Prostate cancer is a significant cause of cancer-related deaths in men. Poly (ADP-ribose) polymerase inhibitors (PARPi) have been shown to improve progression-free survival, especially in patients with BRCA1/2 mutations and deficiencies in homologous recombination repair (HRR). We conducted systematic reviews and meta-analyses and found that PARPi, combined with androgen receptor inhibitors, significantly improved overall survival (OS) and progression-free survival (PFS) in BRCA1/2-mutant and HRR-deficient patients. PARPi therapies increased the incidence of adverse events (AEs), including fatigue, nausea, anemia, neutropenia, and thrombocytopenia. Among different PARP inhibitors, Olaparib, Talazoparib, and Rucaparib demonstrated the strongest efficacy in improving OS and PFS but were also linked to higher rates of AEs. Combination therapies with PARPi and hormonal treatments proved more effective than monotherapy, especially in genetically targeted subgroups like BRCA1/2-mutant patients. This umbrella review demonstrates that PARPi treatment significantly improves clinical outcomes, particularly in BRCA1/2-mutant and HRR-deficient mCRPC patients.

Immune checkpoint inhibitors designed to reinvigorate immune responses suppressed by cancer cells have revolutionized cancer therapy. Similarities in immune dysregulation between cancer and infectious diseases have prompted investigations into the role of immune checkpoints in infectious diseases, including the therapeutic potential of immune checkpoint blockade and drug repurposing. While most research has centered around viral infections, data for bacterial infections are emerging. This systematic review reports on the in vivo effect of immune checkpoint blockade on bacterial burden and selected immune responses in preclinical studies of bacterial infection, aiming to assess if there could be a rationale for using immunotherapy for bacterial infections. Of the 42 analyzed studies, immune checkpoint blockade reduced the bacterial burden in 60% of studies, had no effect in 28% and increased the bacterial burden in 12%. Findings suggest that the effect of immune checkpoint blockade on bacterial burden is context-dependent and in part relates to the pathogen. Further preclinical research is required to understand how the therapeutic effect of immune checkpoint blockade is mediated in different bacterial infections, and if immune checkpoint blockade can be used as an adjuvant to conventional infection management strategies.

Microplastics (MPs) are known as substantial environmental and health threats because of their pervasive existence and potential function in human diseases. This study is the first research in which a comprehensive analysis of various impacts of MPs on cancer cells is performed through pharmacological and in silico approaches. Moreover, our results demonstrate that MPs have both promotive and suppressive impacts on cancer cells, changing some of the important features of these kinds of cells including cellular viability, migration, metastasis, and apoptosis. Furthermore, the present study displayed that AP-2 complex subunit mu-1 (AP2M1), Asialoglycoprotein receptor 2 (ASGR2), Bax inhibitor-1 (BI-1), and Ferritin Heavy Chain, and pivotal role in the progression of cancers mediated by MPs. Moreover, our in-silico analysis identified Goserelin, Paclitaxel, Raloxifene, Exemestane, Epirubicin, Trametinib, Vemurafenib, Pactitaxel, and Sorafenib as potential anticancer agents for curing MPS-based cancer. Besides, our results demonstrated that MPs can exacerbate the development of tumor cells by affecting some important mechanisms including oxidative stress, immune suppression, and adjusting of critical signaling pathways. Interestingly, some sorts of MPs also displayed suppressive effects on cancer cells in some particular contexts, highlighting their complicated biological roles in different biological interactions. Ultimately the present survey tries to demonstrate the crucial roles of MPs in cancer cells and the different mechanisms that occur in the mentioned cells in order to emphasize performing more studies about clarifying the roles of MPs in carcinogenesis.

To compare the risk of renal adverse events, particularly acute kidney injury (AKI), between intravitreal anti-vascular endothelial growth factor (anti-VEGF) agents.

We aimed in this study to investigate the relationship between Androgen Deprivation Therapy (ADT) use and the risk of heart failure in patients with prostate cancer. In this research, the negative or positive effects of ADT in the development of cardiovascular diseases or its exacerbation in people with prostate cancer have been investigated.

The first-line treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has recently undergone major changes, and targeted therapies have ushered in a new era of CLL/SLL treatment. Scientists in different countries have successively analyzed the efficacy of various drugs, but safety studies are relatively insufficient. Therefore, this systematic evaluation and retrospective meta-analysis was conducted to compare the differences in adverse effects and their incidence among first-line treatment regimens for CLL/SLL. We searched the Cochrane Library, PubMed, Web of Science, and Embase databases, with a cutoff date of December 2023. Frequency-based network meta-analysis was performed using STATA 16.0, and the risk of bias was assessed using the Cochrane Risk of Bias Assessment Tool (RoB2.0). Thirty-seven randomized controlled trials involving 15,557 patients were included, and the results showed that, compared with other regimens, zanubrutinib had a lower probability of causing adverse hematologic effects and a lower probability of causing severe anemia (SUCRAs: 79. 6%), all-grade anemia (SUCRAs: 87.2%), severe thrombocytopenia (SUCRAs: 97.0%), all-grade thrombocytopenia (SUCRAs: 90.6%), severe neutropenia (SUCRAs: 91.8%) and all-grade neutropenia (SUCRAs: 86.6%) than the other regimens. The higher rates of adverse reactions seen with each of the other first-line regimens were not concentrated in any single regimen. The second-generation BTK inhibitors may have a lower probability of causing hematologic adverse reactions. However, its adverse effects in other systems are still noteworthy. The cardiovascular toxicity of venetoclax combination regimens should not be overlooked.

Diabetic macular edema (DME) is a leading cause of visual impairment and blindness among diabetic patients, its prevalence is continuing to increase worldwide. Faricimab, a bispecific antibody, represents a new generation of treatments for DME.

Chemotherapy, a cornerstone of cancer treatment, is frequently marred by its hepatotoxic effects, which can significantly impede therapeutic efficacy. This systematic review meticulously evaluates the hepatoprotective properties of phytochemicals and plant extracts against chemotherapy-induced liver damage, primarily in experimental animal models. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, an exhaustive search was conducted across databases like SCOPUS, PubMed, and Web of Science, culminating in the inclusion of 61 pertinent studies. These studies illustrate those natural compounds, spanning a diverse array of phytochemicals and plant extracts that can effectively mitigate biochemical markers of liver damage, enhance antioxidant defences, and modulate inflammatory responses in model organisms subjected to hepatotoxic chemotherapeutic agents such as cyclophosphamide, cisplatin, and doxorubicin. Notably, the natural agents reviewed have demonstrated significant reductions in liver enzymes, improved histopathological outcomes, and bolstered cellular antioxidant capacities. The systematic synthesis of data underscores the potential of these natural substances to diminish liver toxicity associated with chemotherapy in preclinical settings. However, the review also highlights critical gaps in research, notably the underreporting of molecular mechanisms and inconsistent data on clinical translatability. To optimize the therapeutic utility of these compounds, future studies should focus on detailed molecular analyses and rigorous clinical trials to validate efficacy and safety, paving the way for integrated approaches in oncological care that minimize hepatic complications.

The development of hypersensitivity reactions (HSRs) to carboplatin can interrupt anticancer treatment and may shorten patient survival. Several studies have evaluated the risk factors for carboplatin HSRs, but the results have been inconclusive.

Poly (ADP-ribose) polymerase inhibitors (PARPis) are effective treatment options for patients with advanced ovarian cancer (OC). A typical adverse event (AE) of these agents is haematological toxicity, which represents the leading cause of treatment modification and discontinuation. This systematic review and meta-analysis aimed to analyse the risk of haematological AEs, including anaemia, neutropenia and thrombocytopenia due to the use of PARPis in patients with OC.

Germ cell tumors (GCTs) are chemosensitive neoplasms with high cure rates; however, a small group of patients present tumors with refractory chemotherapy, with a dismal prognosis and few effective management options. Although immune checkpoint inhibitors (ICIs) are approved for use in chemotherapy refractory GCT, the evidence supporting this indication remains scarce. Original research studies were included on patients with GCTs refractory to chemotherapy treated with ICI up to December 2023. Comprehensive search strategies databases and MeSH keywords were used to locate eligible literature. Study characteristics, participant demographics, and oncological outcomes were recorded. A total of 13 studies (n = 106) were included, five single-patient case reports, one retrospective cohort, six-phase II randomized controlled trials (RCTs), and an abstract from the preliminary results of a phase II RCT. Most of the studies evaluated did not request biomarkers as inclusion criteria. Median overall response rate across studies was 3.4% (range, 0-57) and 0% (range, 0-6) in retrospective cohort and phase II studies. Progressive disease as the best response was present in most patients, with 75% (range, 0-82.9) in the overall population and 82% (range, 75 -83) in the retrospective cohort and phase II trials. Some of the most durable clinical responses documented in this systematic review corresponded to high tumor mutational burden (TMB-H) or high microsatellite instability (MSI-H)/dMMR tumors. Retrospective cohorts and clinical trials evaluating ICIs for the treatment of chemo-refractory GCTs documented limited activity of these drugs as a single intervention in patients not selected by biomarkers, with a tendency to better results described in those with TMB-H or MSI-H/dMMR tumors.

The aim of this network meta-analysis was to clarify the efficacy and safety of different immune checkpoint inhibitors (ICIs) in combination with chemotherapy in the neoadjuvant phase for the treatment of locally advanced esophageal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide. Despite advances in treatment, metastatic colorectal cancer (mCRC) remains a significant challenge due to its heterogeneity and resistance to therapy. Regorafenib, a multikinase inhibitor, can inhibit tumor progression through multiple mechanisms, thereby improving patient prognosis. It has emerged as a potential treatment option for mCRC patients who have progressed on standard therapies. This systematic review and meta-analysis aims to evaluate the efficacy and safety of Regorafenib in this patient population, synthesizing data from clinical trials to provide a comprehensive understanding of its role in mCRC treatment.

The belzutifan is a hypoxia inducible factor-2 alpha (HIF-2α) inhibitor for the treatment of advanced or metastatic clear cell renal cell carcinoma (mccRCC) and has exhibited good safety and efficacy in clinical trials. We conducted a meta-analysis of relevant studies to further clarify the efficacy and safety of belzutifan for the treatment of mccRCC.

Immune-related adverse events (irAE) pose challenges to the use of immune checkpoint inhibitors (ICI). While risk factors for irAE are emerging, most studies are small, retrospective analyses that seldom report on diverse cancers or rare irAE. This paper reports a systematic review that summarises literature on irAE risk factors across cancers and proposes a categorisation approach.

Metastatic colorectal cancer (mCRC) remains a significant cause of mortality despite advancements in treatments. Fruquintinib, a potent VEGFR inhibitor, has shown promise as an advanced therapy for mCRC. This review evaluates the efficacy and safety of fruquintinib compared to placebo in patients with refractory mCRC, focusing on Phase II and III trials.

While in theory antibody drug conjugates (ADCs) deliver high-dose chemotherapy directly to target cells, numerous side effects are observed in clinical practice. We sought to determine the effect of linker design (cleavable versus non-cleavable), drug-to-antibody ratio (DAR), and free payload concentration on systemic toxicity. Two systematic reviews were performed via PubMed search of clinical trials published between January 1998-July 2022. Eligible studies: (1) clinical trial for cancer therapy in adults, (2) ≥ 1 study arm included a single-agent ADC, (3) ADC used was commercially available/FDA-approved. Data was extracted and pooled using generalized linear mixed effects logistic models. 40 clinical trials involving 7,879 patients from 11 ADCs, including 9 ADCs with cleavable linkers (N = 2,985) and 2 with non-cleavable linkers (N = 4,894), were included. Significantly more composite adverse events (AEs) ≥ grade 3 occurred in patients in the cleavable linkers arm (47%) compared with the non-cleavable arm (34%). When adjusted for DAR, for grade ≥ 3 toxicities, non-cleavable linkers remained independently associated with lower toxicity for any AE (p = 0.002). Higher DAR was significantly associated with higher probability of grade ≥ 3 toxicity for any AE. There was also a significant interaction between cleavability status and DAR for any AE (p = 0.002). Finally, higher measured systemic free payload concentrations were significantly associated with higher DARs (p = 0.043). Our results support the hypothesis that ADCs with cleavable linkers result in premature payload release, leading to increased systemic free payload concentrations and associated toxicities. This may help to inform future ADC design and rational clinical application.

PD-1 and PD-L1 inhibitors have emerged as promising therapies for advanced colorectal cancer (CRC), but their efficacy and safety profiles require further evaluation. This meta-analysis aims to assess the efficacy and safety of PD-1/PD-L1 inhibitors in this patient population.

Whether pembrolizumab alone or in combination with chemotherapy is superior to chemotherapy in metastatic cancer remains controversial. The study aims to give the effectiveness and safety of pembrolizumab-related interventions compared to chemotherapy in metastatic cancer.

The combinations of BRAF inhibitor-based targeted therapies with immune checkpoint inhibitors currently represent less common therapeutic approaches in advanced melanoma. The aim of this study was to assess the safety and efficacy of currently available melanoma treatments by conducting a systematic review and network meta-analysis. Four databases were systematically searched for randomized clinical studies that included patients with advanced/metastatic melanoma receiving chemotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitor therapy, or combinations thereof. The primary endpoints were treatment-related adverse events (TRAE), serious adverse events (SAE) of grade ≥ 3 adverse events, therapy discontinuation, progression-free survival (PFS), as well as objective response rate (ORR) and complete response rate (CRR). A total of 63 articles were eligible for our systematic review; 59 of them were included in the statistical analysis. A separate subgroup analysis was conducted to evaluate the efficacy outcomes, specifically in BRAF-positive patients. Triple combination therapy or triple therapy (inhibiting BRAF, MEK and PD1/PDL1 axis) showed significantly longer progression-free survival compared to BRAF + MEK combination therapies (HR = 0.76; 95% CI 0.64-0.9), but similar objective and complete response rates in BRAF-mutated melanoma. This safety analysis suggests that triple therapy is not inferior to combined immune checkpoint inhibitors (ICI) and BRAF/MEK therapies in terms of serious adverse events and therapy discontinuation rates. However, monotherapies and BRAF/MEK combinations showed notable advantage over triple therapy in terms of treatment-related adverse events. Combination strategies including BRAF/MEK-targeted therapies with ICI therapies are effective first-line options for advanced, BRAF-mutant melanoma; however, they are associated with more frequent side effects. Therefore, future RCTs are required to evaluate and identify high-risk subpopulations where triple therapy therapies should be considered.