sensitivity prediction with actual patient response to treatment was not explored in that study. We now present a case illustrating the setup and utilization of a QPOP protocol as a clinical decision aid, to identify an optimal salvage regimen for a patient with refractory lymphoma.