Insights from molecular dynamics simulations of TRPV1 channel modulators in pain.

TRPV1 is a nonselective cation channel vital for detecting noxious stimuli (heat, acid, capsaicin). Its role in pain makes it a potential drug target for chronic pain management, migraines, and related disorders. This review updates molecular dynamics (MD) simulation studies on the TRPV1 channel, focusing on its gating mechanism, ligand-binding sites, and implications for drug design. The article also explores challenges in developing modulators, SAR optimization, and clinical trial studies. Efforts have been undertaken to concisely present MD simulation findings, with a focus on their relevance to drug discovery.

A new record of the genus Froggattiella Leonardi (Hemiptera, Coccomorpha, Diaspididae) in South Korea.

Background: The genus Froggattiella Leonardi, 1900 belongs to the family Diaspididae, and five species of Froggattiella have been recorded worldwide. In this study, Froggattiellapenicillata (Green, 1905), which attacks bamboos, is newly recorded in South Korea. The colonies of F.penicillata were collected on a bamboo forest located in Gajwa-dong, Jinju-si, Gyeongsangnam-do, South Korea (35.1599, 128.1029). Description of the adult female, host plant, adult female illustrations, and global distribution of this species are provided. New information: Froggattiellapenicillata (Green, 1905) is reported for the first time in South Korea. This species occurrs under sheathing bases of the leaves and is observed attached on the stem and not on the leaf.

miR-429 Suppresses Endometrial Cancer Progression and Drug Resistance via DDX53.

(1) Background: To examine miR-429-meditated DEAD (Asp-Glu-Ala-Asp) box polypeptide 53 (DDX53) function in endometrial cancer (EC). (2) Methods: DDX53 and miR-429 levels were measured using quantitative real-time polymerase chain reaction and western blotting assays, cell invasion and migration using Transwell invasion and wound healing assays, and cell proliferation using colony-forming/proliferation assays. A murine xenograft model was also generated to examine miR-429 and DDX53 functions in vivo. (3) Results: DDX53 overexpression (OE) promoted key cancer phenotypes (proliferation, migration, and invasion) in EC, while in vivo, DDX53 OE hindered tumor growth in the murine xenograft model. Moreover, miR-429 was identified as a novel miRNA-targeting DDX53, which suppressed EC proliferation and invasion. (4) Conclusions: DDX53 and miR-429 regulatory mechanisms could provide novel molecular therapies for EC.

The Role of ROR1 in Chemoresistance and EMT in Endometrial Cancer Cells.

Background and Objectives: Receptor tyrosine kinase-like orphan receptor type 1 (ROR1) plays a critical role in embryogenesis and is overexpressed in many malignant cells. These characteristics allow ROR1 to be a potential new target for cancer treatment. The aim of this study was to investigate the role of ROR1 through in vitro experiments in endometrial cancer cell lines. Materials and Methods: ROR1 expression was identified in endometrial cancer cell lines using Western blot and RT-qPCR. The effects of ROR1 on cell proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) markers were analyzed in two endometrial cancer cell lines (HEC-1 and SNU-539) using either ROR1 silencing or overexpression. Additionally, chemoresistance was examined by identifying MDR1 expression and IC50 level of paclitaxel. Results: The ROR1 protein and mRNA were highly expressed in SNU-539 and HEC-1 cells. High ROR1 expression resulted in a significant increase in cell proliferation, migration, and invasion. It also resulted in a change of EMT markers expression, a decrease in E-cadherin expression, and an increase in Snail expression. Moreover, cells with ROR1 overexpression had a higher IC50 of paclitaxel and significantly increased MDR1 expression. Conclusions: These in vitro experiments showed that ROR1 is responsible for EMT and chemoresistance in endometrial cancer cell lines. Targeting ROR1 can inhibit cancer metastasis and may be a potential treatment method for patients with endometrial cancer who exhibit chemoresistance.

Insulin Receptor Substrate 1 Signaling Inhibits Foxp3 Expression and Suppressive Functions in Treg Cells through the mTORC1 Pathway.

Regulatory T (Treg) cells play an important role in immune homeostasis by inhibiting cells within the innate and adaptive immune systems; therefore, the stability and immunosuppressive function of Treg cells need to be maintained. In this study, we found that the expression of insulin receptor substrate 1 (IRS1) by Treg cells was lower than that by conventional CD4 T cells. IRS1-overexpressing Treg cells showed the downregulated expression of FOXP3, as well as Treg signature markers CD25 and CTLA4. IRS1-overexpressing Treg cells also showed diminished immunosuppressive functions in an in vitro suppression assay. Moreover, IRS1-overexpressing Treg cells were unable to suppress the pathogenic effects of conventional T cells in a transfer-induced colitis model. IRS1 activated the mTORC1 signaling pathway, a negative regulator of Treg cells. Moreover, IRS1 destabilized Treg cells by upregulating the expression of IFN-γ and Glut1. Thus, IRS1 acts as a negative regulator of Treg cells by downregulating the expression of FOXP3 and disrupting stability.

Meta-Analysis of Survival Effects of Receptor Tyrosine Kinase-like Orphan Receptor 1 (ROR1).

Background and Objectives: Identification and targeting of membrane proteins in tumor cells is one of the key steps in the development of cancer drugs. The receptor tyrosine kinase-like orphan receptor (ROR) type 1 is a type-I transmembrane protein expressed in various cancer tissues, which is in contrast to its limited expression in normal tissues. These characteristics make ROR1 a candidate target for cancer treatment. This study aimed to identify the prognostic value of ROR1 expression in cancers. Materials and Methods: We conducted a comprehensive systematic search of electronic databases (PubMed) from their inception to September 2021. The included studies assessed the effect of ROR1 on overall survival (OS) and progression-free survival (PFS). Hazard ratios (HR) from collected data were pooled in a meta-analysis using Revman version 5.4 with generic inverse-variance and random effects modeling. Results: A total of fourteen studies were included in the final analysis. ROR1 was associated with worse OS (HR 1.95, 95% confidence interval (CI) 1.50−2.54; p < 0.001) with heterogeneity. The association between poor OS and ROR1 expression was high in endometrial cancer, followed by ovarian cancer, and diffuse large B cell lymphoma. In addition, ROR1 was associated with poor PFS (HR 1.84, 95% CI 1.60−2.10; p < 0.001), but heterogeneity was not statistically significant. In subgroup analysis, high ROR1 expression showed a significantly higher rate of advanced stage or lymph node metastasis. Conclusions: This meta-analysis provides evidence that ROR1 expression is associated with adverse outcome in cancer survival. This result highlights ROR1 as a target for developmental therapeutics in cancers.

Histone deacetylase 6 plays an important role in TGF-ß-induced murine Treg cell differentiation by regulating cell proliferation.

Regulatory T (Treg) cells maintain immune homeostasis by preventing abnormal or excessive immune responses. Histone deacetylase 6 (HDAC6) regulates expression of Foxp3, and thus, Treg cell differentiation; however, its role in Treg cell differentiation is unclear and somewhat controversial. Here, we investigated the role of HDAC6 in TGF-ß-induced murine Treg cells. HDAC6 expression was higher in Treg cells than in other T helper cell subsets. Pharmacological inhibitors of HDAC6 selectively inhibited Treg cell differentiation and suppressive function. A specific HDAC6 inhibitor induced changes in global gene expression by Treg cells. Of these changes, genes related to cell division were prominently affected. In summary, HDAC6 plays an important role in TGF-ß-induced murine Treg cell differentiation by regulating cell proliferation.

Data collection framework for electronic medical record-based real-world data to evaluate the effectiveness and safety of cancer drugs: a nationwide real-world study of the Korean Cancer Study Group.

Background: Electronic medical records (EMRs) have the highest value among real-world data (RWD). The aim of the present study was to propose a data collection framework of EMR-based RWD to evaluate the effectiveness and safety of cancer drugs by conducting a nationwide real-world study based on the Korean Cancer Study Group. Methods: We considered all patients who received ramucirumab plus paclitaxel (RAM/PTX) for gastric cancer and trastuzumab emtansine (T-DM1) for breast cancer at relevant institutions in South Korea. Standard operating procedures for systematic data collection were prospectively developed. Investigator reliability was evaluated using the concordance rate between the recommended input value for representative fictional cases and the input value of each investigator. Reliability of collected data was evaluated twice during the study period at three institutions randomly selected using the concordance rate between the previously collected data and data collected by an independent investigator. The reliability results of the investigators and collected data were used for revision of the electronic data capture system and site training. Results: Between the starting date of medical insurance coverage and December 2018, a total of 1063 patients at 56 institutions in the RAM/PTX cohort and 824 patients at 60 institutions in the T-DM1 cohort were included. Mean investigator reliability in the RAM/PTX and T-DM1 cohorts was 73.5% and 71.9%, respectively. Mean reliability of collected data in the RAM/PTX and T-DM1 cohort was 90.0% for both cohorts in the first analysis and 89.0% and 84.0% in the second analysis, respectively. Mean missing values of the RAM/PTX and T-DM1 cohorts at the time of simulation of fictional cases and final data analysis decreased from 20.7% to 0.46% and from 18.5% to 0.76%, respectively. Conclusion: This real-world study provides a framework that ensures relevance and reliability of EMR-based RWD for evaluating the effectiveness and safety of cancer drugs.

Estradiol-17 ß levels as a tool for sex determination in Farmed Anguilla japonica.

In this study, the levels of plasma estradiol-17ß (E2) in farmed Anguilla japonica were measured to determine their sex. The analyses were performed for two different size groups (large group, Total length (TL): 61-69 cm; small group, TL: 53-60 cm). The anatomical and histological observations showed that the large group consisted of 29% males and 71% females; the small group, 54% males and 45% females. The gonad histology showed that in the large group, 88% of the eels had immature gonads with ongoing sexual differentiation, 12% were mature with completed sexual differentiation. In the small group, 87% of the eels had immature gonads. The plasma E2 hormone levels were higher in the females of both sizes. In the large group, the average plasma E2 in females was 415 pg/ml, which was significantly higher than the average of 109 pg/ml in males (P < 0.05). In the small group, the average plasma E2 hormone level was 618 pg/ml, which was much higher than the average of 108 pg/ml in males. Quantitative real-time PCR showed that zygote arrest 1 (zar 1) and zona pellucida glycoprotein 3 (zp3) were more highly expressed in females than male. In the H-E staining, an eel in the oil droplet containing ovary stage had a high level of plasma E2 (1500 pg/ml), while an eel with testis in the spermatocyte stage had a low (60 pg/ml). E2 is a potentially useful tool and could play an important role in sex determination in broodstocks.

Laboratory Evaluation of ESGFIBER in Asphalt Paving Mixture.

The global desire to improve the performance of road pavements and move towards a sustainable transportation system has immensely encouraged the usage of fibers in asphalt paving materials. In this study, glass fibers trademarked as ESGFIBER produced by the ESG Industry company Limited from Daejeon, Korea were added in dense-graded asphalt mix. The purpose of this study was to evaluate effects that fibers have on volumetric properties, mechanical properties, and long-term performance of asphalt concrete mixes. ESGFIBER were mixed together with aggregates and asphalt binder in asphalt mix and five different asphalt mixes with different dosage of fibers were evaluated in this study. The Marshall mix design method was used for designing all asphalt mixes, and laboratory tests indirect tensile strength test, deformation strength test and Hamburg wheel tracking test were conducted to evaluate moisture susceptibility, fatigue cracking behavior and rutting resistance of asphalt concrete mixes. The results showed that when ESGFIBER were added in asphalt mix moisture susceptibility, fatigue cracking and rutting resistance were both improved. The usage of ESGFIBER in asphalt concrete mixes can be very beneficial since the mechanical and long-term performance were improved upon the addition of fibers.

Changes in the height of minute tubercles on the skin of Korean bitterling embryos (Acheilognathus signifer) and embryo movement in the host mussels.

Bitterlings are freshwater fish that have developed morphological adaptations to improve the survival of their embryos in host mussels. The most well-known adaptation is the development of minute tubercles, which develop in the early embryonic stage when the embryos have poor swimming ability, and disappear when the embryos reach the free-swimming stage and leave the host mussels. In this study, the embryonic developmental stages of Acheilognathus signifer were analysed to elucidate the relationship between the changes in the height of the minute tubercles and their movement. The height changes in the minute tubercles in the embryos can be divided into five stages, i.e., formation, growth, peak, reduction and disappearance. The authors found that the embryos lived in the gill demibranch of the host mussel until day 6 after hatching. The movement of embryos to the suprabranchial cavity in the gill demibranch was firstly observed on day 7. At this point, the embryos showed a heartbeat and movement. From day 13, the minute tubercles had almost disappeared, and the hatchlings started swimming outside the host mussels from day 16. These observations highlight the different adaptations of minute tubercles among bitterling groups without wing-like projections.

PWWP2B promotes DNA end resection and homologous recombination.

Genome instability is one of the leading causes of gastric cancers. However, the mutational landscape of driver genes in gastric cancer is poorly understood. Here, we investigate somatic mutations in 25 Korean gastric adenocarcinoma patients using whole-exome sequencing and show that PWWP2B is one of the most frequently mutated genes. PWWP2B mutation correlates with lower cancer patient survival. We find that PWWP2B has a role in DNA double-strand break repair. As a nuclear protein, PWWP2B moves to sites of DNA damage through its interaction with UHRF1. Depletion of PWWP2B enhances cellular sensitivity to ionizing radiation (IR) and impairs IR-induced foci formation of RAD51. PWWP2B interacts with MRE11 and participates in homologous recombination via promoting DNA end-resection. Taken together, our data show that PWWP2B facilitates the recruitment of DNA repair machinery to sites of DNA damage and promotes HR-mediated DNA double-strand break repair. Impaired PWWP2B function might thus cause genome instability and promote gastric cancer development.

A Bayesian Network Meta-Analysis of First-Line Treatments for Non-Small Cell Lung Cancer with High Programmed Death Ligand-1 Expression.

We performed a Bayesian network meta-analysis (NMA) to suggest frontline treatments for advanced non-small cell lung cancer (NSCLC) showing high programmed death ligand-1 (PD-L1) expression. A total of 5237 patients from 22 studies were included. In terms of progression-free survival, immune checkpoint inhibitors (ICIs) plus bevacizumab plus chemotherapy had the highest surface under the cumulative ranking curve (SUCRA) value (98.1%), followed by ICI plus chemotherapy (82.9%). In terms of overall survival (OS), dual immunotherapy plus chemotherapy had the highest SUCRA value (79.1%), followed by ICI plus bevacizumab plus chemotherapy (73.4%). However, there was no significant difference in survival outcomes among treatment regimens combined with immunotherapy. Moreover, ICI plus chemotherapy failed to reveal a significant OS superiority to ICI monotherapy (hazard ratio = 0.978, 95% credible internal: 0.771-1.259). In conclusion, this NMA indicates that ICI plus chemotherapy with/without bevacizumab might to be the best options in terms of OS for advanced NSCLC with high PD-L1 expression. However, considering that there was no significant difference in survival outcomes among treatment regimens incorporating immunotherapy and that ICI plus chemotherapy failed to show significant survival benefits over ICI monotherapy, ICI monotherapy may be reasonable as first-line treatment for advanced NSCLC with high PD-L1 expression.

Prognostic value of protein tyrosine kinase 6 overexpression in cancers: a meta-analysis.

BACKGROUND: Protein tyrosine kinase 6 (PTK6) plays an important role in cell proliferation and differentiation. However, the functions of PTK6 appear highly context-dependent and differ depending on the cell type, as well as its intracellular localization. High PTK6 expression in tumor has been associated with poor pathological features and prognosis in some studies, but other studies have reported opposite results. Therefore, we performed this meta-analysis to derive more precise estimations of the association of PTK6 expression with prognosis and clinicopathological features in cancer patients. METHODS: We conducted a literature search in PubMed, Ovid MEDLINE, and MEDLINE databases to cover all articles published until June 2021. All 1475 patients from the eight studies were included in the meta-analysis. Because of heterogeneity in PTK6 expression in non-tumor tissues, the included studies were divided into two subgroups according to PTK expression in non-tumor tissues: the low expression subgroup (LESG) or high expression subgroup (HESG). RESULTS: Patients with high PTK expression showed significantly worse overall survival (OS) in LESG (Hazard Ratio (HR) = 2.53 [95% Confidence Interval (CI), 1.68-3.83], p < 0.0001), but significantly better OS in HESG (HR = 0.56 [95% CI, 0.40-0.78], p = 0.0006). PTK6 expression also showed different associations with clinicopathological features, such as advanced T classification, stage, and differentiation according to PTK6 expression in non-tumor tissues. CONCLUSIONS: PTK6 expression in tumor was a prognostic factor in patients with various cancers, but the direction of prognosis differs, depending on the degree of PTK6 expression in non-tumor tissues.

FGFR4 Gly388Arg Polymorphism Reveals a Poor Prognosis, Especially in Asian Cancer Patients: A Meta-Analysis.

The fibroblast growth factor-4 receptor (FGFR4) is a member of receptor tyrosine kinase. The FGFR4 Gly388Arg polymorphism in the transmembrane domain of the receptor has been shown to increase genetic susceptibility to cancers. However, its prognostic impact in cancer patients still remains controversial. Herein, we performed this meta-analysis to evaluate the clinicopathological and prognostic impacts of the FGFR4 Gly388Arg polymorphism in patients with cancer. We carried out a computerized extensive search using PubMed, Medline, and Ovid Medline databases up to July 2021. From 44 studies, 11,574 patients were included in the current meta-analysis. Regardless of the genetic models, there was no significant correlation of the FGFR4 Gly388Arg polymorphism with disease stage 3/4. In the homozygous model (Arg/Arg vs. Gly/Gly), the Arg/Arg genotype tended to show higher rate of lymph node metastasis compared with the Gly/Gly genotype (odds ratio = 1.21, 95% confidence interval (CI): 0.99-1.49, p = 0.06). Compared to patients with the Arg/Gly or Arg/Arg genotype, those with the Gly/Gly genotype had significantly better overall survival (hazard ratios (HR) = 1.19, 95% CI: 1.05-1.35, p = 0.006) and disease-free survival (HR = 1.25, 95% CI: 1.03-1.53, p = 0.02). In conclusion, this meta-analysis showed that the FGFR4 Gly388Arg polymorphism was significantly associated with worse prognosis in cancer patients. Our results suggest that this polymorphism may be a valuable genetic marker to identify patients at higher risk of recurrence or mortality.

TRK inhibitors block NFKB and induce NRF2 in TRK fusion-positive colon cancer.

Tropomyosin receptor kinase (TRK) fusion is one of the oncogenic driver causes of colon cancer, and tropomyosin 3-neurotrophic receptor tyrosine kinase 1 (TPM3-NTRK1) fusion has been detected in the KM12SM cell line. In the present study, we investigated anticancer mechanisms in the KM12SM cell line using three different form of dovitinib (dovitinib (free base), dovitinib lactate (mono acid), and dovitinib dilactic acid (diacid)) and four TRK inhibitors (LOXO-101, entrectinib, regorafenib, and crizotinib). Exposure of TRK inhibitors at concentrations of 10 nM resulted in the apoptosis of KM12SM cells, whereas regorafenib had no effect. Treatment with all inhibitors except regorafenib also significantly increased the expression levels of the genes nuclear factor-erythroid 2-related factor 2 (NRF2) and glutamyl cysteine ligase catalytic subunit (GCLC) in KM12SM. These drugs significantly reduced expression of the phosphorylated proteins NFκB and COX-2 in the KM12SM cell line, and significantly attenuated KM12SM cell migration, according to a Transwell migration assay. Together, these results suggest that TRK inhibitors block products of carcinogenesis by negatively regulating the NFκB signaling pathway and positively regulating the antioxidant NRF2 signaling pathway.

A Bayesian network meta-analysis on systemic therapy for previously treated gastric cancer.

We conducted a systemic literature review of randomized controlled trials (RCTs) to identify phase III RCTs on salvage treatment of advanced gastric cancer (AGC) and performed a Bayesian network meta-analysis with random-effects model. The overall survival (OS) was the primary outcome of interest. A total of 20 randomized phase III trials were selected. For the second-line treatment, olaparib plus paclitaxel had the highest surface under the cumulative ranking curve value (90.5%), followed by paclitaxel plus ramucirumab (88.4%) and pembrolizumab (86.5%), indicating that these treatments could be the most effective regimens in terms of OS. Nivolumab, chemotherapy, and apatinib showed significant OS benefit compared with best supportive care for the third-line treatment. In conclusion, pembrolizumab may be the most preferable regimen as a second-line treatment for patients with PD-L1-expressing AGC, while paclitaxel-based combinations are recommended for PD-L1-negative AGC. Nivolumab might be the most preferable third-line treatment.

Ramucirumab plus paclitaxel as second-line treatment in patients with advanced gastric or gastroesophageal junction adenocarcinoma: a nationwide real-world outcomes in Korea study (KCSG-ST19-16).

BACKGROUND: Ramucirumab as monotherapy or in combination with paclitaxel is a second-line treatment option recommended for patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma. However, real-world data from large study cohorts focused on ramucirumab plus paclitaxel in gastric cancer are limited. METHODS: The study population comprised all patients with gastric or GEJ cancer who received ramucirumab plus paclitaxel in South Korea between 1 May 2018 and 31 December 2018. We included patients with advanced gastric or GEJ adenocarcinoma and disease progression after first-line platinum and fluoropyrimidine-containing combination chemotherapy. RESULTS: In total, 1063 patients were included in the present study. The objective response rate and disease control rate were 15.1% and 57.7%, respectively. The median progression-free survival was 4.03 months (95% confidence interval, 3.80-4.27) and the median overall survival was 10.03 months (95% confidence interval, 9.33-10.73). Grade 3 or higher treatment-related adverse events with incidence of ⩾5% were neutropenia (35.1%) and anemia (10.5%). Based on multivariable analysis, overall survival was negatively associated with Eastern Cooperative Oncology Group performance status ⩾2, weight loss ⩾10% in the previous 3 months, GEJ of primary tumor, poor or unknown histologic grade, number of metastatic sites ⩾3, presence of peritoneal metastasis, no prior gastrectomy, and time to second-line since first-line treatment <6 months. CONCLUSION: Our large-scale, nationwide, real-world data analysis of an unselected real-world population adds evidence for the efficacy and safety of second-line ramucirumab plus paclitaxel in patients with locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma.

RNF43 and PWWP2B inhibit cancer cell proliferation and are predictive or prognostic biomarker for FDA-approved drugs in patients with advanced gastric cancer.

Background: Abnormal regulation of genes has been closely related to gastric cancer. The characterization of gastric cancer has necessitated the development of new therapeutics as well as the identification of prognostic markers to predict the response to novel drugs. In our study, we used RNA sequencing analyses to show that on gastric cancer tissues to identification of gastric cancer prognostic markers. We specifically chose to study RNF43 because it inhibits gastric cancer-related Wnt/ß-catenin signaling by interacting with Wnt receptors. PWWP2B was chosen because it is a gene which is downregulated in gastric cancer. Methods: Utilizing RNA sequencing analysis, we evaluated the mRNA expression profile in gastric cancer patients. Also, we used HAP1 cells which is a human near-haploid cell line derived from the male chronic myelogenous leukemia cell line KBM-7. These cell line has one copy of each gene, ensuring the edited allele will not be masked by additional alleles. We investigated the screening of 1,449 FDA-approved drugs in HAP1, HAP1 RNF43 KO and HAP1 PWWP2B KO cells. RNA sequencing data reveals that RNF43 and PWWP2B expression were down-regulated in recurrence gastric cancer patients. Next, we investigated the anti-cancer effects of selected drugs in RNF43 and PWWP2B down-regulated MKN45 gastric cancer cells and xenograft model. Results: Among these FDA-approved drugs, three drugs (docetaxel trihydrate, pelitinib and uprosertib) showed strong inhibitory effects in RNF43 KO cells and PWWP2B KO cells. In MKN45 xenograft model, tumor volumes were significantly reduced in the docetaxel trihydrate, uprosertib or pelitinib-treated group. Our data demonstrated that RNF43 and PWWP2B are a biomarker that predict recurrence of gastric cancer. Conclusions: Our findings suggest that docetaxel trihydrate, uprosertib and pelitinib could be used as novel therapeutic agents for the prevention and treatment of gastric cancer with a decrease in RNF43 and PWWP2B expression.

The efficacy and safety of onartuzumab in patients with solid cancers: A meta-analysis of randomized trials.

BACKGROUND: Onartuzumab, a humanized monovalent monoclonal antibody to the MET protein, has been tested in various cancers. We conducted a meta-analysis of randomized phase II and III clinical trials to investigate the efficacy and safety of onartuzumab in solid cancers. METHODS: We searched PubMed, PMC, EMBASE, and the Cochrane library databases. We included randomized phase II or III trials that evaluated the additional benefits of onartuzumab in comparison with the standard treatments. Data on progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were pooled and analyzed. RESULTS: From nine studies, a total of 2,138 patients were included in the meta-analysis. The addition of onartuzumab to the standard treatment resulted in no improvement of PFS (hazard ratio (HR) = 1.00 [95% confidence interval (CI), 0.90-1.11], P = 0.93) and OS (HR = 1.08 [95% CI, 0.94-1.23], P = 0.29). In the subgroup analysis with patients with non-small-cell lung cancer (NSCLC), onartuzumab was not associated with a significant improvement of OS (HR = 1.12 [95% CI, 0.93-1.34], P = 0.23) and PFS (HR = 1.05 [95% CI, 0.91-1.21], P = 0.52). With respect to AEs, onartuzumab increased the incidence of hypoalbuminemia (odds ratio (OR) = 14.8 [95% CI, 3.49-62.71], P < 0.001), peripheral edema (OR = 6.52 [95% CI, 3.60-11.81], P < 0.001), neutropenia (OR = 1.36 [95% CI, 1.03-1.79], P = 0.03), thrombocytopenia (OR = 1.98 [95% CI, 1.03-3.81], P = 0.04), and venous thrombotic events (OR = 3.05 [95% CI, 1.39-6.71], P = 0.006). CONCLUSION: This meta-analysis indicates that the addition of onartuzumab to the standard treatments had no definite survival benefit with increased severe toxicities in patients with solid cancer.