Non-Small Cell Lung Cancer from Genomics to Therapeutics: A Framework for Community Practice Integration to Arrive at Personalized Therapy Strategies

Rajurkar, Swapnil; Mambetsariev, Isa; Pharaon, Rebecca; Leach, Benjamin I.; Tan, Tingting; Kulkarni, Prakash; Salgia, Ravi

doi:10.3390/jcm9061870

Cited by 19 publications

(18 citation statements)

References 187 publications

(280 reference statements)

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“…Thus, building the workflow infrastructure to support the use of pathway tools which include increasingly higher cost therapies can also support more timely authorization of treatments for patients and can help to engage early patient assistance, when needed, so patients can receive timely care which improves outcomes [ 46 , 47 ]. Several examples of the growing complexity of high-quality care are described in companion articles on colorectal and non-small cell lung cancer by colleagues in this series [ 48 , 49 ].…”

Section: Nccn Guidelines and Growing Complexity Of Evidence-based mentioning

confidence: 99%

Integrating Academic and Community Cancer Care and Research through Multidisciplinary Oncology Pathways for Value-Based Care: A Review and the City of Hope Experience

Bosserman

Cianfrocca

Yuh

et al. 2021

JCM

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As the US transitions from volume- to value-based cancer care, many cancer centers and community groups have joined to share resources to deliver measurable, high-quality cancer care and clinical research with the associated high patient satisfaction, provider satisfaction, and practice health at optimal costs that are the hallmarks of value-based care. Multidisciplinary oncology care pathways are essential components of value-based care and their payment metrics. Oncology pathways are evidence-based, standardized but personalizable care plans to guide cancer care. Pathways have been developed and studied for the major medical, surgical, radiation, and supportive oncology disciplines to support decision-making, streamline care, and optimize outcomes. Implementing multidisciplinary oncology pathways can facilitate comprehensive care plans for each cancer patient throughout their cancer journey and across large multisite delivery systems. Outcomes from the delivered pathway-based care can then be evaluated against individual and population benchmarks. The complexity of adoption, implementation, and assessment of multidisciplinary oncology pathways, however, presents many challenges. We review the development and components of value-based cancer care and detail City of Hope’s (COH) academic and community-team-based approaches for implementing multidisciplinary pathways. We also describe supportive components with available results towards enterprise-wide value-based care delivery.

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Section: Nccn Guidelines and Growing Complexity Of Evidence-based mentioning

confidence: 99%

Integrating Academic and Community Cancer Care and Research through Multidisciplinary Oncology Pathways for Value-Based Care: A Review and the City of Hope Experience

Bosserman

Cianfrocca

Yuh

et al. 2021

JCM

Self Cite

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“…Current therapeutics, such as surgery, chemotherapeutic agents, and targeting and immune therapies, have significantly improved the survival rate of patients with lung cancer. However, most patients diagnosed in the advanced metastatic stage still have a very low overall survival rate (2). Thus, developing novel effective targeted treatments is a crucial step in lung cancer therapy (3).…”

Section: Introductionmentioning

confidence: 99%

SENP1 inhibition suppresses the growth of lung cancer cells through activation of A20-mediated ferroptosis

Gao¹,

Xiao²,

Zhang³

et al. 2022

Ann Transl Med

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Background: Ferroptosis is a type of cell death driven by iron accumulation and lipid peroxidation, which is involved in the pathogenesis of various tumors. Small ubiquitin-like modifier (SUMO)-specific protease 1 (SENP1) is a critical SUMO-specific protease, which controls multiple cellular signaling processes. However, the roles and mechanisms of SENP1-mediated protein SUMOylation in the regulation of cell death and ferroptosis remain unexplored. Methods:The gene expression of SENP1 and ferroptosis-related genes in samples of lung cancer patient and cells were determined by immunohistochemical staining, real-time polymerase chain reaction (RT-qPCR) and Western blot. The association of gene expression with the survival rate of lung cancer patients was analyzed from public database. The erastin and cisplatin was used to induce ferroptosis, and cell ferroptosis were determined by evaluated lipid-reactive oxygen species (ROS), cell viability and electron microscopy.The protein interaction was determined by immunoprecipitation (IP) and shotgun proteomics analysis. An in vivo tumor transplantation model of immunodeficient mice was used to evaluate the effect of SENP1 on tumor growth in vivo.Results: SENP1 is aberrantly overexpressed in lung cancer cells and is associated with the low survival rate of patients. SENP1 inhibition by short hairpin RNA transduction or a specific inhibitor suppressed the proliferation and growth of lung cancer cells both in vitro and in vivo. SENP1 overexpression protected lung cancer cells from ferroptosis induced by erastin or cisplatin. Transcriptome and proteomics profiles revealed the involvement of SUMOylation regulation of the inflammation signal A20 in SENP1 inhibition-induced ferroptosis. Functional studies proved that A20 functions as a positive inducer and enhances the ferroptosis of A549 cells. A20 was shown to interact with ACSL4 and SLC7A11 to regulate the ferroptosis of lung cancer cells.Conclusions: SENP1 was identified as a suppressor of ferroptosis through a novel network of A20 SUMOylation links ACSL4 and SLC7A11 in lung cancer cells. SENP1 inhibition promotes ferroptosis and apoptosis and represents a novel therapeutic target for lung cancer therapy.

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“…Lung cancer remains one of the fatal causes of cancer related malignancies in the world with non-small cell lung cancer (NSCLC) accounting for 85% of cases [ 1 ]. NSCLC encompasses numerous subtypes, including lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) and despite advances in diagnosis, 70% of patients present with metastatic lung cancer disease when surgery is not an option [ 2 ]. Receptor tyrosine kinases (RTKs) have emerged as critical players of cellular communication function and network.…”

Section: Introductionmentioning

confidence: 99%

Identification of Flavonoids as Putative ROS-1 Kinase Inhibitors Using Pharmacophore Modeling for NSCLC Therapeutics

et al. 2021

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Non-small cell lung cancer (NSCLC) is a lethal non-immunogenic malignancy and proto-oncogene ROS-1 tyrosine kinase is one of its clinically relevant oncogenic markers. The ROS-1 inhibitor, crizotinib, demonstrated resistance due to the Gly2032Arg mutation. To curtail this resistance, researchers developed lorlatinib against the mutated kinase. In the present study, a receptor-ligand pharmacophore model exploiting the key features of lorlatinib binding with ROS-1 was exploited to identify inhibitors against the wild-type (WT) and the mutant (MT) kinase domain. The developed model was utilized to virtually screen the TimTec flavonoids database and the retrieved drug-like hits were subjected for docking with the WT and MT ROS-1 kinase. A total of 10 flavonoids displayed higher docking scores than lorlatinib. Subsequent molecular dynamics simulations of the acquired flavonoids with WT and MT ROS-1 revealed no steric clashes with the Arg2032 (MT ROS-1). The binding free energy calculations computed via molecular mechanics/Poisson-Boltzmann surface area (MM/PBSA) demonstrated one flavonoid (Hit) with better energy than lorlatinib in binding with WT and MT ROS-1. The Hit compound was observed to bind in the ROS-1 selectivity pocket comprised of residues from the β-3 sheet and DFG-motif. The identified Hit from this investigation could act as a potent WT and MT ROS-1 inhibitor.

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Non-Small Cell Lung Cancer from Genomics to Therapeutics: A Framework for Community Practice Integration to Arrive at Personalized Therapy Strategies

Cited by 19 publications

References 187 publications

Integrating Academic and Community Cancer Care and Research through Multidisciplinary Oncology Pathways for Value-Based Care: A Review and the City of Hope Experience

Integrating Academic and Community Cancer Care and Research through Multidisciplinary Oncology Pathways for Value-Based Care: A Review and the City of Hope Experience

SENP1 inhibition suppresses the growth of lung cancer cells through activation of A20-mediated ferroptosis

Identification of Flavonoids as Putative ROS-1 Kinase Inhibitors Using Pharmacophore Modeling for NSCLC Therapeutics

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