Patient-derived Xenograft Models of Small Cell Lung Cancer for Therapeutic Development

Vidhyasagar, V; Haq, Sami Ul; Lok, Benjamin H.

doi:10.1016/j.clon.2020.05.017

Cited by 6 publications

(2 citation statements)

References 59 publications

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“…Furthermore, PDX tumors are often extensively characterized, thus enabling more complex studies of drug resistance and treatment response. 28 However, a number of known challenges exist with these models. While hundreds of these lines exist, some tumor histotypes, such as prostate cancer and a range of hematological malignancies, are considerably more challenging to establish.…”

Section: Introductionmentioning

confidence: 99%

Immuno-oncology trends: preclinical models, biomarkers, and clinical development

Franklin

Platero

Saini

et al. 2022

J Immunother Cancer

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The landscape in immuno-oncology (I-O) has undergone profound changes since its early beginnings up through the rapid advances happening today. The current drug development pipeline consists of thousands of potential I-O therapies and therapy combinations, many of which are being evaluated in clinical trials. The efficient and successful development of these assets requires the investment in and utilization of appropriate tools and technologies that can facilitate the rapid transitions from preclinical evaluation through clinical development. These tools include (i) appropriate preclinical models, (ii) biomarkers of pharmacodynamic, predictive and monitoring utility, and (iii) evolving clinical trial designs that allow rapid and efficient evaluation during the development process. This article provides an overview of how novel discoveries and insights into each of these three areas have the potential to further address the clinical management needs for patients with cancer.

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Section: Introductionmentioning

confidence: 99%

Immuno-oncology trends: preclinical models, biomarkers, and clinical development

Franklin

Platero

Saini

et al. 2022

J Immunother Cancer

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“…In SCLC following relapse, CTCs are relatively more accessible than biopsy samples and have been essential to generate a cohort of matched PDX pairs to discover chemotherapy escape mechanisms ( 22 ). PDX models of SCLC retain the histological features and genomic alterations of the original tumor, and they exhibit sensitivity to first-line EP that reflects the clinical history of the donor patients ( 21 , 23 , 24 ). In parallel, we conducted a single-arm phase 1/2 trial of combination therapy with the poly(adenosine diphosphate–ribose) polymerase (PARP) inhibitor olaparib plus the DNA alkylating agent temozolomide (TMZ; combination OT) in patients with relapsed SCLC.…”

Section: Introductionmentioning

confidence: 99%

Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer

et al. 2022

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In small cell lung cancer (SCLC), acquired resistance to DNA-damaging therapy is challenging to study because rebiopsy is rarely performed. We used patient-derived xenograft models, established before therapy and after progression, to dissect acquired resistance to olaparib plus temozolomide (OT), a promising experimental therapy for relapsed SCLC. These pairs of serial models reveal alterations in both cell cycle kinetics and DNA replication and demonstrate both inter- and intratumoral heterogeneity in mechanisms of resistance. In one model pair, up-regulation of translesion DNA synthesis (TLS) enabled tolerance of OT-induced damage during DNA replication. TLS inhibitors restored sensitivity to OT both in vitro and in vivo, and similar synergistic effects were seen in additional SCLC cell lines. This represents the first described mechanism of acquired resistance to DNA damage in a patient with SCLC and highlights the potential of the serial model approach to investigate and overcome resistance to therapy in SCLC.

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A nanotechnology driven effectual localized lung cancer targeting approaches using tyrosine kinases inhibitors: Recent progress, preclinical assessment, challenges, and future perspectives

Kumar,

Vaiphei,

Gulbake

2024

International Journal of Pharmaceutics

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Patient-derived Xenograft Models of Small Cell Lung Cancer for Therapeutic Development

Abstract: Clinical Oncology j o ur n a l h o m e p a ge : w w w . c l i n i c a l on c o l o gy o n l i ne . n e t

Cited by 6 publications

References 59 publications

Immuno-oncology trends: preclinical models, biomarkers, and clinical development

Immuno-oncology trends: preclinical models, biomarkers, and clinical development

Translesion DNA synthesis mediates acquired resistance to olaparib plus temozolomide in small cell lung cancer

A nanotechnology driven effectual localized lung cancer targeting approaches using tyrosine kinases inhibitors: Recent progress, preclinical assessment, challenges, and future perspectives

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