What's New in SCLC? A Review

A few years ago the answer to the question in the title of this review would have been, “unfortunately not much” or even “nothing”, likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of th...

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Vydáno v:Neoplasia (New York, N.Y.) Ročník 19; číslo 10; s. 842 - 847
Hlavní autoři: Oronsky, Bryan, Reid, Tony R., Oronsky, Arnold, Carter, Corey A.
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Elsevier Inc 01.10.2017
Elsevier Limited
Neoplasia Press
Elsevier
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ISSN:1476-5586, 1522-8002, 1476-5586, 1522-8002
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Abstract A few years ago the answer to the question in the title of this review would have been, “unfortunately not much” or even “nothing”, likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals. However, a paradigm shift or, more appropriately, a ‘paradigm nudge’ is quietly underway in extensive stage SCLC with a series of agents that in early clinical trials have shown the potential to ‘lift the curse’ in SCLC, heretofore referred to as “a graveyard for drug development”. These agents, constituting the “best of what's new” in SCLC, and discussed in this review following a brief overview of the classification, epidemiology, prognosis and current treatment of SCLC, include checkpoint inhibitors, antibody-drug conjugates, PARP inhibitors, epigenetic inhibitor/innate immune activator, and an inhibitor of RNA polymerase II. Compared to NSCLC, the therapeutic options are still limited but with one or more successes to build momentum and drive long-overdue R&D and clinical investment the hope is that the approval floodgates may finally open.
AbstractList A few years ago the answer to the question in the title of this review would have been, “unfortunately not much” or even “nothing”, likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals. However, a paradigm shift or, more appropriately, a ‘paradigm nudge’ is quietly underway in extensive stage SCLC with a series of agents that in early clinical trials have shown the potential to ‘lift the curse’ in SCLC, heretofore referred to as “a graveyard for drug development”. These agents, constituting the “best of what's new” in SCLC, and discussed in this review following a brief overview of the classification, epidemiology, prognosis and current treatment of SCLC, include checkpoint inhibitors, antibody-drug conjugates, PARP inhibitors, epigenetic inhibitor/innate immune activator, and an inhibitor of RNA polymerase II. Compared to NSCLC, the therapeutic options are still limited but with one or more successes to build momentum and drive long-overdue R&D and clinical investment the hope is that the approval floodgates may finally open.
A few years ago the answer to the question in the title of this review would have been, "unfortunately not much" or even "nothing", likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals. However, a paradigm shift or, more appropriately, a 'paradigm nudge' is quietly underway in extensive stage SCLC with a series of agents that in early clinical trials have shown the potential to 'lift the curse' in SCLC, heretofore referred to as "a graveyard for drug development". These agents, constituting the "best of what's new" in SCLC, and discussed in this review following a brief overview of the classification, epidemiology, prognosis and current treatment of SCLC, include checkpoint inhibitors, antibody-drug conjugates, PARP inhibitors, epigenetic inhibitor/innate immune activator, and an inhibitor of RNA polymerase II. Compared to NSCLC, the therapeutic options are still limited but with one or more successes to build momentum and drive long-overdue R&D and clinical investment the hope is that the approval floodgates may finally open.A few years ago the answer to the question in the title of this review would have been, "unfortunately not much" or even "nothing", likely eliciting knowing nods of agreement from oncologists. For the last 3 decades, SCLC has been notorious for its lack of progress, as drug after drug, over 60 of them, in fact, including inhibitors of VEGF, IGFR, mTOR, EGFR and HGF has failed and fallen by the wayside due to little or no impact on PFS or OS, while SCLC's cousin, NSCLC, has notched success after success with a spate of targeted treatment and immunotherapy regulatory approvals. However, a paradigm shift or, more appropriately, a 'paradigm nudge' is quietly underway in extensive stage SCLC with a series of agents that in early clinical trials have shown the potential to 'lift the curse' in SCLC, heretofore referred to as "a graveyard for drug development". These agents, constituting the "best of what's new" in SCLC, and discussed in this review following a brief overview of the classification, epidemiology, prognosis and current treatment of SCLC, include checkpoint inhibitors, antibody-drug conjugates, PARP inhibitors, epigenetic inhibitor/innate immune activator, and an inhibitor of RNA polymerase II. Compared to NSCLC, the therapeutic options are still limited but with one or more successes to build momentum and drive long-overdue R&D and clinical investment the hope is that the approval floodgates may finally open.
Author Oronsky, Arnold
Oronsky, Bryan
Reid, Tony R.
Carter, Corey A.
AuthorAffiliation InterWest Partners, 2710 Sand Hill Road #200, Menlo Park, CA 94025, USA
Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889, USA
EpicentRx Inc, 4445 Eastgate Mall, Suite 200, San Diego, CA 92121, USA
University of California San Diego, Moores Cancer Center, 3855 Health Sciences Dr, La Jolla, CA 92093, USA
AuthorAffiliation_xml – name: University of California San Diego, Moores Cancer Center, 3855 Health Sciences Dr, La Jolla, CA 92093, USA
– name: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889, USA
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– sequence: 2
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  surname: Reid
  fullname: Reid, Tony R.
  organization: University of California San Diego, Moores Cancer Center, 3855 Health Sciences Dr, La Jolla, CA 92093, USA
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  surname: Oronsky
  fullname: Oronsky, Arnold
  organization: InterWest Partners, 2710 Sand Hill Road #200, Menlo Park, CA 94025, USA
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  givenname: Corey A.
  surname: Carter
  fullname: Carter, Corey A.
  organization: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD 20889, USA
BackLink https://www.ncbi.nlm.nih.gov/pubmed/28888101$$D View this record in MEDLINE/PubMed
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Snippet A few years ago the answer to the question in the title of this review would have been, “unfortunately not much” or even “nothing”, likely eliciting knowing...
A few years ago the answer to the question in the title of this review would have been, "unfortunately not much" or even "nothing", likely eliciting knowing...
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SubjectTerms Clinical trials
DNA-directed RNA polymerase
Drug development
Epidemiology
Epidermal growth factor receptors
Humans
Immune checkpoint
Immunotherapy
Lung Neoplasms - diagnosis
Lung Neoplasms - epidemiology
Lung Neoplasms - etiology
Lung Neoplasms - therapy
Molecular Targeted Therapy
Neoplasm Staging
Non-small cell lung carcinoma
Poly(ADP-ribose) polymerase
Prevalence
Prognosis
Review article
Reviews
RNA polymerase
Small cell lung carcinoma
Small Cell Lung Carcinoma - diagnosis
Small Cell Lung Carcinoma - epidemiology
Small Cell Lung Carcinoma - etiology
Small Cell Lung Carcinoma - therapy
TOR protein
Treatment Outcome
Vascular endothelial growth factor
Title What's New in SCLC? A Review
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https://dx.doi.org/10.1016/j.neo.2017.07.007
https://www.ncbi.nlm.nih.gov/pubmed/28888101
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https://pubmed.ncbi.nlm.nih.gov/PMC5596356
https://doaj.org/article/c90338acb376476f948b9e2e9c334510
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