Targeting the IGF-1R in prostate and colorectal cancer: reasons behind trial failure and future directions

2022 ◽  
Author(s):  
Muhammad Tufail ◽  
Changxin Wu
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Predictive Biomarkers ◽  
Cancer Growth ◽  
Pharmaceutical Companies ◽  
Future Directions ◽  
System Complexity ◽  
Deadly Disease ◽  
Trial Failure ◽  
Shed Light

IGF-1Rs enact a significant part in cancer growth and its progress. IGF-1R inhibitors were encouraged in the early trials, but the patients did not benefit due to the unavailability of predictive biomarkers and IGF-1R system complexity. However, the linkage between IGF-1R and cancer was reported three decades ago. This review will shed light on the IGF-1R system, targeting IGF-1R through monoclonal antibodies, reasons behind IGF-1R trial failure and future directions. This study presented that targeting IGF-1R through monoclonal antibodies is still effective in cancer treatment, and there is a need to look for future directions. Cancer patients may benefit from using mAbs that target existing and new cancer targets, evidenced by promising results. It is also essential that the academician, trial experts and pharmaceutical companies play their role in finding a treatment for this deadly disease.

scholarly journals Antiepidermal Growth Factor Receptor Monoclonal Antibodies: Applications in Colorectal Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Efat Azizi ◽  
Adam Kittai ◽  
Peter Kozuch
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Growth Factor ◽  
Metastatic Colorectal Cancer ◽  
Kras Mutation ◽  
Poor Prognosis ◽  
Growth Factor Receptor ◽  
Predictive Biomarkers ◽  
Wild Type

Patients with metastatic colorectal cancer have a poor prognosis and present a challenge to clinicians. The role of the antiepidermal growth factor receptor (EGFR) pathway in tumorogenesis and tumor progression has been well defined. This paper will review the use of anti-EGFR monoclonal antibodies in the treatment of operable, as well as metastatic colorectal cancer both in the setting of KRAS mutation unselected patients and later in KRAS wild-type patients. Active investigations designed to further identify predictive biomarkers that may be potentially druggable are reviewed as well.

scholarly journals A Panel of Four Anti-HSPG Monoclonal Antibodies Benefits in Increasing the Specificity in Detection of Colorectal Cancer

2021 ◽  
Vol 20 (3) ◽  
Author(s):  
Ei Khaing Mon ◽  
Rujurek Chaiwongsa ◽  
Phennapha Klangsinsirikul ◽  
Preeyanat Vongchan
Keyword(s):  
Colorectal Cancer ◽  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
Cell Lines ◽  
Cancer Cell ◽  
Blood Cells ◽  
White Blood Cells ◽  
Predictive Biomarkers ◽  
Future Research ◽  
Tumor Cell Lines

Colorectal cancer (CRC) is the second leading with main cause of death is liver and lung metastasis. Using of a combination of genetic and epigenetic markers are addressed but the results have not been approved in clinical practice. A set of serum biomarkers has been proposed to increase accuracy in early diagnosis of CRC. In addition, non-invasive as well as the best prognostic panel of biomarkers and define predictive biomarkers for treatment of CRC are all aims of future research. HSPGs is an important biomolecule involving in cancer cell proliferation, differentiation, and migration. Membrane HSPGs shed into blood circulation and matrix in particular circumstance can be used as a specific biomarker for some cancer cells. In order to evaluate the benefit of a panel of anti-HSPGs monoclonal antibodies in increasing specificity to detect CRC, four clones of anti-HSPGs were studied for its specific reaction on various tumor cell lines by indirect immunofluorescent technique and analyzed by flow cytometer compared to normal white blood cells. A combination of two or more clones were focused. The results showed that all four clones presented a variation in reaction to all solid tumor cell lines tested but negative to normal white blood cells from different ABO blood groups. Interestingly, amongst those cells tested, HT29, a colorectal cancer cell lines were significantly reacted with all four monoclonal antibodies. Taken together, we proposed a panel of four anti-HSPGs monoclonal antibodies to be applied in various detection platforms to increase the specificity in screening of CRC. Keywords: Cancer biomarkers, Colorectal cancer, HSPG

A Critical Review of Second-generation anti-EGFR Monoclonal Antibodies in Metastatic Colorectal Cancer

2020 ◽  
Vol 21 ◽  
Author(s):  
Daniel Sur ◽  
Andrei Havasi ◽  
Alecsandra Gorzo ◽  
Claudia Burz
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Clinical Trials ◽  
Monoclonal Antibodies ◽  
Metastatic Colorectal Cancer ◽  
Second Generation ◽  
Current Data ◽  
Braf Mutations ◽  
Durable Response ◽  
Ongoing Research

Background: Anti-EGFR monoclonal antibodies (mAbs) have become a relevant solution for the treatment of patients with metastatic colorectal cancer. Current anti-EGFR monoclonal antibodies face a series of problems, including resistance and non-durable response, and RAS and BRAF mutations serve as exclusion criteria for treatment with anti-EGFR mAbs. Advances in molecular tumor profiling and information on subsequent pathways responsible for disease progression and drug resistance helped develop a new generation of anti-EGFR mAbs. These second-generation mAbs have been developed to overcome existing resistance mechanisms and to limit common side effects. For the moment, existing literature suggests that these novel anti-EGFR mAbs are far from finding their way to clinical practice soon. Objective: In this review, we summarize and evaluate current data regarding ongoing research and completed clinical trials for different second-generation anti-EGFR monoclonal antibodies. Conclusion: Anti-EGFR mAbs exhibit efficacy in advanced colorectal cancer, but second-generation mAbs failed to prove their benefit in the treatment of metastatic colorectal cancer. Understanding the biological basis of primary and acquired drug resistance could allow scientists to design better clinical trials and develop improved second-generation mAbs.

Free Fatty Acid Receptors as New Potential Targets in Colorectal Cancer

2020 ◽  
Vol 21 (14) ◽  
pp. 1397-1404
Author(s):  
Adrian Bartoszek ◽  
Jakub Fichna ◽  
Aleksandra Tarasiuk ◽  
Agata Binienda ◽  
Adam Fabisiak ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Current Knowledge ◽  
Developed Countries ◽  
Future Directions ◽  
Screening Programs ◽  
Pharmacological Targets ◽  
The Family ◽  
Free Fatty Acid Receptors

Colorectal cancer (CRC) is one of the most common cancers worldwide. In developed countries, its mortality remains high, yet the prevalence has established owing to effective screening programs; however due to the westernization of lifestyle, the incidences in many other countries have increased. Although the treatment of CRC has improved in the last few years, the side effects of these approaches cannot be neglected. Recently, members of the family of free fatty acid receptors (FFARs) have become attractive pharmacological targets in many diseases, including asthma; studies also point to their role in carcinogenesis. Here, we discuss current knowledge and future directions in FFAR research related to CRC. Contradictory results of FFARs modulation may derive from the pleiotropic effects of FFAR ligands, receptor distribution and different signal transduction. Hence, we indicate directions of further studies to fully use the potential of FFARs in CRC.

scholarly journals Monoclonal antibodies and chimeric antigen receptor (CAR) T cells in the treatment of colorectal cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ke-Tao Jin ◽  
Bo Chen ◽  
Yu-Yao Liu ◽  
H uan-Rong Lan ◽  
Jie-Ping Yan
Keyword(s):  
Colorectal Cancer ◽  
T Cells ◽  
Monoclonal Antibodies ◽  
Immune Responses ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
Therapeutic Approaches ◽  
Great Ability ◽  
Car T Cells ◽  
Car T

AbstractColorectal cancer (CRC) is the third most common cancer and the second leading cause of cancer deaths worldwide. Besides common therapeutic approaches, such as surgery, chemotherapy, and radiotherapy, novel therapeutic approaches, including immunotherapy, have been an advent in CRC treatment. The immunotherapy approaches try to elicit patients` immune responses against tumor cells to eradicate the tumor. Monoclonal antibodies (mAbs) and chimeric antigen receptor (CAR) T cells are two branches of cancer immunotherapy. MAbs demonstrate the great ability to completely recognize cancer cell-surface receptors and blockade proliferative or inhibitory pathways. On the other hand, T cell activation by genetically engineered CAR receptor via the TCR/CD3 and costimulatory domains can induce potent immune responses against specific tumor-associated antigens (TAAs). Both of these approaches have beneficial anti-tumor effects on CRC. Herein, we review the different mAbs against various pathways and their applications in clinical trials, the different types of CAR-T cells, various specific CAR-T cells against TAAs, and their clinical use in CRC treatment.

scholarly journals Baseline and Kinetic Circulating Tumor Cell Counts Are Prognostic Factors in a Prospective Study of Metastatic Colorectal Cancer

Diagnostics ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 502
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Angelo Borsarelli Carvalho de Brito ◽  
Alexcia Camila Braun ◽  
Milena Shizue Tariki ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Resistance ◽  
Prospective Study ◽  
Metastatic Colorectal Cancer ◽  
Clinical Outcomes ◽  
Predictive Biomarkers ◽  
Multi Drug Resistance ◽  
Cell Counts ◽  
Potential Clinical Benefit ◽  
A Prospective Study

The discovery of predictive biomarkers in metastatic colorectal cancer (mCRC) is essential to improve clinical outcomes. Recent data suggest a potential role of circulating tumor cells (CTCs) as prognostic indicators. We conducted a follow-on analysis from a prospective study of consecutive patients with mCRC. CTC analysis was conducted at two timepoints: baseline (CTC1; before starting chemotherapy), and two months after starting treatment (CTC2). CTC isolation/quantification were completed by ISET® (Rarecells, France). CTC expressions of drug resistance-associated proteins were evaluated. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan–Meier method. Seventy-five patients were enrolled from May 2012 to May 2014. A CTC1 cut-off of >1.5 CTCs/mL was associated with an inferior median OS compared to lower values. A difference of CTC2−CTC1 > 5.5 CTCs/mL was associated with a reduced median PFS. By multivariate analysis, CTC1 > 1.5 CTCs/mL was an independent prognostic factor for worse OS. Multi-drug resistance protein-1 (MRP-1) expression was associated with poor median OS. CTC baseline counts, kinetics, and MRP-1 expression were predictive of clinical outcomes. Larger studies are warranted to explore the potential clinical benefit of treating mCRC patients with targeted therapeutic regimens guided by CTC findings.

scholarly journals Security Vulnerabilities of SGX and Countermeasures

2021 ◽  
Vol 54 (6) ◽  
pp. 1-36
Author(s):  
Shufan Fei ◽  
Zheng Yan ◽  
Wenxiu Ding ◽  
Haomeng Xie
Keyword(s):  
Operating System ◽  
Security Risks ◽  
Security Vulnerabilities ◽  
Future Directions ◽  
High Security ◽  
Secure Hardware ◽  
Run Time ◽  
Shed Light

Trusted Execution Environments (TEEs) have been widely used in many security-critical applications. The popularity of TEEs derives from its high security and trustworthiness supported by secure hardware. Intel Software Guard Extensions (SGX) is one of the most representative TEEs that creates an isolated environment on an untrusted operating system, thus providing run-time protection for the execution of security-critical code and data. However, Intel SGX is far from the acme of perfection. It has become a target of various attacks due to its security vulnerabilities. Researchers and practitioners have paid attention to the security vulnerabilities of SGX and investigated optimization solutions in real applications. Unfortunately, existing literature lacks a thorough review of security vulnerabilities of SGX and their countermeasures. In this article, we fill this gap. Specifically, we propose two sets of criteria for estimating security risks of existing attacks and evaluating defense effects brought by attack countermeasures. Furthermore, we propose a taxonomy of SGX security vulnerabilities and shed light on corresponding attack vectors. After that, we review published attacks and existing countermeasures, as well as evaluate them by employing our proposed criteria. At last, on the strength of our survey, we propose some open challenges and future directions in the research of SGX security.

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