Zhuoqun Lin’s research while affiliated with Zhejiang University and other places

The application of PARP inhibitors has revolutionized cancer treatment and has achieved significant advancements, particularly with regard to tumors with defects in genes involved in homologous recombination repair (HRR) processes, such as BRCA1 and BRCA2. Despite the promising outcomes of PARP inhibitors, certain limitations and challenges still exist, including acquired drug resistance, severe side effects, and limited therapeutic benefits for patients without homologous recombination deficiency (HRD). Various combinations involving PARP inhibitors have been developed to overcome these limitations. Among these, combinations with immune checkpoint inhibitors, antiangiogenic agents, and various small-molecule inhibitors are well-studied strategies that show great potential for optimizing the efficacy of PARP inhibitors, overcoming resistance mechanisms, and expanding target populations. However, the efficiency and overlapping toxicity of these combination strategies for cancers vary among studies, thereby limiting their use. In this review, we describe the mechanisms and limitations of PARP inhibitors to better understand the mechanisms of combination treatments. Furthermore, we have summarized recent studies on the combination of PARP inhibitors with a range of medications and discussed their clinical efficacy. The objective of this review is to enhance the comprehensiveness of information pertaining to this topic.

Introduction Ovarian cancer (OV) is a highly lethal gynecological malignancy with a poor prognosis. Lactate metabolism is crucial for tumor cell survival, proliferation, and immune evasion. Our study aims to investigate the role of lactate metabolism-related genes (LMRGs) in OV and their potential as biomarkers for prognosis, immune microenvironment, and immunotherapy response. Methods Ovarian samples were collected from the TCGA cohort. And 12 lactate-related pathways were identified from the MsigDB database. Differentially expressed genes within these pathways were designated as LMRGs, which undergo unsupervised clustering to identify distinct clusters based on LMRGs. Subsequently, we assessed survival outcomes, immune cell infiltration levels, Hallmaker pathway activation patterns, and chemotaxis among different subtypes. After conducting additional unsupervised clustering based on differentially expressed genes (DEGs), significant differences in the expression of LMRGs between the two clusters were observed. The differentially expressed genes were subjected to subsequent functional enrichment analysis. Furthermore, we construct a model incorporating LMRGs. Subsequently, the lactate score for each tumor sample was calculated based on this model, facilitating the classification of samples into high and low groups according to their respective lactate scores. Distinct groups examined disparities in survival prognosis, copy number variation (CNV), single nucleotide variation (SNV), and immune infiltration. The lactate score served as a quantitative measure of OV's lactate metabolism pattern and an independent prognostic factor. Results This study investigated the potential role of LMRGs in tumor microenvironment diversity and prognosis in OV, suggesting that LMRGs play a crucial role in OV progression and the tumor microenvironment, thus serving as novel indicators for prognosis, immune microenvironment status, and response to immunotherapy.