Cellular senescence is traditionally considered as stable cell cycle arrest state with other phenotypic alterations including the production of an array of cytokines and growth factors. Cancer cells undergo senescence in response to chemotherapeutic agents, radiotherapy and molecular targeted therapy. This form of senescence is termed therapy-induced senescence (TIS) and represents a desirable target in cancer therapy. Recent studies have shown that cellular senescence is a highly heterogeneous and dynamic process. Apart from being cleared by the immune system, the senescent cancer cells may survive for a long time and escape from senescence state. Notably, these cells even have the potential to regain stem-like state with high aggressiveness that eventually facilitates cancer recurrence. Furthermore, the senescence-associated secretory phenotype (SASP) of senescent cells is not always the same, and could establish immunosuppression and a protumor microenvironment. Given these detrimental effects, senescence-inducing chemotherapy followed by senotherapy (the “one–two punch” approach), has emerged. This combined therapy could mitigate unnecessary side effects of the persistent senescent cells, reduce the toxicity of pro-senescence therapy and prolong the survival of cancer patients, and it has a potential future in the precise treatment of cancer. Herein, we review the complex effects of therapy-induced senescence in cancer and highlight the great promise of two-step strategies in anticancer therapies.

Background: Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) that has a poor 5-year overall survival rate due to its lack of precise therapeutic targets. Identifying potential prognostic markers of AITL may provide information regarding the development of precision medicine. Methods: RNA sequence data from PTCL and patient clinic traits were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed gene (DEG) analysis and weighted gene co-expression network analysis (WGCNA) were performed to identify DEGs between the different PTCL subtypes and investigate the relationship underlying co-expression modules and clinic traits. Gene ontology (GO) and protein–protein interaction (PPI) network analyses based on DAVID and the STRING website, respectively, were utilized to deeply excavate hub genes. Results: After removing the outliers from the GSE65823, GSE58445, GSE19069, and GSE6338 datasets using the results from an unsupervised cluster heatmap, 50 AITL samples and 55 anaplastic large cell lymphoma (ALCL) samples were screened. A total of 677 upregulated DEGs and 237 downregulated DEGs were identified in AITL and used to construct a PPI network complex. Using WGCNA, 12 identified co-expression modules were constructed from the 5468 genes with the top 10% of variance, and 192 genes from the Turquoise and Brown modules were with a Gene Significance (GS) cut-off threshold >0.6. Eleven hub genes (CDH1, LAT, LPAR1, CXCL13, CD27, ICAM2, CD3E, CCL19, CTLA-4, CXCR5, and C3) were identified. Only CTLA-4 overexpressed was found to be a poor prognostic factor according to survival analysis. Gene set enrichment analysis (GSEA) identified and validated the intersection of key pathways (T cell receptor, primary immunodeficiency, and chemokine signaling pathways). Conclusion: Our findings provide the framework for the identification of AITL co-expression gene modules and identify key pathways and driving genes that may be novel treatment targets and helpful for the development of a prognostic evaluation index.

Purpose: L-asparaginase or pegaspargase-based chemotherapies have shown promising results in the treatment of extranodal NK/T-cell lymphoma. A retrospective study was conducted to determine the efficacy and safety of pegaspargase, gemcitabine, dexamethasone, and cisplatin (P-GDP) combined chemotherapy in patients with newly diagnosed extranodal NK/T-cell lymphoma. Patients and methods: From September 2013 to November 2016, 57 patients with newly diagnosed, stages I to IV, extranodal NK/T-cell lymphoma received P-GDP chemotherapy. Clinical data from these patients were collected and analyzed to evaluate the efficacy and safety of P-GDP. Results: All patients were subjected to 1–6 cycles of P-GDP chemotherapy, and the median number of cycles of P-GDP regimen administered was 3. The overall response rate was 89.5% (51/57), including a complete response rate of 70.2% (40/59) and a partial response rate of 19.3% (11/57). The median follow-up time was 28 months (range 2–54 months). The 2-year overall survival and progression-free survival (PFS) rates were 82.9% and 75.9%, respectively. For stage I/II patients and stage III/IV patients, 2-year PFS were 80.8% and 66.7%, respectively. The most common grade 3/4 adverse events were neutropenia (42.1%), thrombocytopenia (38.6%), and hypofibrinogenemia (26.3%). No treatment-related deaths were observed. Conclusion: P-GDP combination chemotherapy is highly effective and safe for newly diagnosed patients with extranodal NK/T-cell lymphoma, nasal type. Additional large sample prospective trials are required to confirm these results.