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drug-adapted cancer cell lines as preclinical models of acquired resistance

Cancer drug resistance 2019年第3期2卷 447-456页

作者： Martin Michaelis Mark N.Wass Jindrich Cinatl jr School of Biosciences University of KentCanterbury CT27NJUK Institut für Medizinische Virologie Klinikum der Goethe-UniversitätFrankfurt am MainGermany.

acquired resistance formation limits the efficacy of anti-cancer *** and intrinsic resistance differ *** resistance is the consequence of directed evolution,whereas intrinsic resistance depends on the(stochastic)presence of pre-existing resistance *** model systems are needed to study acquired drug resistance because they enable:(1)in depth functional studies;(2)the investigation of non-standard treatments for a certain disease condition(which is necessary to identify small groups of responders);and(3)the comparison of multiple therapies in the same ***,they complement data derived from clinical trials and clinical specimens,including liquid *** groups have successfully used drug-adapted cancer cell lines to identify and elucidate clinically relevant resistance mechanisms to targeted and cytotoxic anti-cancer ***,we argue that drug-adapted cancer cell lines represent a preclinical model system in their own right that is complementary to other preclinical model systems and clinical data.

关键词： Cancer acquired drug resistance cancer cell lines drug adaptation cancer therapy cancer models

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New insights from the widening homogeneity perspective to target intratumor heterogeneity

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Cancer Communications 2018年第1期38卷 195-201页

作者： Mengying Tong Ziqian Deng Xiaolong Zhang Bin He Mengying Yang Wei Cheng Quentin Liu Institute of Cancer Stem Cell Cancer CenterDalian Medical UniversityDalian 116044LiaoningP.R.China State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer CenterGuangzhou 510630GuangdongP.R.China Department of Hematology The Third Affiliated HospitalSun Yat-sen UniverisityGuangzhou 510630GuangdongP.R.China

Precision medicine has shed new light on the treatment of heterogeneous cancer ***,intratumor heterogeneity strongly constrains the clinical benefit of precision ***,rethinking therapeutic strategies from a different facet within the precision medicine framework will not only diversify clinical interventions,but also provide an avenue for precision ***,we explore the current approaches for targeting intratumor hetero-geneity and their ***,we propose a theoretical strategy with a“homogenization”feature based on iatrogenic evolutionary selection to target intratumor heterogeneity.

关键词： acquired drug resistance Homogenization Intratumor heterogeneity Plasticity Precision medicine

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Approaches to identifying drug resistance mechanisms to clinically relevant treatments in childhood rhabdomyosarcoma

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Cancer drug resistance 2022年第1期5卷 80-89页

作者： Samson Ghilu Christopher L.Morton Angelina V.Vaseva Siyuan Zheng Raushan T.Kurmasheva Peter J.Houghton Department of Molecular Medicine Greehey Children’s Cancer Research InstituteUT HealthSan AntonioTX 78229USA Department of Surgery St.Jude Children’s Research HospitalMemphisTN 38105USA Department of Epidemiology and Biostatistics Greehey Children’s Cancer Research InstituteUT HealthSan AntonioTX 78229USA

Aim:Despite aggressive multiagent protocols,patients with metastatic rhabdomyosarcoma(RMS)have poor *** a recent high-risk trial(ARST0431),25% of patients failed within the first year,while on therapy and 80% had tumor progression within 24 ***,the mechanisms for tumor resistance are essentially *** we explore the use of preclinical models to develop resistance to complex chemotherapy regimens used in ***:A Single Mouse Testing(SMT)protocol was used to evaluate the sensitivity of 34 RMS xenograft models to one cycle of vincristine,actinomycin D,cyclophosphamide(VAC)*** response was determined by caliper measurement,and tumor regression and event-free survival(EFS)were used as endpoints for *** tumors at regrowth were transplanted into recipient mice,and the treatment was repeated until tumors progressed during the treatment period(i.e.,became resistant).At transplant,tumor tissue was stored for biochemical and omics ***:The sensitivity to VAC of 34 RMS models was *** varied from 3 weeks to>20 *** models were classified as having intrinsic resistance,intermediate sensitivity,or high sensitivity to VAC *** to VAC was developed in multiple models after 2-5 cycles of therapy;however,there were examples where sensitivity remained unchanged after 3 cycles of ***:The SMT approach allows for in vivo assessment of drug sensitivity and development of drug resistance in a large number of RMS *** such,it provides a platform for assessing in vivo drug resistance mechanisms at a“population”level,simulating conditions in vivo that lead to clinical *** VAC-resistant models represent“high-risk”tumors that mimic a preclinical phase 2 population and will be valuable for identifying novel agents active against VAC-resistant disease.

关键词： Rhabdomyosarcoma patient-derived xenografts combination therapy intrinsic drug resistance acquired drug resistance

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