The evolving landscape of immunotherapy in small-cell lung cancer: A focus on predictive biomarkers

Gelsomino, Francesco; Parisi, Claudia; Casolari, Laura; Melotti, Barbara; Sperandi, Francesca; Ardizzoni, Andrea

doi:10.1016/j.ctrv.2019.08.003

Cited by 48 publications

(47 citation statements)

References 67 publications

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“…To further extend these findings, we analyzed cells derived from another notoriously chemoresistant tumor, non-small cell lung cancer (NSCLC). We incubated human H1299 lung cancer cells with L-OHP, because platinum compounds are a standard therapy for lung tumors (Foy et al 2017;Gelsomino et al 2019). In accordance with the data obtained in renal cancer cell lines, three structurally different HDACi (VPA, MS-275, LBH-589) promoted antiproliferative effects of L-OHP against H1299 cells ( Fig.…”

Section: Hdac Inhibition Does Not Promote Chemoresistancesupporting

confidence: 72%

Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes

Kiweler

Wünsch

Wirth

et al. 2020

J Cancer Res Clin Oncol

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Purpose We set out to determine whether clinically tested epigenetic drugs against class I histone deacetylases (HDACs) affect hallmarks of the metastatic process. Methods We treated permanent and primary renal, lung, and breast cancer cells with the class I histone deacetylase inhibitors (HDACi) entinostat (MS-275) and valproic acid (VPA), the replicative stress inducer hydroxyurea (HU), the DNA-damaging agent cis-platinum (L-OHP), and the cytokine transforming growth factor-β (TGFβ). We used proteomics, quantitative PCR, immunoblot, single cell DNA damage assays, and flow cytometry to analyze cell fate after drug exposure. Results We show that HDACi interfere with DNA repair protein expression and trigger DNA damage and apoptosis alone and in combination with established chemotherapeutics. Furthermore, HDACi disrupt the balance of cell adhesion protein expression and abrogate TGFβ-induced cellular plasticity of transformed cells. Conclusion HDACi suppress the epithelial-mesenchymal transition (EMT) and compromise the DNA integrity of cancer cells. These data encourage further testing of HDACi against tumor cells.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Section: Hdac Inhibition Does Not Promote Chemoresistancesupporting

confidence: 72%

Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes

Kiweler

Wünsch

Wirth

et al. 2020

J Cancer Res Clin Oncol

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“…15,16 PD-L1 expression and tumor mutational burden have been also suggested as predictive biomarkers of response to immunotherapy for patients with SCLC. 17 It is however interesting to note that immunohistochemical staining of neuroendocrine bladder tumor including SCCB has shown less expression of PD-L1 and density of CD8 + T lymphocyte infiltration. 18 In our case, we also performed immunohistochemical staining of specimens resected by TURBT.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of recurrent small cell carcinoma of urinary bladder with pembrolizumab

et al. 2020

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Abbreviations & Acronyms CT = computed tomography ICI = immune checkpoint inhibitor LRC = laparoscopic radical cystectomy MRI = magnetic resonance imaging NAC = neoadjuvant chemotherapy NSE = neuron specific enolase ORR = overall response rate PD-1 = programmed death 1 PD-L1 = programmed death ligand 1 SCCB = small cell carcinoma of urinary bladder SCLC = small cell lung cancer TURBT = transurethral resection of bladder tumor UC = urothelial carcinoma

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“…Immune-related adverse events (irAEs) were reported in 39.9% of patients in the atezolizumab arm, compared to 24.5% in the placebo arm, and the most common were rash (any grade 18.7%) and hypothyroidism (any grade 12.6%). Although the benefit was minimal and is likely limited to a subset of patients, which, to date, cannot be identified [68], this is the first strategy to improve ES-SCLC survival in decades, so that the combination of chemotherapy and atezolizumab has been approved by the Food and Drug Administration (FDA) in first-line treatment of SCLC.…”

Section: Sclc First Line and Maintenancementioning

confidence: 99%

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

Maggio

Manuzzi

Ricci

et al. 2020

Cancers

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Background: Neuroendocrine neoplasms are rare entities consisting of a heterogeneous group of tumors that can originate from neuroendocrine cells present in the whole body. Their different behavior, metastatic potential, and prognosis are highly variable, depending on site of origin, grade of differentiation, and proliferative index. The aim of our work is to summarize the current knowledge of immunotherapy in different neuroendocrine neoplasms and its implication in clinical practice. Results: Several studies evaluated the efficacy and safety of immunotherapy in neuroendocrine neoplasms, in any setting of treatment, alone or in combination. Studies led to approval in neuroendocrine neoplasia of the lung, in combination with chemotherapy as first-line treatment or as a single-agent in a third-line setting, and Merkel cell carcinoma as a single agent. Results in other settings have been disappointing so far. Conclusions: Immunotherapy seems a valid treatment option for high grade, poorly differentiated neoplasms. Future trials should explore the combination of immunotherapy with other agents, such as anti-angiogenic or other immunotherapy agents, in order to evaluate potential efficacy in low and intermediate grades, well differentiated tumors.

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The evolving landscape of immunotherapy in small-cell lung cancer: A focus on predictive biomarkers

Cited by 48 publications

References 67 publications

Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes

Histone deacetylase inhibitors dysregulate DNA repair proteins and antagonize metastasis-associated processes

Successful treatment of recurrent small cell carcinoma of urinary bladder with pembrolizumab

Landscape and Future Perspectives of Immunotherapy in Neuroendocrine Neoplasia

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