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Cancer Investigation Sep 2023RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered... (Review)
Review
RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.
Topics: Humans; Neoplasms; Drug-Related Side Effects and Adverse Reactions; Hypertension; Neutropenia; Protein Kinase Inhibitors; Lung Neoplasms; Proto-Oncogene Proteins c-ret
PubMed: 37782113
DOI: 10.1080/07357907.2023.2255655 -
Cancers Aug 2023High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6... (Review)
Review
High-risk human papillomavirus (HPV) is etiologically related to cervical cancer, other anogenital cancers and oropharyngeal carcinomas. Low-risk HPV, especially HPV6 and HPV11, cause genital warts and laryngeal papillomas. However, the accumulating data suggests that HPV6 and HPV11 may cause malignant lesions at non-cervical anatomic sites. This review aims to estimate the proportions of single and dual HPV6/11 infections in multiple cancers reported in the last 10 years in the Cochrane, Embasa and PubMed databases. Secondly, the genomes of HPV6/11 were compared with the most common high-risk genotype, HPV16, to determine the similarities and differences. A total of 11 articles were selected, including between one and 334 HPV+ cancer patients. The frequencies of single or dual HPV6/11 infections ranged between 0-5.5% for penile and 0-87.5% for laryngeal cancers and were null for vulvar, vaginal and oral cancers. The genomic similarities between HPV6/11 and HPV16 mainly involved the gene, indicating a limited ability to block cell differentiation. The presence of single or dual HPV6/11 infections in variable proportions of penile and laryngeal cancers support the vaccination strategies that cover these genotypes, not only for preventing genital warts but also for cancer prevention. Other risk factors and co-carcinogens are likely to participate in epithelial carcinogenesis associated with low-risk HPV.
PubMed: 37627099
DOI: 10.3390/cancers15164068 -
Frontiers in Oncology 2024Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations...
BACKGROUND
Early-onset colorectal cancer (CRC), defined as diagnosis before age 50, has increased in recent decades. Although more often diagnosed at advanced stage, associations with other histological and molecular markers that impact prognosis and treatment remain to be clarified. We conducted a systematic review and meta-analysis concerning the prevalence of prognostic and predictive tumor markers for early- vs. late-onset CRC, including oncogene mutations, microsatellite instability (MSI), and emerging markers including immune cells and the consensus molecular subtypes.
METHODS
We systematically searched PubMed for original research articles published between April 2013-January 2024. Included studies compared the prevalence of tumor markers in early- vs. late-onset CRC. A meta-analysis was completed and summary odds ratios (ORs) with 95% confidence intervals (CIs) were obtained from a random effects model via inverse variance weighting. A sensitivity analysis was completed to restrict the meta-analysis to studies that excluded individuals with Lynch syndrome, a hereditary condition that influences the distribution of tumor markers for early-onset CRC.
RESULTS
In total, 149 articles were identified. Tumors from early-onset CRC are less likely to include mutations in (OR, 95% CI: 0.91, 0.85-0.98), (0.63, 0.51-0.78), (0.70, 0.58-0.84), and (0.88, 0.78-1.00) but more likely to include mutations in (1.68, 1.04-2.73) and (1.34, 1.24-1.45). After limiting to studies that excluded Lynch syndrome, the associations between early-onset CRC and (0.77, 0.64-0.92) and mutation (0.81, 0.67-0.97) were attenuated, while an inverse association with mutation was also observed (0.88, 0.78-0.99). Early-onset tumors are less likely to develop along the CpG Island Methylator Phenotype pathway (0.24, 0.10-0.57), but more likely to possess adverse histological features including high tumor grade (1.20, 1.15-1.25), and mucinous (1.22, 1.16-1.27) or signet ring histology (2.32, 2.08-2.57). A positive association with MSI status (1.31, 1.11-1.56) was also identified. Associations with immune markers and the consensus molecular subtypes are inconsistent.
DISCUSSION
A lower prevalence of mutations in and is consistent with extended survival and superior response to targeted therapies for metastatic disease. Conversely, early-onset CRC is associated with aggressive histological subtypes and and mutations, which may serve as therapeutic targets.
PubMed: 38737895
DOI: 10.3389/fonc.2024.1349572 -
Ecotoxicology and Environmental Safety Jan 2024Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to... (Meta-Analysis)
Meta-Analysis Review
Disinfection by-products (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs), have attracted attention due to their carcinogenic properties, leading to varying conclusions. This meta-analysis aimed to evaluate the dose-response relationship and the dose-dependent effect of DBPs on cancer risk. We performed a selective search in PubMed, Web of Science, and Embase databases for articles published up to September 15th, 2023. Our meta-analysis eventually included 25 articles, encompassing 8 cohort studies with 6038,525 participants and 10,668 cases, and 17 case-control studies with 10,847 cases and 20,702 controls. We observed a positive correlation between increased cancer risk and higher concentrations of total trihalomethanes (TTHM) in water, longer exposure durations, and higher cumulative TTHM intake. These associations showed a linear trend, with relative risks (RRs) and 95 % confidence intervals (CIs) being 1.02 (1.01-1.03), 1.04 (1.02-1.06), and 1.02 (1.00-1.03), respectively. Gender-specific analyses revealed slightly U-shaped relationships in both males and females, with males exhibiting higher risks. The threshold dose for TTHM in relation to cancer risk was determined to be 55 µg/L for females and 40 µg/L for males. A linear association was also identified between bladder cancer risk and TTHM exposure, with an RR and 95 % CI of 1.08 (1.05-1.11). Positive linear associations were observed between cancer risk and exposure to chloroform, bromodichloromethane (BDCM), and HAA5, with RRs and 95 % CIs of 1.02 (1.01-1.03), 1.33 (1.18-1.50), and 1.07 (1.03-1.12), respectively. Positive dose-dependent effects were noted for brominated THMs above 35 µg/L and chloroform above 75 µg/L. While heterogeneity was observed in the studies for quantitative synthesis, no publication bias was detected. Exposure to TTHM, chloroform, BDCM, or HAA5 may contribute to carcinogenesis, and the risk of cancer appears to be dose-dependent on DBP exposure levels. A cumulative effect is suggested by the positive correlation between TTHM exposure and cancer risk. Bladder cancer and endocrine-related cancers show dose-dependent and positive associations with TTHM exposure. Males may be more susceptible to TTHM compared to females.
Topics: Male; Female; Humans; Disinfection; Chloroform; Trihalomethanes; Urinary Bladder Neoplasms; Water Pollutants, Chemical; Disinfectants
PubMed: 38183752
DOI: 10.1016/j.ecoenv.2023.115925 -
Chemosphere Oct 2023Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic... (Review)
Review
Glyphosate was classified as a probable human carcinogen (Group 2A) by the International Agency for Research on Cancer (IARC) partially due to strong mechanistic evidence in 2015. Since then, numerous studies of glyphosate and its formulations (GBF) have emerged. These studies can be evaluated for cancer hazard identification with the newly described ten key characteristics (KC) of carcinogens approach. Our objective was to assess all in vivo, ex vivo, and in vitro mechanistic studies of human and experimental animals (mammals) that compared exposure to glyphosate/GBF with low/no exposure counterparts for evidence of the ten KCs. A protocol with our methods adhering to PRISMA guidelines was registered a priori (INPLASY202180045). Two blinded reviewers screened all in vivo, ex vivo, and in vitro studies of glyphosate/GBF exposure in humans/mammals reporting any KC-related outcome available in PubMed before August 2021. Studies that met inclusion criteria underwent data extraction conducted in duplicate for each KC outcome reported along with key aspects of internal/external validity, results, and reference information. These data were used to construct a matrix that was subsequently analyzed in the program R to conduct strength of evidence and quality assessments. Of the 2537 articles screened, 175 articles met inclusion criteria, from which we extracted >50,000 data points related to KC outcomes. Data analysis revealed strong evidence for KC2, KC4, KC5, KC6, KC8, limited evidence for KC1 and KC3, and inadequate evidence for KC7, KC9, and KC10. Notably, our in-depth quality analyses of genotoxicity (KC2) and endocrine disruption (KC8) revealed strong and consistent positive findings. For KC2, we found: 1) studies conducted in humans and human cells provided stronger positive evidence than counterpart animal models; 2) GBF elicited a stronger effect in both human and animal systems when compared to glyphosate alone; and 3) the highest quality studies in humans and human cells consistently revealed strong evidence of genotoxicity. Our analysis of KC8 indicated that glyphosate's ability to modulate hormone levels and estrogen receptor activity is sensitive to both exposure concentration and formulation. The modulations observed provide clear evidence that glyphosate interacts with receptors, alters receptor activation, and modulates the levels and effects of endogenous ligands (including hormones). Our findings strengthen the mechanistic evidence that glyphosate is a probable human carcinogen and provide biological plausibility for previously reported cancer associations in humans, such as non-Hodgkin lymphoma. We identified potential molecular interactions and subsequent key events that were used to generate a probable pathway to lymphomagenesis.
Topics: Animals; Humans; Carcinogens; Herbicides; Neoplasms; Lymphoma, Non-Hodgkin; Mammals; Glyphosate
PubMed: 37474029
DOI: 10.1016/j.chemosphere.2023.139572 -
Molecular Oral Microbiology Aug 2023Squamous cell carcinoma of the oral cavity (OSCC) is the most common head-and-neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of... (Meta-Analysis)
Meta-Analysis Review
Squamous cell carcinoma of the oral cavity (OSCC) is the most common head-and-neck malignancy. Importantly, we are experiencing an alarming rise in the incidence of oropharyngeal squamous cell carcinoma (OPSCC) globally. Oncogenic viruses, human papillomavirus (HPV) and Epstein-Barr virus (EBV), are known to be co-associated with OSCC and OPSCC cases. However, the reported incidence of HPV and EBV co-infection in OSCCs and OPSCCs globally is unknown. To address this, we performed a formal meta-analysis and systematic review on published studies that report the detection of both EBV and HPV in OSCCs and OPSCCs. Our analysis revealed 18 relevant studies out of a total of 1820 cases (1181 from the oral cavity and 639 from the oropharynx). Overall, HPV and EBV co-infection was found in 11.9% of OSCC and OPSCC cases combined (95% CI: 8%-14.1%). Based on anatomical subsite, dual positivity estimates were 10.5% (95% CI: 6.7%-15.1%) for OSCC and 14.2% (95% CI: 9.1%-21.3%) for OPSCC. The highest dual positivity rates described were in European countries: for OSCC 34.7% (95% CI: 25.9%-44.6%) in Sweden and for OPSCC, 23.4% (95% CI: 16.9%-31.5%) in Poland. Given these substantive prevalence rates, the value of detecting dual infection in the diagnosis and prognosis of these cancers deserves careful longitudinal studies, as do implications for cancer prevention and therapy. We further proposed molecular mechanisms that could explain how HPV and EBV could co-contribute to the aetiology of OSCCs and OPSCCs.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Human Papillomavirus Viruses; Papillomavirus Infections; Coinfection; Head and Neck Neoplasms
PubMed: 37014754
DOI: 10.1111/omi.12412 -
Non-coding RNA Sep 2023Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have... (Review)
Review
Head and neck squamous cell carcinomas (HNSCCs) are often diagnosed at advanced stages, incurring significant high mortality and morbidity. Several microRNAs (miRs) have been identified as pivotal players in the onset and advancement of HNSCCs, operating as either oncogenes or tumor suppressors. Distinctive miR patterns identified in tumor samples, as well as in serum, plasma, or saliva, from patients have significant clinical potential for use in the diagnosis and prognosis of HNSCCs and as potential therapeutic targets. The aim of this study was to identify previous systematic reviews with meta-analysis data and clinical trials that showed the most promising miRs in HNSCCs, enclosing them into a biomolecular signature to test the prognostic value on a cohort of HNSCC patients according to The Cancer Genome Atlas (TCGA). Three electronic databases (PubMed, Scopus, and Science Direct) and one registry (the Cochrane Library) were investigated, and a combination of keywords such as "signature microRNA OR miR" AND "HNSCC OR LSCC OR OSCC OR oral cancer" were searched. In total, 15 systematic literature reviews and 76 prognostic clinical reports were identified for the study design and inclusion process. All survival index data were extracted, and the three miRs (miR-21, miR-155, and miR-375) most investigated and presenting the largest number of patients included in the studies were selected in a molecular biosignature. The difference between high and low tissue expression levels of miR-21, miR-155, and miR-375 for OS had an HR = 1.28, with 95% CI: [0.95, 1.72]. In conclusion, the current evidence suggests that miRNAs have potential prognostic value to serve as screening tools for clinical practice in HNSCC follow-up and treatment. Further large-scale cohort studies focusing on these miRNAs are recommended to verify the clinical utility of these markers individually and/or in combination.
PubMed: 37736900
DOI: 10.3390/ncrna9050054 -
International Journal of Molecular... Nov 2023Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample... (Meta-Analysis)
Meta-Analysis Review
Studying primary melanoma and its corresponding metastasis has twofold benefits. Firstly, to better understand tumor biology, and secondly, to determine which sample should be examined in assessing drug targets. This study systematically analyzed all the literature on primary melanoma and its matched metastasis. Following PRISMA guidelines, we searched multiple medical databases for relevant publications from January 2000 to December 2022, assessed the quality of the primary-level studies using the QUIPS tool, and summarized the concordance rate of the most reported genes using the random-effects model. Finally, we evaluated the inter-study heterogeneity using the subgroup analysis. Thirty-one studies investigated the concordance of and in 1220 and 629 patients, respectively. The pooled concordance rate was 89.4% [95% CI: 84.5; 93.5] for and 97.8% [95% CI: 95.8; 99.4] for . When high-quality studies were considered, only mutation status consistency increased. Five studies reported the concordance status of c (93%, 44 patients) and promoter (64%, 53 patients). Lastly, three studies analyzed the concordance of cancer genes involved in the signaling pathways, apoptosis, and proliferation, such as (25%, four patients), (44%, nine patients), and (20%, five patients). Our study found that the concordance of known drug targets (mainly ) during melanoma progression is higher than in previous meta-analyses, likely due to advances in molecular techniques. Furthermore, significant heterogeneity exists in the genes involved in the melanoma genetic makeup; although our results are based on small patient samples, more research is necessary for validation.
Topics: Humans; Melanoma; Skin Neoplasms; Proto-Oncogene Proteins B-raf; Mutation; Melanoma, Cutaneous Malignant
PubMed: 38003476
DOI: 10.3390/ijms242216281 -
Therapeutic Advances in Medical Oncology 2024Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of... (Review)
Review
BACKGROUND
Immunotherapy is an emerging antitumor therapy that can improve the survival of patients with advanced non-small-cell lung cancer (NSCLC). However, only about 20% of NSCLC patients can benefit from this treatment. At present, whether patients with driving gene-positive NSCLC can benefit from immunotherapy is one of the hot issues. Therefore, we conducted a meta-analysis to evaluate the efficacy of immunotherapy in patients with oncogene-driven NSCLC and concluded the efficacy of altered subtypes.
METHODS
A literature search was performed using PubMed, Web of Science, and Cochrane databases. The primary endpoints included the objective response rate (ORR), median progression-free survival (mPFS), and median overall survival (mOS) in patients with oncogene-driven NSCLC.
RESULTS
In all, 86 studies involving 4524 patients with oncogene-driven NSCLC were included in this meta-analysis. The pooled ORRs in clinical trials treated with monoimmunotherapy of EGFR, ALK, and KRAS alteration were 6%, 0%, and 23%, respectively. In retrospective studies, the pooled ORRs of EGFR, ALK, KRAS, BRAF, MET, HER2, RET, and ROS1 alteration were 8%, 3%, 28%, 24%, 23%, 14%, 7%, and 8%, respectively. Among them, the pooled ORRs of KRAS non-G12C mutation, KRAS G12C mutation, BRAF V600E mutation, BRAF non-V600E mutation, MET-exon 14 skipping, and MET-amplification were 33% 40%, 20%, 34%, 17%, and 60%, respectively. In addition, the pooled mPFS rates of EGFR, KRAS, MET, HER2, and RET alteration were 2.77, 3.24, 2.48, 2.31, and 2.68 months, while the pooled mOS rates of EGFR and KRAS alteration were 9.98 and 12.29 months, respectively. In prospective data concerning EGFR mutation, the pooled ORR and mPFS treated with chemo-immunotherapy (IC) reached 38% and 6.20 months, while 58% and 8.48 months with chemo-immunotherapy plus anti-angiogenesis therapy (ICA). Moreover, the pooled mPFS and mOS of monoimmunotherapy was 2.33 months and 12.43 months.
CONCLUSIONS
, and -altered NSCLC patients have poor reactivity to monoimmunotherapy but the efficacy of immune-based combined therapy is significantly improved. G12C mutation, non-V600E mutation, and amplification have better responses to immunotherapy, and more prospective studies are needed for further research.
PubMed: 38420602
DOI: 10.1177/17588359231225036 -
Occupational asbestos exposure and risk of esophageal cancer: A systematic review and meta-analysis.International Journal of Cancer Jun 2024Esophageal cancer (EC), which includes squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), is an important cancer with poor prognosis and high mortality rate.... (Meta-Analysis)
Meta-Analysis
Esophageal cancer (EC), which includes squamous cell carcinoma (ESCC) and adenocarcinoma (EAC), is an important cancer with poor prognosis and high mortality rate. Several occupational exposures have been associated with EC. We aim to investigate the association between occupational asbestos exposure and EC risk, considering types of asbestos and histology of the disease. We included studies mentioned in the list of references in previous reviews and pooled analyses, and we conducted an independent search in PubMed and Scopus. Forest plots of relative risks (RR) were constructed based on the association between occupational asbestos and EC risk. Random-effects models were used to address heterogeneity between 48 independent cohort and case-control studies. We found an association between occupational asbestos exposure and EC (meta-relative risk [RR] = 1.20, 95% confidence interval [CI] = 1.09-1.32; I2 = 58.8%, p-heterogeneity [het] <.001). The results of stratification by job (p-het = .20) indicate an increased RR among asbestos product workers (RR = 1.39, 95% CI = 1.07-1.81), asbestos applicators (RR = 1.41, 95% CI = 1.20-1.67), and construction workers (RR = 1.12, 95% CI = 1.02-1.24). There was no heterogeneity in meta-RR according to outcome (p = .29), geographic region (p = .69), year of publication (p = .59), quality score (p = .73), asbestos type (p = .93), study design (p = .87), and gender (p = .88), control for potential confounders (p = .20), year of first employment (p = .94) and exposure level (p = .43). The stratification analysis by histology type found an increased RR for both ESCC 1.33(1.03-1.71) and EAC 1.45(1.03-2.04) (p-het = .68). We didn't find evidence of publication bias (p = .07). The results of our study suggest that occupational asbestos exposure is associated with an increased risk of EC in both histology types.
Topics: Humans; Occupational Exposure; Asbestos; Esophageal Neoplasms; Adenocarcinoma; Carcinoma, Squamous Cell; Occupational Diseases
PubMed: 38339891
DOI: 10.1002/ijc.34881