Emerging therapies for small cell lung cancer

Yang, Sen; Zhang, Zhe; Wang, Qiming

doi:10.1186/s13045-019-0736-3

Cited by 297 publications

(252 citation statements)

References 70 publications

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“…In contrast, further subclassifying small cell lung cancer (SCLC) has fewer diagnostic consequence, as it is sufficient to correctly determine the small cell histology in order to initiate chemotherapeutic treatment [5]. Ongoing clinical trials are evaluating targeted and immunotherapies for molecularly characterized SCLCs, yet none of these are routinely implemented at present [6].…”

Section: (Continued From Previous Page)mentioning

confidence: 99%

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

et al. 2020

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Background: Accurate lung cancer classification is crucial to guide therapeutic decisions. However, histological subtyping by pathologists requires tumor tissue-a necessity that is often intrinsically associated with procedural difficulties. The analysis of circulating tumor DNA present in minimal-invasive blood samples, referred to as liquid biopsies, could therefore emerge as an attractive alternative. Methods: Concerning adenocarcinoma, squamous cell carcinoma, and small cell carcinoma, our proof of concept study investigates the potential of liquid biopsy-derived copy number alterations, derived from single-end shallow whole-genome sequencing (coverage 0.1-0.5×), across 51 advanced stage lung cancer patients. Results: Genomic abnormality testing reveals anomalies in 86.3% of the liquid biopsies (16/20 for adenocarcinoma, 13/16 for squamous cell, and 15/15 for small cell carcinoma). We demonstrate that copy number profiles from formalin-fixed paraffin-embedded tumor biopsies are well represented by their liquid equivalent. This is especially valid within the small cell carcinoma group, where paired profiles have an average Pearson correlation of 0.86 (95% CI 0.79-0.93). A predictive model trained with public data, derived from 843 tissue biopsies, shows that liquid biopsies exhibit multiple deviations that reflect histological classification. Most notably, distinguishing small from non-small cell lung cancer is characterized by an area under the curve of 0.98 during receiver operating characteristic analysis. Additionally, we investigated how deeper paired-end sequencing, which will eventually become feasible for routine diagnosis, empowers tumor read enrichment by insert size filtering: for all of the 29 resequenced liquid biopsies, the tumor fraction could be increased in silico, thereby "rescuing" three out of five cases with previously undetectable alterations.(Continued on next page)

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Section: (Continued From Previous Page)mentioning

confidence: 99%

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

et al. 2020

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“…[12][13][14] Anlotinib has encouraging antitumor effects and acceptable toxicity in advanced lung adenocarcinoma, lung squamous cell carcinoma, STS, medullary thyroid cancer, small cell lung cancer and metastatic renal clear cell cancer. [15][16][17][18] A Phase II clinical trial showed that a total of 166 relapsed advanced STS patients had a significant survival benefit after treatment with anlotinib, with a 12-week progressionfree rate of 68.42% and an objective response rate of 12.65%. The PFS and OS were 5.63 and 12.33 months, respectively.…”

Section: Introductionmentioning

confidence: 99%

<p>Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma</p>

Wang

Chu

Zhang

et al. 2020

OTT

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Purpose: Anlotinib, a newly developed oral small-molecule receptor tyrosine kinase inhibitor (TKI), has been shown to have encouraging activity against sarcoma. The purpose of this study was to retrospectively evaluate the safety and clinical efficacy of chemotherapy combined with anlotinib plus anlotinib maintenance in advanced/metastatic soft tissue sarcoma (STS) patients in a real-world setting in China. Patients and Methods: We retrospectively collected the medical data of thirty-two patients with advanced/metastatic STS who received chemotherapy combined with anlotinib plus anlotinib maintenance therapy. The objective response rate (ORR) and disease control rate (DCR) were calculated according to the RECIST 1.1 criteria. The progression-free rates (PFRs) at three and six months, the progression-free survival (PFS) time, and adverse events were recorded. Results: On the basis of investigator assessments, two patients (6%) achieved CR (complete response) and nine patients (28%) achieved PR (partial response), with an ORR of 34%. Eleven patients (34%) achieved SD (stable disease), and ten patients (31%) achieved PD (progression disease), with a DCR of 69%. The progression-free rates (PFRs) at three and six months were 81% and 69%, respectively. The median PFS time was 8.2 months. The hematologic and non-hematologic toxicities were manageable. The most common grade 3 and 4 adverse events were febrile neutropenia (9%), leukopenia (19%), thrombocytopenia (3%), anemia (6%), anorexia (6%), vomiting (3%), and hypertension (6%). The combination therapy was generally well tolerated. Conclusion: Our study suggests that chemotherapy combined with anlotinib plus anlotinib maintenance therapy had good efficacy and resulted in more favorable survival with good tolerance among patients with advanced/metastatic STS.

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“…The discoveries of PD1 and PD-L1 have led to the revolution of modern cancer immunotherapy [51]. Multiple agents targeting PD1, PD-L1, or CTLA-4 either as single agent or combination regimens are widely used as ICIs which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancer cells [52][53][54][55]. Recent discoveries on the immunomodulatory effects of gut microbiota shed lights on new ways in enhancing cancer immunotherapy [56].…”

Section: Immune Checkpoint Inhibitors (Ici): Targeting Tumor Microenvmentioning

confidence: 99%

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

Liu

2019

J Hematol Oncol

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New advances in the design and manufacture of monoclonal antibodies, bispecific T cell engagers, and antibodydrug conjugates make the antibody-directed agents more powerful with less toxicities. Small molecule inhibitors are routinely used now as oral targeted agents for multiple cancers. The discoveries of PD1 and PD-L1 as negative immune checkpoints for T cells have led to the revolution of modern cancer immunotherapy. Multiple agents targeting PD1, PD-L1, or CTLA-4 are widely applied as immune checkpoint inhibitors (ICIs) which alleviate the suppression of immune regulatory machineries and lead to immunoablation of once highly refractory cancers such as stage IV lung cancer. Tisagenlecleucel and axicabtagene ciloleucel are the two approved CD19-targeted chimeric antigen receptor (CAR) T cell products. Several CART cell platforms targeting B cell maturation antigen (BCMA) are under active clinical trials for refractory and/or relapsed multiple myeloma. Still more targets such as CLL-1, EGFR, NKG2D and mesothelin are being directed in CART cell trials for leukemia and solid tumors. Increasing numbers of novel agents are being studied to target cancer-intrinsic oncogenic pathways as well as immune checkpoints. One such an example is targeting CD47 on macrophages which represents a "do-not-eat-me" immune checkpoint. Fueling the current excitement of cancer medicine includes also TCR-T cells, TCR-like antibodies, cancer vaccines and oncolytic viruses.

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Emerging therapies for small cell lung cancer

Cited by 297 publications

References 70 publications

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

Shallow whole-genome sequencing of plasma cell-free DNA accurately differentiates small from non-small cell lung carcinoma

<p>Safety and Efficacy of Chemotherapy Combined with Anlotinib Plus Anlotinib Maintenance in Chinese Patients with Advanced/Metastatic Soft Tissue Sarcoma</p>

CAR-T “the living drugs”, immune checkpoint inhibitors, and precision medicine: a new era of cancer therapy

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