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      New insights into small‐cell lung cancer development and therapy

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          Abstract

          Small‐cell lung cancer (SCLC) accounts for approximately 15% of lung cancer cases; however, it is characterized by easy relapse and low survival rate, leading to one of the most intractable diseases in clinical practice. Despite decades of basic and clinical research, little progress has been made in the management of SCLC. The current standard first‐line regimens of SCLC still remain to be cisplatin or carboplatin combined with etoposide, and the adverse events of chemotherapy are by no means negligible. Besides, the immunotherapy on SCLC is still in an early stage and novel studies are urgently needed. In this review, we describe SCLC development and current therapy, aiming at providing useful advices on basic research and clinical strategy.

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          Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer

          Shang-Gin Wu, Jin-Yuan Shih (2018)
          Recent advances in diagnosis and treatment are enabling a more targeted approach to treating lung cancers. Therapy targeting the specific oncogenic driver mutation could inhibit tumor progression and provide a favorable prognosis in clinical practice. Activating mutations of epidermal growth factor receptor (EGFR) in non-small cell lung cancer (NSCLC) are a favorable predictive factor for EGFR tyrosine kinase inhibitors (TKIs) treatment. For lung cancer patients with EGFR-exon 19 deletions or an exon 21 Leu858Arg mutation, the standard first-line treatment is first-generation (gefitinib, erlotinib), or second-generation (afatinib) TKIs. EGFR TKIs improve response rates, time to progression, and overall survival. Unfortunately, patients with EGFR mutant lung cancer develop disease progression after a median of 10 to 14 months on EGFR TKI. Different mechanisms of acquired resistance to first-generation and second-generation EGFR TKIs have been reported. Optimal treatment for the various mechanisms of acquired resistance is not yet clearly defined, except for the T790M mutation. Repeated tissue biopsy is important to explore resistance mechanisms, but it has limitations and risks. Liquid biopsy is a valid alternative to tissue re-biopsy. Osimertinib has been approved for patients with T790M-positive NSCLC with acquired resistance to EGFR TKI. For other TKI-resistant mechanisms, combination therapy may be considered. In addition, the use of immunotherapy in lung cancer treatment has evolved rapidly. Understanding and clarifying the biology of the resistance mechanisms of EGFR-mutant NSCLC could guide future drug development, leading to more precise therapy and advances in treatment.
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            Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group.

            R Stephens, A. Gregor, C Le Péchoux … (1999)
            Prophylactic cranial irradiation reduces the incidence of brain metastasis in patients with small-cell lung cancer. Whether this treatment, when given to patients in complete remission, improves survival is not known. We performed a meta-analysis to determine whether prophylactic cranial irradiation prolongs survival. We analyzed individual data on 987 patients with small-cell lung cancer in complete remission who took part in seven trials that compared prophylactic cranial irradiation with no prophylactic cranial irradiation. The main end point was survival. The relative risk of death in the treatment group as compared with the control group was 0.84 (95 percent confidence interval, 0.73 to 0.97; P= 0.01), which corresponds to a 5.4 percent increase in the rate of survival at three years (15.3 percent in the control group vs. 20.7 percent in the treatment group). Prophylactic cranial irradiation also increased the rate of disease-free survival (relative risk of recurrence or death, 0.75; 95 percent confidence interval, 0.65 to 0.86; P<0.001) and decreased the cumulative incidence of brain metastasis (relative risk, 0.46; 95 percent confidence interval, 0.38 to 0.57; P<0.001). Larger doses of radiation led to greater decreases in the risk of brain metastasis, according to an analysis of four total doses (8 Gy, 24 to 25 Gy, 30 Gy, and 36 to 40 Gy) (P for trend=0.02), but the effect on survival did not differ significantly according to the dose. We also identified a trend (P=0.01) toward a decrease in the risk of brain metastasis with earlier administration of cranial irradiation after the initiation of induction chemotherapy. Prophylactic cranial irradiation improves both overall survival and disease-free survival among patients with small-cell lung cancer in complete remission.
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              Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer.

              Kazumasa Noda, Yutaka Nishiwaki, Masaaki Kawahara … (2002)
              Irinotecan hydrochloride, a topoisomerase I inhibitor, is effective against small-cell lung cancer. In a phase 2 study of irinotecan plus cisplatin in patients with extensive small-cell lung cancer, there was a high response rate and a promising median survival time. We conducted a multicenter, randomized, phase 3 study in which we compared irinotecan plus cisplatin with etoposide plus cisplatin in patients with extensive (metastatic) small-cell lung cancer. The planned size of the study population was 230 patients, but enrollment was terminated early because an interim analysis found a statistically significant difference in survival between the patients assigned to receive irinotecan and cisplatin and those assigned to receive etoposide and cisplatin; as a result, only 154 patients were enrolled. The median survival was 12.8 months in the irinotecan-plus-cisplatin group and 9.4 months in the etoposide-plus-cisplatin group (P=0.002 by the unadjusted log-rank test). At two years, the proportion of patients surviving was 19.5 percent in the irinotecan-plus-cisplatin group and 5.2 percent in the etoposide-plus-cisplatin group. Severe or life-threatening myelosuppression was more frequent in the etoposide-plus-cisplatin group than in the irinotecan-plus-cisplatin group, and severe or life-threatening diarrhea was more frequent in the irinotecan-plus-cisplatin group than in the etoposide-plus-cisplatin group. Irinotecan plus cisplatin is an effective treatment for metastatic small-cell lung cancer.
              Article 0 comments Cited 240 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Changneng Ke: kekey88@163.com
                Shi Xu:
                ORCID: http://orcid.org/0000-0002-2178-5666
                xushi_cn@163.com
                Journal
                Journal ID (nlm-ta): Cell Biol Int
                Journal ID (iso-abbrev): Cell Biol. Int
                Journal ID (doi): 10.1002/(ISSN)1095-8355
                Journal ID (publisher-id): CBIN
                Title: Cell Biology International
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1065-6995
                ISSN (Electronic): 1095-8355
                Publication date (Electronic): 18 April 2020
                Publication date (Print): August 2020
                Volume: 44
                Issue: 8 ( doiID: 10.1002/cbin.v44.8 )
                Pages: 1564-1576
                Affiliations
                [ 1 ] Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, Affiliated Central Hospital of Shenzhen Longhua District Guangdong Medical University Shenzhen Guangdong China
                [ 2 ] Division of Respiratory Medicine, Department of Medicine, The University of Hong Kong Queen Mary Hospital Hong Kong SAR China
                Author notes
                [*] [* ] Correspondence

                Changneng Ke and Shi Xu, Department of Burn and Plastic Surgery, Shenzhen Longhua District Central Hospital, Affiliated Central Hospital of Shenzhen Longhua District, Guangdong Medical University, Shenzhen, Guangdong 518110, China.

                Email: kekey88@ 123456163.com (C. K.) and xushi_cn@ 123456163.com (S. X.)

                Author information
                http://orcid.org/0000-0002-2178-5666
                Article
                Publisher ID: CBIN11359
                DOI: 10.1002/cbin.11359
                PMC ID: 7496722
                PubMed ID: 32281704
                SO-VID: 30e4de5f-2ff1-4074-ab61-a403eedc7769
                Copyright © © 2020 The Authors. Cell Biology International published by John Wiley & Sons Ltd on behalf of International Federation of Cell Biology
                License:

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 31 December 2019
                Date revision received : 24 February 2020
                Date accepted : 11 April 2020
                Page count
                Figures: 1, Tables: 4, Pages: 13, Words: 11320
                Funding
                Funded by: Shenzhen Longhua District Science and Innovation Bureau, special fund for the second batch of healthcare in 2017
                Award ID: 2017136
                Funded by: Shenzhen Longhua District Science and Innovation Bureau for Key Laboratory Construction
                Award ID: 20160919A0410022
                Categories
                Subject: Review
                Subject: Reviews
                Custom metadata
                source-schema-version-number 2.0
                cover-date August 2020
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.0 mode:remove_FC converted:11.09.2020

                ScienceOpen disciplines: Cell biology
                Keywords: lung morphogenesis,small‐cell lung cancer,therapy
                Data availability:
                ScienceOpen disciplines: Cell biology
                Keywords: lung morphogenesis, small‐cell lung cancer, therapy

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