Carfilzomib (CFZ), carboplatin and etoposide for previously untreated extensive-stage small cell lung cancer (ES-SCLC): Phase 1b results from a phase 1b/2 study.

Badin, Firas; Chiang, Anne C.; Fisher, William B.; Orlov, Sergey; Harper, Harry; Eskander, E.; Harb, Wael A.; Kio, Ebenezer A.; Gopalan, Priya; Haggstrom, Daniel; Burdaeva, Olga; Zahlten-Kumeli, Anita; Aggarwal, Sanjay; Obreja, Mihaela; Gorbunova, Vera

doi:10.1200/jco.2016.34.15_suppl.e20092

Cited by 2 publications

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“…Further, carfilzomib, marizomib, MLN9708, and salinosporamide have also been developed as proteasome inhibitors and are under clinical trials for the treatment of chronic lymphocytic lymphoma, myeloma bone disease, and multiple myeloma [200,210,211,212,213,214,215]. Interestingly, carfilzomib was applied in combination with carboplatin and etoposide in a clinical trial for relapsed small-cell lung cancer [216].…”

Section: Targeting the Upr In Cancermentioning

confidence: 99%

Proteostasis in the Endoplasmic Reticulum: Road to Cure

Nam

Jeon

2019

Cancers

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The endoplasmic reticulum (ER) is an interconnected organelle that is responsible for the biosynthesis, folding, maturation, stabilization, and trafficking of transmembrane and secretory proteins. Therefore, cells evolve protein quality-control equipment of the ER to ensure protein homeostasis, also termed proteostasis. However, disruption in the folding capacity of the ER caused by a large variety of pathophysiological insults leads to the accumulation of unfolded or misfolded proteins in this organelle, known as ER stress. Upon ER stress, unfolded protein response (UPR) of the ER is activated, integrates ER stress signals, and transduces the integrated signals to relive ER stress, thereby leading to the re-establishment of proteostasis. Intriguingly, severe and persistent ER stress and the subsequently sustained unfolded protein response (UPR) are closely associated with tumor development, angiogenesis, aggressiveness, immunosuppression, and therapeutic response of cancer. Additionally, the UPR interconnects various processes in and around the tumor microenvironment. Therefore, it has begun to be delineated that pharmacologically and genetically manipulating strategies directed to target the UPR of the ER might exhibit positive clinical outcome in cancer. In the present review, we summarize recent advances in our understanding of the UPR of the ER and the UPR of the ER–mitochondria interconnection. We also highlight new insights into how the UPR of the ER in response to pathophysiological perturbations is implicated in the pathogenesis of cancer. We provide the concept to target the UPR of the ER, eventually discussing the potential of therapeutic interventions for targeting the UPR of the ER for cancer treatment.

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Section: Targeting the Upr In Cancermentioning

confidence: 99%

Proteostasis in the Endoplasmic Reticulum: Road to Cure

Nam

Jeon

2019

Cancers

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“…The combination was quite toxic with 75% of patients having grade three or four adverse effects. Preliminary efficacy results included ORR of 16/30 (53.3%) and median PFS of 4.4 months (95% CI 3.2–5.8) [83].…”

Section: Epigenetic Targetingmentioning

confidence: 99%

Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

Lum

Alamgeer

2019

Cancers

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Small cell lung cancer (SCLC) accounts for approximately 10–15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.

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Carfilzomib (CFZ), carboplatin and etoposide for previously untreated extensive-stage small cell lung cancer (ES-SCLC): Phase 1b results from a phase 1b/2 study.

Cited by 2 publications

References 0 publications

Proteostasis in the Endoplasmic Reticulum: Road to Cure

Proteostasis in the Endoplasmic Reticulum: Road to Cure

Technological and Therapeutic Advances in Advanced Small Cell Lung Cancer

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