OncoBEAM™ is a circulating tumor DNA (ctDNA) test that uses the BEAMing digital PCR technology. We clarified the association between the baseline tumor burden and discordance in the
status by ...metastatic sites in patients with a single metastatic site.
Data from previous Spanish and Japanese studies investigating the concordance of the
status between OncoBEAM™ and tissue biopsy in 221 patients with metastatic colorectal cancer (mCRC) were used. We collected data from patients with liver, peritoneal, or lung metastases and evaluated the concordance rates according to the metastatic site and the association between the concordance rate and tumor burden.
Patients had metastases in the liver (
= 151), peritoneum (
= 25), or lung (
= 45) with concordance rates of 91% (95% confidence interval, 85%-95%), 88% (68%-97%), and 64% (49%-78%), respectively. Factors associated with concordance included the baseline longest diameter and lesion number (
= 0.004), and sample collection interval (
= 0.036). Concordance rates ≥90% were observed in the following groups: liver metastases alone, regardless of the baseline longest diameter and lesion number; peritoneal metastases alone in patients with a baseline longest diameter ≥20 mm; and lung metastases alone in patients with a baseline longest diameter ≥20 mm and/or number of lesions ≥10.
Plasma ctDNA-based liquid biopsy in patients with mCRC may be useful depending on the metastatic site. The maximum diameter and lesion number should be carefully considered when determining patients'
status with only peritoneal or lung metastases.
Many antitumor therapies affect rapidly dividing cells. However, tumor proliferation may be driven by cancer stem cells (CSCs), which divide slowly and are relatively resistant to cytotoxic drugs. ...Thus, many tumors may progress because CSCs are not sensitive to the treatment. In this work, we searched for target genes whose expression is involved in proliferation and chemoresistance of CSCs. Both of these processes could be controlled simultaneously by cell regulators such as microRNAs (miRNAs). Therefore, colonospheres with properties of CSCs were obtained from different colon carcinoma cells, and miRNA profiling was performed. The results showed that miR-451 was downregulated in colonspheres versus parental cells. Surprisingly, expression of miR-451 caused a decrease in self-renewal, tumorigenicity, and chemoresistance to irinotecan of colonspheres. We identified cyclooxygenase-2 (COX-2) as an indirect miR-451 target gene involved in sphere growth. Our results indicate that miR-451 downregulation allows the expression of the direct target gene macrophage migration inhibitory factor, involved in the expression of COX-2. In turn, COX-2 allows Wnt activation, which is essential for CSC growth. Furthermore, miR-451 restoration decreases expression of the ATP-binding cassette drug transporter ABCB1 and results in irinotecan sensitization. These findings correlate well with the lower expression of miR-451 observed in patients who did not respond to irinotecan-based first-line therapy compared with patients who did. Our data suggest that miR-451 is a novel candidate to circumvent recurrence and drug resistance in colorectal cancer and could be used as a marker to predict response to irinotecan in patients with colon carcinoma.
The technical development of high-throughput sequencing technologies and the parallel development of targeted therapies in the last decade have enabled a transition from traditional medicine to ...personalized treatment and care. In this way, by using comprehensive genomic testing, more effective treatments with fewer side effects are provided to each patient-i.e., precision, or personalized, medicine. In several European countries-such as in England, France and Denmark-the governments have adopted national strategies and taken "top-down" decisions to invest in national infrastructure for precision medicine. In other countries-such as Sweden and Germany, with regionally organized healthcare systems-the profession has instead taken "bottom-up" initiatives to build competence networks and infrastructure to enable equal access to precision medicine. In this review, we summarize key learnings at the European level on the implementation process to establish sustainable governance and organization for precision medicine at the regional, national and EU/international levels. We also discuss critical ethical and legal aspects of implementing precision medicine, and the importance of access to real-world data and performing clinical trials for evidence generation, as well as the need for improved reimbursement models, increased cross-disciplinary education and patient involvement. In summary, precision medicine represents a paradigm shift, and modernization of healthcare and all relevant stakeholders-i.e., healthcare, academia, policy makers, industry, and patients-must be involved in this system transformation, to create a sustainable, non-siloed ecosystem for precision healthcare that benefits our patients and society at large. This article is protected by copyright. All rights reserved.
The connection between heart failure (HF) and cancer through multiple pathways such as inflammation, oxidative stress, and neurohormonal activation, among others, is well established. As a ...consequence, increases in plasma levels of several biomarkers have been described in both disorders. The most consistent information is related to natriuretic peptides (NPs). Although they are known to be produced in the ventricles as a response to myocardial distension, and thus can be useful for the diagnosis and prognosis of HF, and also for the management of chemotherapy-induced myocardial damage, they are also produced by tumour cells. In this regard, increased plasma levels of NPs have been described in patients with multiple malignancies in the absence of volume overload. Natriuretic peptide levels have been shown to correlate directly with the extension of tumours and with poorer outcomes. Moreover, some data indicate that they may help in the detection of subclinical tumours. Given that these peptides have been described to have anti-proliferative and anti-angiogenic effects, a plausible hypothesis is that they may be produced by tumours as a negative feed-back mechanism to avoid tumour progression. This would lead to increased levels of NPs in plasma that could be potentially useful for early detection of malignancies as well as for a prognostic assessment. Nevertheless, since the sample size of many studies published so far is limited, more data are needed to provide consistent data in order to confirm or rule out this hypothesis.
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•There are several connections between HF and cancer. Natriuretic peptides (NPs) may play a significant role.•Patients with HF may have enhanced plasma levels of cancer markers that correlate directly with those of NT-proBNP.•NPs levels have been shown to correlate with the extension of tumours and with poor outcomes.•NPs have antiproliferative and anti-angiogenic effects. This has been demonstrated both in in vitro and in vivo experiments.•NT-proBNP is an independent predictor of the development of cancer.
Abstract
Background
Adoption of high-throughput, gene panel-based, next-generation sequencing (NGS) into routine cancer care is widely supported, but hampered by concerns about cost. To inform ...policies regarding genomic testing strategies, we propose a simple metric, cost per correctly identified patient (CCIP), that compares sequential single-gene testing (SGT) vs. multiplex NGS in different tumor types.
Materials and Methods
A genomic testing cost calculator was developed based on clinically actionable genomic alterations identified in the European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets. Using sensitivity/specificity data for SGTs (immunohistochemistry, polymerase chain reaction, and fluorescence in situ hybridization) and NGS and marker prevalence, the number needed to predict metric was monetarized to estimate CCIP.
Results
At base case, CCIP was lower with NGS than sequential SGT for advanced/metastatic non-squamous non-small cell lung cancer (NSCLC), breast, colorectal, gastric cancers, and cholangiocarcinoma. CCIP with NGS was also favorable for squamous NSCLC, pancreatic, and hepatic cancers, but with overlapping confidence intervals. CCIP favored SGT for prostate cancer. Alternate scenarios using different price estimates for each test showed similar trends, but with incremental changes in the magnitude of difference between NGS and SGT, depending on price estimates for each test.
Conclusions
The cost to correctly identify clinically actionable genomic alterations was lower for NGS than sequential SGT in most cancer types evaluated. Decreasing price estimates for NGS and the rapid expansion of targeted therapies and accompanying biomarkers are anticipated to further support NGS as a preferred diagnostic standard for precision oncology.
Adoption of next-generation sequencing (NGS) into routine cancer care is widely supported, but hampered by cost concerns. This article reports a simple metric to inform policies on genomic testing strategies: cost per correctly identified patient.
Background
Caveolin-1 (CAV-1), the main scaffold protein in caveolae, is frequently deregulated in human cancer. Of importance, this protein has been described to show tumor suppressor or oncogenic ...properties depending on the cell type and the stage of the disease. In fact, its role in colorectal cancer (CRC) remains to be fully clarified due to discrepancies in the literature.
Methods
We analyzed CAV-1 by western blot in a set of early-stage CRC patients with paired tumor tissue and normal colonic mucosa available. CAV-1 mRNA and expression levels of miR-124, 133 and 802 were quantified by real-time PCR.
Results
We found CAV-1 strongly downregulated in 76.2% of tumor samples and associated with the subgroup of elderly patients (
p
= 0.027). We observed by real-time PCR a lack of correlation between CAV-1 mRNA and protein levels in some cases with CAV-1 downregulated by western blot, and miR-124 deregulation was identified as a potential contributing alteration to decrease CAV-1 protein expression.
Conclusion
CAV-1 is commonly downregulated in patients with primary CRC, which suggests its tumor suppressor role in early stages of this disease. Moreover, based on our findings, the previous discrepancies observed in different studies to date could be due to a complex posttranscriptional
CAV
-1 regulation.
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