scholarly journals Pharmacogenomics, Pharmacokinetics and Circulating Proteins As Biomarkers for Bevacizumab Treatment Optimization in Patients with Cancer: A Review

2020 ◽  
Vol 10 (3) ◽  
pp. 79 ◽  
Author(s):  
Apostolos Papachristos ◽  
Gregory B. Sivolapenko

Bevacizumab is a monoclonal antibody that targets VEGF-A and inhibits tumor angiogenesis. Bevacizumab is approved for the treatment of various cancer, including metastatic colorectal cancer (mCRC), ovarian cancer, lung cancer, and others. Thus, it is widely used in oncology, but contrary to other therapeutic classes, there is still a lack of validating predictive factors for treatment outcomes with these agents. In recent years, the research for factors predictive of anti-VEGF treatments and especially bevacizumab response has been one of the most competitive translational research fields. Herein, we review and present the available literature of the clinical use of biomarkers, pharmacogenomics (PG), and therapeutic drug monitoring (TDM) approaches that can be used for the optimization of bevacizumab use in the era of precision medicine.

1989 ◽  
Vol 82 (7) ◽  
pp. 388-390 ◽  
Author(s):  
J J T Tate ◽  
J Northway ◽  
G T Royle ◽  
I Taylor

A new type of faecal occult blood test, EZ-Detect™, has been evaluated in 404 patients presenting with symptoms suggestive of colorectal disease. The test avoids handling of stools and gives a result which patients can read themselves - factors which may increase patient compliance. In comparison with the Haemoccult™ test, EZ-Detect has the same sensiti-vity for blood in laboratory conditions. In clinical use 98% of patients expressed a preference for EZ-Detect but it detected significantly fewer patients with cancer than did Haemoccult (P = < 0.05). In its present form, this type of test would be unsuitable for population screening for colorectal cancer even if improved compliance is achieved.


2020 ◽  
Vol 27 (4) ◽  
pp. 309-312
Author(s):  
Lucian Sorin ANDREI ◽  
Radu Sorin POPISTEANU ◽  
Adriana ANDREI ◽  
Alexandru MICU ◽  
Ioana DINU

Bevacizumab is a monoclonal antibody which has shown promising results in the treatment of varied malignant pathology, including metastasized colorectal cancer. It acts by inhibiting VEGF (vascular endothelial growth factor), and one of its most cited complications is intestinal perforation, by mechanisms which are not yet fully understood. We present the case of a 68 year old patient, operated for metastasized colorectal cancer, which underwent chemotherapy with Bevacizumab, and shortly after initiating therapy developed fi stula of low colorectal anastomosis, followed by ischemic perforation of the small intestine.


2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A24-A24
Author(s):  
Christina Jensen ◽  
Jeppe Thorlacius-Ussing ◽  
Patryk Drobinski ◽  
Morten Karsdal ◽  
Anne-Christine Bay-Jensen ◽  
...  

BackgroundAutoantibodies are classically associated with autoimmune diseases but have recently emerged as attractive cancer biomarkers as they can be easily assessed in serum. Certain autoantibodies have been shown to promote cancer while others contribute to the body’s defense against it. Cancer progression is associated with excessive remodeling of the extracellular matrix (ECM) and collagen, but little is known about the role of autoantibodies against collagen in cancer. To investigate autoreactivity against collagen in cancer, we developed a novel biomarker assay to quantify autoantibodies against type III collagen products in serum from patients with various solid tumor types and compared levels with those find in healthy controls.MethodsThe presence and levels of autoantibodies against denatured type III collagen were measured in pretreatment serum from 223 patients with bladder cancer (n=20), breast cancer (n=20), colorectal cancer (n=20), head and neck cancer (n=20), kidney cancer (n=20), liver cancer (n=3), lung cancer (n=20), melanoma (n=20), ovarian cancer (n=20), pancreatic cancer (n=20), prostate cancer (n=20), and stomach cancer (n=20), and compared to age-matched healthy controls (n=33). Statistical differences were analyzed using the Kruskal-Wallis test adjusted for Dunn’s multiple comparisons test.ResultsSerum levels of autoantibodies against type III collagen were significantly lower in patients with bladder cancer (p=0.0007), breast cancer (p=0.0002), colorectal cancer (p<0.0001), head and neck cancer (p=0.0005), kidney cancer (p=0.005), liver cancer (p=0.030), lung cancer (p=0.0004), melanoma (p<0.0001), ovarian cancer (p<0.0001), pancreatic cancer (p<0.0001), prostate cancer (p<0.0001), and stomach cancer (p<0.0001) compared to healthy controls. This autoimmunity biomarker could discriminate between cancer and healthy controls with an AUROC value of 0.88 (p<0.0001).ConclusionsIn this study, we observed that cancer patients with different solid tumor types have downregulated levels of circulating autoantibodies directed against type III collagen compared to healthy controls suggesting that autoantibodies against type III collagen and tumor fibrosis may be important for tumor control and eradication. This autoimmunity biomarker may have the potential for studying and monitoring the close relationship between autoimmunity and cancer such as the risk of developing cancer on rheumatoid arthritis immunosuppressant or the risk of developing immune-related adverse events on cancer immunotherapy.Ethics ApprovalThe serum samples in this study were obtained from the commercial vendor Proteogenex and BioIVT, and according to the vendors, sample collection was approved by an Institutional Review Board or Independent Ethical Committee and patients gave their informed consent (Protocol numbers PG-ONC 2003/1 and WIRB® Protocol #20161665). All investigations were carried out according to the Helsinki Declaration.


2019 ◽  
Vol 18 (5) ◽  
pp. 18-28
Author(s):  
G. G. Khakimova ◽  
Zh. R. Cherkasova ◽  
S. A. Tsurkan ◽  
G. A. Fedchikov ◽  
N. V. Suganov ◽  
...  

The objective of the study was to assess the feasibility of using CA -62 marker of epithelial carcinomas for monitoring treatment response and detecting cancer progression or recurrence during chemotherapy.Material and Methods. A 12-month double-blind clinical trial was conducted by two independent groups: clinical oncologists and biochemists, and involved 89 patients with different cancers confirmed by histopathological findings. The other inclusion criteria were: the presence of at least one measurable lesion according to the RECIST criteria, ECOG performance status 0-2 and satisfactory laboratory parameters. The expression of CA -62 cancer marker was measured by immunochemiluminescent assay used for the detection of epithelial carcinomas.Results. The elevated level of CA -62 marker was observed in 76 patients before starting the treatment. After completion chemotherapy, the level of this marker decreased to the normal reference ranges (<4600 U/ml) in 53 % of patients and remained increased in 24 % of patients. Of 24 % of patients with the initial low level of CA -62 marker (1000–4000 U/ml) before treatment, 12 % had no changes in the level of this marker during chemotherapy; however, 5 % of these patients had disease progression and 7 % had stable disease after starting the treatment. In 12 % of patients with an initial low CA -62 level, it increased during chemotherapy, indicating disease progression.Conclusion. The changes in the level of CA -62 marker during chemotherapy in patients with gastric cancer, small-cell lung cancer, colorectal cancer, neuroendocrine cancer and ovarian cancer showed a high correlation (76–100 % depending on the tumor site) with the performance status of the patients according to RECIST criteria. The CA -62 marker was shown to be feasible for monitoring gastric cancer, small-cell lung cancer, colorectal cancer, neuroendocrine cancer and ovarian cancer as well as for assessing the response to chemotherapy.


2009 ◽  
Vol 27 (13) ◽  
pp. 2217-2224 ◽  
Author(s):  
Kristine H. Allin ◽  
Stig E. Bojesen ◽  
Børge G. Nordestgaard

Purpose We tested the hypothesis that baseline plasma levels of C-reactive protein (CRP) are associated with risk of incident cancer in the general population and early death in patients with cancer. Patients and Methods A total of 10,408 individuals from the Danish general population who had CRP measured at baseline were observed for up to 16 years; 1,624 developed cancer, and of these, 998 patients died during follow-up. Follow-up was 100% complete. We excluded individuals with a cancer diagnosis at baseline. Results Baseline CRP levels more than 3 versus less than 1 mg/L were associated with multifactorially adjusted hazard ratios of 1.3 (95% CI, 1.0 to 1.6) for cancer of any type, 2.2 (95% CI, 1.0 to 4.6) for lung cancer, 1.9 (95% CI, 0.8 to 4.6) for colorectal cancer, and 0.7 (95% CI, 0.4 to 1.4) for breast cancer. Corresponding hazard ratios for the highest versus the lowest quintile of baseline CRP levels were 1.3 (95% CI, 1.0 to 1.6), 2.1 (95% CI, 1.2 to 3.8), 1.7 (95% CI, 0.8 to 3.2), and 0.9 (95% CI, 0.5 to 1.7), respectively. Multifactorially adjusted hazard ratios for early death in patients with cancer were 1.8 (95% CI, 1.2 to 2.7) for CRP more than 3 versus less than 1 mg/L and 1.4 (95% CI, 1.1 to 1.7) for the highest versus the lowest quintile. Elevated CRP levels were associated with early death in patients with cancer having localized disease, but not in those with metastases (interaction; P = .03). Conclusion Elevated levels of CRP in cancer-free individuals are associated with increased risk of cancer of any type, of lung cancer, and possibly of colorectal cancer. Moreover, elevated levels of baseline CRP associate with early death after a diagnosis of any cancer, particularly in patients without metastases.


1994 ◽  
Vol 5 (4) ◽  
pp. 375-376 ◽  
Author(s):  
J. Verweij ◽  
J. Wanders ◽  
A.L. Nielsen ◽  
N. Pavlidis ◽  
F. Calabresi ◽  
...  

2020 ◽  
Vol 4 (5) ◽  
pp. 805-812
Author(s):  
Riska Chairunisa ◽  
Adiwijaya ◽  
Widi Astuti

Cancer is one of the deadliest diseases in the world with a mortality rate of 57,3% in 2018 in Asia. Therefore, early diagnosis is needed to avoid an increase in mortality caused by cancer. As machine learning develops, cancer gene data can be processed using microarrays for early detection of cancer outbreaks. But the problem that microarray has is the number of attributes that are so numerous that it is necessary to do dimensional reduction. To overcome these problems, this study used dimensions reduction Discrete Wavelet Transform (DWT) with Classification and Regression Tree (CART) and Random Forest (RF) as classification method. The purpose of using these two classification methods is to find out which classification method produces the best performance when combined with the DWT dimension reduction. This research use five microarray data, namely Colon Tumors, Breast Cancer, Lung Cancer, Prostate Tumors and Ovarian Cancer from Kent-Ridge Biomedical Dataset. The best accuracy obtained in this study for breast cancer data were 76,92% with CART-DWT, Colon Tumors 90,1% with RF-DWT, lung cancer 100% with RF-DWT, prostate tumors 95,49% with RF-DWT, and ovarian cancer 100% with RF-DWT. From these results it can be concluded that RF-DWT is better than CART-DWT.  


2014 ◽  
Vol 146 (5) ◽  
pp. S-408
Author(s):  
Yezaz A. Ghouri ◽  
Sachin Batra ◽  
Nirav C. Thosani ◽  
Sushovan Guha

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 918
Author(s):  
Heejin Lee ◽  
Oh-Bin Kwon ◽  
Jae-Eon Lee ◽  
Yong-Hyun Jeon ◽  
Dong-Seok Lee ◽  
...  

The overall five-year survival rate for late-stage patients of ovarian cancer is below 29% due to disease recurrence and drug resistance. Cancer stem cells (CSCs) are known as a major contributor to drug resistance and recurrence. Accordingly, therapies targeting ovarian CSCs are needed to overcome the limitations of present treatments. This study evaluated the effect of trimebutine maleate (TM) targeting ovarian CSCs, using A2780-SP cells acquired by a sphere culture of A2780 epithelial ovarian cancer cells. TM is indicated as a gastrointestinal motility modulator and is known to as a peripheral opioid receptor agonist and a blocker for various channels. The GI50 of TM was approximately 0.4 µM in A2780-SP cells but over 100 µM in A2780 cells, demonstrating CSCs specific growth inhibition. TM induced G0/G1 arrest and increased the AV+/PI+ dead cell population in the A2780-SP samples. Furthermore, TM treatment significantly reduced tumor growth in A2780-SP xenograft mice. Voltage gated calcium channels (VGCC) and calcium-activated potassium channels (BKCa) were overexpressed on ovarian CSCs and targeted by TM; inhibition of both channels reduced A2780-SP cells viability. TM reduced stemness-related protein expression; this tendency was reproduced by the simultaneous inhibition of VGCC and BKCa compared to single channel inhibition. In addition, TM suppressed the Wnt/β-catenin, Notch, and Hedgehog pathways which contribute to many CSCs characteristics. Specifically, further suppression of the Wnt/β-catenin pathway by simultaneous inhibition of BKCa and VGCC is necessary for the effective and selective action of TM. Taken together, TM is a potential therapeutic drug for preventing ovarian cancer recurrence and drug resistance.


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