Background: Pyrotinib, an irreversible pan-ERBB inhibitor, has shown promising antitumour activity, and acceptable tolerability. This research was conducted to evaluate the actual use and effectiveness of pyrotinib in China, therefore, contributed to solve the problem of real-world data scarcity. Methods: In this retrospective study, 168 patients who received pyrotinib treatment for HER2-positive metastatic breast cancer (MBC) in Hunan Province from June Chen et al.

Purpose: Patients with HER2-positive (HER2+) metastatic breast cancer (MBC) have poor prognoses. Pyrotinib has shown promising antitumor activity in MBC patients to improve progression-free survival (PFS). However, findings based on real-world data to analyze whether pyrotinib affects overall survival (OS) remain scarce. Experimental design:This real-world study is an exploratory analysis of brain metastasis (BM) and the final update of our preceding study of 168 patients with HER2+ MBC. PFS, OS, tumor mutation burden (TMB), clinical benefit rate (CBR) and overall response rate (ORR) were analyzed.Results: Pyrotinib treatment led to a median PFS time of 8.00 months and a median OS of 19.07 months in the 168 participants. High TMB was associated with poor OS (P = 0.0072) and PFS (P = 0.0028). In the 39 patients with BM, the median PFS and OS were 8.67 and 13.93 months, respectively. The surgery/radiation (S/R) group of patients with BM had prolonged survival (PFS: 9.97 vs. 7.73 months P = 0.19; OS: 20.67 vs. 12.43 months P = 0.021) compared with the no surgery/no radiation group (NS/NR). The CBR was 58.6% (S/R) vs. 41.4% (NS/NR), while the ORR was 24.1% (S/R) vs. 31.0% (NS/NR). Conclusion:Pyrotinib shows promise as a novel pan-HER2 tyrosine kinase inhibitor (TKI) for the treatment of BM and should be evaluated further. Surgical or radiotherapy in combination with pyrotinib was found to statistically improve OS in our cohort. TMB could be an exploratory biomarker for predicting PFS and OS, but its clinical application still needs further verification.

Background and Objective: Previous studies have demonstrated that the oncogene trophoblast cell surface antigen 2 (TROP2) has great application prospects as a therapeutic target. However, few literature reviews have systematically summarized and evaluated its role in cancer therapy. This study aims to summarize the molecular structure, functions, signal transduction pathways, and prognostic value of TROP2, and explore therapeutic agents that target TROP2. Methods: A total of 1,376 published literatures from PubMed and 614 published literatures from EMBASE were retrieved by searching "TROP2" or "Trophoblast cell surface antigen 2". The search was conducted on December 12, 2020, and updated on November 20, 2022. The cBioportal and GEPIA (Gene Expression Profiling Interactive Analysis) databases were used to analyze the expression, mutation, and prognostic value of TROP2 in different types of cancer. Key Content and Findings: TROP2 is overexpressed in different tumor tissues and plays roles in cell proliferation, invasion, migration, apoptosis, and treatment resistance by binding to or interacting with several molecules. As a therapeutic target, TROP2 is particularly suitable for antibody-based therapies.Monoclonal antibodies, bispecific antibodies, antibody-drug conjugates (ADCs), virus-like particles, and antibody drugs in combination with traditional chemotherapy, immunotherapy, radioimmunotherapy, photoimmunotherapy, and nanoparticles that target TROP2 have thus far been rapidly developed. For example, sacituzumab govitecan (IMMU-132), a TROP2-targeting ADC, was granted accelerated approval for the treatment of metastatic triple-negative breast cancer (TNBC). Anti-TROP2 antibody-conjugated nanoparticles (ST-NPs) are a promising vehicle for delivering doxorubicin in targeted TNBC therapy. Conclusions:The availability of TROP2-targeting ADCs makes TROP2 an accessible and promising therapeutic target for advanced metastatic cancers. The present review describes the important role of TROP2 in tumorigenesis and its potential applications as a promising biomarker and therapeutic target that is capable of reversing resistance.