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Metastatic triple-negative breast cancer (mTNBC) has the worst prognosis among breast cancer subtypes. Immune checkpoint inhibitors (ICIs) plus chemotherapy have promising survival benefits. Herein, we report a 51-year-old woman whose metastatic lesions were diagnosed as triple-negative subtype and who received tislelizumab plus eribulin treatment and achieved excellent efficacy. To our knowledge, this study is the first attempt to present tislelizumab in combination with eribulin for mTNBC treatment. New treatments resulting in prolonged survival and durable clinical responses would benefit mTNBC patients. Then, we summarize the possible influencing factors of the interaction between tislelizumab and eribulin.

BackgroundBevacizumab has played an important role in the systemic treatment of patients with advanced non-small-cell lung cancer (NSCLC) without gene mutation. In recent years, bevacizumab biosimilar has received marketing approval based on the results of phase III clinical studies. However, more clinical data are needed to verify the efficacy and safety of bevacizumab biosimilar in clinical application.Materials and methodsWe identified 946 patients with locally advanced or metastatic NSCLC who were treated with bevacizumab biosimilar or bevacizumab from January 1, 2019 to November 30, 2021. Comparisons and statistical analyses of bevacizumab biosimilar and bevacizumab were made in terms of efficacy and safety. Efficacy evaluation was performed directly in accordance with RECIST v1.1. Adverse events were graded following the National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.ResultsThe objective response rates (ORRs) were 28.9% in the biosimilar group (n=551) and 30.9% in the reference group (n=395; unstratified ORR risk ratio: 0.934, 95% confidence interval [CI]: 0.677–1.138; unstratified ORR risk difference: −0.020, 95% CI: −0.118–0.035). The estimated median progression-free survival (mPFS) were 6.27 (95% CI: 5.53–7.01) and 4.93 (95% CI: 4.24–5.62) months in the biosimilar and reference groups, respectively (P=0.296). The number of treatment lines, combined treatment regimens and with or without radiotherapy were significant factors affecting the PFS of both groups (P

IntroductionChemotherapy-induced cognitive impairment (CICI), termed “chemobrain”, is highly prevalent in cancer patients following the administration of chemotherapeutic agents. However, the potential pathophysiological mechanisms underlying CICI remain unknown. This study aimed to explore the functional changes of the brain and associated cognitive impairment in non-small cell lung cancer (NSCLC) patients receiving different chemotherapy regimen.MethodsA total of 49 NSCLC patients (25 patients receiving pemetrexed plus carboplatin chemotherapy (PeCC) and 24 patients receiving paclitaxel plus carboplatin chemotherapy (PaCC)) and 61 healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scanning, as well as cognitive function tests including Mini Mental State Exam (MMSE), Montreal Cognitive Assessment (MoCA), Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog). Brain functional activities were measured by regional homogeneity (ReHo) values, which were calculated and compared between groups. In addition, the associations between ReHo values of changed brain regions and scores of cognitive scales were evaluated.ResultsNSCLC patients showed decreased scores of MMSE, MoCA and FACT-Cog and decreased ReHo values in the bilateral superior frontal gyrus (medial), middle frontal gyrus, left inferior frontal gyrus (orbital part) and increased ReHo values in the bilateral insula and caudate. Compared with HCs, patients receiving PeCC demonstrated decreased ReHo values in the right superior frontal gyrus (dorsolateral), left superior frontal gyrus (medial orbital), middle frontal gyrus, insula and rectus gyrus while patients receiving PaCC presented increased ReHo values in the right rolandic operculum, left insula and right caudate. Compared with patients receiving PaCC, patients receiving PeCC had decreased ReHo values in the left superior frontal gyrus (orbital part), middle frontal gyrus and increased ReHo values in the left inferior temporal gyrus, lingual gyrus. Moreover, positive relationships were found between ReHo values of the left and right superior frontal gyrus (medial) and the total scores of FACT-Cog in the patient group.ConclusionThe findings provided evidences that carboplatin-based chemotherapy could cause CICI accompanied by functional changes in the prefrontal cortex, insula, caudate. These might be the pathophysiological basis for CICI of NSCLC patients and were affected by the differences of chemotherapeutic agent administration through different biological mechanisms.

ObjectiveColorectal cancer (CRC) patients that experience early relapse consistently exhibit poor survival. However, no effective approach has been developed for the diagnosis and prognosis prediction of postoperative relapsed CRC.MethodsMultiple datasets from the GEO database and TCGA database were utilized for bioinformatics analysis. WGCNA analyses and RRA analysis were performed to identify key genes. The COX/Lasso regression model was used to construct the recurrence model. Subsequent in vitro experiments further validated the potential role of the hub genes in CRC.ResultsA comprehensive analysis was performed on multiple CRC datasets and a CRC recurrence model was constructed containing LEMD1, SERPINE1, and SIAE. After further validation in two independent databases, we selected LEMD1 for in vitro experiments and found that LEMD1 could regulate CRC cell proliferation, migration, invasion, and promote EMT transition. The Rho-GTPase pulldown experiments further indicated that LEMD1 could affect RhoA activity and regulate cytoskeletal dynamics. Finally, we demonstrated that LEMD1 promoted CRC cell migration through the RhoA/ROCK1 signaling pathway.ConclusionsIn this study, a CRC relapse model consisting of LEMD1, SERPINE1, and SIAE was constructed by comprehensive analysis of multiple CRC datasets. LEMD1 could promote CRC cell migration through the RhoA/ROCK signaling pathway.

Poly ADP ribose polymerases (PARPs) catalyze the modification of acceptor proteins, DNA, or RNA with ADP-ribose, which plays an important role in maintaining genomic stability and regulating signaling pathways. The rapid development of PARP1/2 inhibitors for the treatment of ovarian and breast cancers has advanced research on other PARP family members for the treatment of cancer. This paper reviews the role of PARP family members (except PARP1/2 and tankyrases) in cancer and the underlying regulatory mechanisms, which will establish a molecular basis for the clinical application of PARPs in the future.

BackgroundHER2-positive breast cancer was aggressive, resulting in a poorer prognosis. This multicenter study analyzed the real-world data of women treated with pyrotinib-based therapy, aiming to describe their characteristics, treatment regimens, and to investigate the clinical outcomes.MethodsA total of 141 patients with HER2-positive breast cancer were enrolled from February 2019 to April 2020. Last follow-up time was February 2021. All patients were treated with pyrotinib-based therapy in 21-day cycles. The primary endpoint was progression-free survival (PFS).ResultsThe median PFS (mPFS) for pyrotinib-based therapy was 12.0 months (95%CI 8.1-17.8) in all patients. Among the patients with liver metastases, mPFS was 8.7 months (95%CI, 6.3-15.4) compared to 12.3 months (95%CI, 8.8-23.3) for patients without liver metastases (P=0.172). In addition, patients receiving pyrotinib-based therapy as their >2 lines treatment had a numerically lower mPFS than those receiving pyrotinib-based therapy as their ≤2 lines treatment [8.4 (95%CI, 5.9-15.4) vs. 15.1 (95%CI, 9.3-22.9) months, P=0.107]. The mPFS was 12.2 months (95%CI, 7.9-18.8) in patients with previous exposure to trastuzumab and 11.8 months (95%CI, 6.8-22.9) in patients without previous exposure to trastuzumab (P=0.732). Moreover, mPFS in patients receiving regimens with and without capecitabine were 15.1 months (95%CI, 10.0-18.8) and 8.4 months (95%CI, 6.7-22.9), respectively (P=0.070). Furthermore, in patients with brain metastases, estimated 6-month PFS rate was 70.0%, and rate at 12 months was 60.0%. Seventy patients with measurable lesions were evaluable for response. The objective response rate was 38.6% and disease control rate was 85.7%. The most common adverse event was diarrhea (85.0%).ConclusionPyrotinib-based therapy showed promising efficacy in patients with HER2-positive breast cancer and was well tolerated, especially in patients treated with pyrotinib as ≤2 lines treatment and receiving regimens with capecitabine. The results of this real-world study further confirmed the intriguing efficacy of pyrotinib.

BackgroundAfatinib is approved for first-line treatment of patients with epidermal growth factor receptor mutation-positive (EGFRm+) non-small-cell lung cancer (NSCLC). Here, we report findings from a combined analysis of three phase IIIb studies of afatinib in EGFR tyrosine kinase inhibitor (TKI)-naïve patients.MethodsEGFR-TKI-naïve patients with EGFRm+ NSCLC received afatinib 40 mg/day. Dose reductions were permitted for adverse events (AEs). Efficacy endpoints included progression-free survival (PFS), time to symptomatic progression (TTSP), and tumor response. Subgroup analyses were performed by Eastern Cooperative Oncology Group performance status (ECOG PS), presence of brain metastasis, age and common/uncommon EGFR mutations (plus other factors).Results1108 patients were treated. Median age was 61 years (range, 25–89); 19.2% had baseline brain metastases, 4.4% had ECOG PS ≥2, and 17.9% had tumors harboring uncommon mutations. Treatment-related AEs (TRAEs) were reported in 97.2%, most commonly diarrhea and rash. 41.6% had AEs leading to dose reduction. Median PFS was 13.0 months [95% confidence interval (CI): 12.0–13.8]; median TTSP was 14.8 months (95% CI: 13.9–16.1). Objective response rate (ORR) was 55.0%. Age, presence of baseline brain metastases, major (G719X, L861Q, S768I) or compound uncommon mutations had little/no effect on PFS, TTSP, or ORR, while outcomes were poorer in patients with ECOG PS 2 or exon 20 insertion/T790M mutations.ConclusionsAfatinib was tolerable with no new safety signals. Afatinib demonstrated encouraging efficacy in a broad patient population, including those with brain metastases or uncommon EGFR mutations.

Object: To identify genes of prognostic value which associated with tumor microenvironment (TME) in acute myeloid leukemia (AML).Methods and Materials: Level 3 AML patients gene transcriptome profiles were downloaded from The Cancer Genome Atlas (TCGA) database. Clinical characteristics and survival data were extracted from the Genomic Data Commons (GDC) tool. Then, limma package was utilized for normalization processing. ESTIMATE algorithm was used for calculating immune, stromal and ESTIMATE scores. We examined the distribution of these scores in Cancer and Acute Leukemia Group B (CALGB) cytogenetics risk category. Kaplan-Meier (K-M) curves were used to evaluate the relationship between immune scores, stromal scores, ESTIMATE scores and overall survival. We performed clustering analysis and screened differential expressed genes (DEGs) by using heatmaps, volcano plots and Venn plots. After pathway enrichment analysis and gene set enrichment analysis (GESA), protein-protein interaction (PPI) network was constructed and hub genes were screened. We explore the prognostic value of hub genes by calculating risk scores (RS) and processing survival analysis. Finally, we verified the expression level, association of overall survival and gene interactions of hub genes in the Vizome database.Results: We enrolled 173 AML samples from TCGA database in our study. Higher immune score was associated with higher risk rating in CALGB cytogenetics risk category (P = 0.0396) and worse overall survival outcomes (P = 0.0224). In Venn plots, 827 intersect genes were screened with differential analysis. Functional enrichment clustering analysis revealed a significant association between intersect genes and the immune response. After PPI network, 18 TME-related hub genes were identified. RS was calculated and the survival analysis results revealed that high RS was related with poor overall survival (P < 0.0001). Besides, the survival receiver operating characteristic curve (ROC) showed superior predictive accuracy (area under the curve = 0.725). Finally, the heatmap from Vizome database demonstrated that 18 hub genes showed high expression in patient samples.Conclusion: We identified 18 TME-related genes which significantly associated with overall survival in AML patients from TCGA database.