scholarly journals EphB2 as a Therapeutic Antibody Drug Target for the Treatment of Colorectal Cancer

2004 ◽  
Vol 64 (3) ◽  
pp. 781-788 ◽  
Author(s):  
Weiguang Mao ◽  
Elizabeth Luis ◽  
Sarajane Ross ◽  
Johnny Silva ◽  
Christine Tan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Drug Target ◽  
Therapeutic Antibody ◽  
Antibody Drug

scholarly journals SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1

2020 ◽  
Author(s):  
Cong Tian ◽  
Tingyuan Lang ◽  
Jiangfeng Qiu ◽  
Kun Han ◽  
Lei Zhou ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Stem Cells ◽  
Protein Level ◽  
Drug Target ◽  
Target Genes ◽  
Xenograft Model ◽  
Luciferase Reporter ◽  
Hippo Signaling ◽  
Self Renewal ◽  
Underlying Mechanisms

Abstract Background: Cancer stem cells (CSCs) have been recognized as an important drug target, however, the underlying mechanisms have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 promotes colorectal cancer (CRC) stem cells (CRC-SCs) and the underlying mechanisms have remained elusive. Methods: Human CRC cell lines and primary human CRC cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels of target genes were examined by qRT-PCR and western blot. The sphere-forming and in vitro migration capacities were determined by sphere formation and transwell assay. The self-renewal was determined by limiting dilution assay. The tumorigenicity and metastasis of cancer cells were examined by xenograft model. The promoter activity was examined by luciferase reporter assay. Nuclear run-on and Chromatin immunoprecipitation-PCR (ChIP-PCR) assay were employed to examine the transcription and protein-DNA interaction. Co-immunoprecipitation assay was used to test protein-protein interaction. The relationship between gene expression and survival was analyzed by Kaplan-meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± s.d. and the significance was determined by Student’s t-test.Results: SKP1 was upregulated in CRC-SCs and predicted poor prognosis of colon cancer patients. Overexpression of SKP1 promoted the stemness of CRC cells reflected by increased sphere-forming, migration and self-renewal capacities as well as the expression of CSCs markers. In contrast, SKP1 depletion produced the opposite effects. SKP1 strengthened YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of CRC cells. SKP1 suppressed RASSF1 at both mRNA and protein level. Overexpression of RASSF1 abolished the effect of SKP1 on YAP activity and CRC stemness. Conclusion: Our results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of CRC cells.

scholarly journals ASCO 2021—an update on metastastic colorectal cancer

2021 ◽  
Author(s):  
Lukas Weiss
Keyword(s):  
Colorectal Cancer ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Circulating Tumor Dna ◽  
Novel Therapies ◽  
Antibody Drug Conjugate ◽  
Her2 Positive ◽  
Integrate Analysis ◽  
Tumor Dna ◽  
Antibody Drug

SummaryThe 2021 ASCO Annual Meeting provided updates on novel therapies in rare subgroups of metastatic colorectal cancer, such as immunotherapy in microsatellite instable colorectal cancer and antibody–drug conjugate therapy in HER2-positive disease. Furthermore, the concept of anti-EGFR rechallenge therapy has received additional momentum with data from the CHRONOS trial in regard to treating patients in later lines as well as how to integrate analysis of circulating tumor DNA in clinical decision-making.

Activity of IMMU-130 anti-CEACAM5-SN-38 antibody-drug conjugate (ADC) on metastatic colorectal cancer (mCRC) having relapsed after CPT-11: Phase I study.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3106-3106 ◽  
Author(s):  
Efrat Dotan ◽  
Jordan Berlin ◽  
Alexander Starodub ◽  
Michael J. Guarino ◽  
Steven J. Cohen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Metastatic Colorectal Cancer ◽  
Phase I Study ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Antibody Drug

A phase Ib/IIa study of NEO-102: A therapeutic antibody for the treatment of advanced pancreatic and colorectal cancer.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 3072-3072
Author(s):  
Sandip Pravin Patel ◽  
Michael Morse ◽  
Muhammad Shaalan Beg ◽  
Nilofer Saba Azad ◽  
Melony A. Beatson ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Therapeutic Antibody ◽  
Phase Ib

Bstrongximab-MMAE, a novel antibody-drug-conjugate for metastatic gastric and pancreatic cancers.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15620-e15620
Author(s):  
William Michael Schopperle
Keyword(s):  
Embryonic Stem ◽  
Tumor Cell Line ◽  
Therapeutic Antibody ◽  
In Vivo Studies ◽  
Tumor Resistance ◽  
Antibody Drug Conjugate ◽  
Drug Conjugate ◽  
Normal Tissues ◽  
Pancreatic Cancers ◽  
Antibody Drug

e15620 Background: As of today, there are no current beneficial clinical therapeutic cancer treatments for advance metastatic gastric or pancreatic cancers. A new approach to finding effective and meaningful drugs to treat these cancers is based an emerging hypothesis that cancer is a reprogramming disease and its origin and development is due to retrograde-like malignant cells with primitive and embryonic characteristics which are responsible for the dissemination of the disease and the almost universal clinical response of tumor resistance when treated with standard current therapies. Methods: A pluripotent human germ cell tumor cell line, TERA-1, was used to isolate and purify embryonic antigens which where used to immunized mice and, with standard B-cell hybridoma technology, to generate monoclonal antibodies. Antibodies were screened by ELISA and SDS-PAGE Western blotting to identify antibodies specific to gastric and pancreatic cancers but not to normal tissues. A second assay was used to screen the potential of the antibodies to function as antibody-drug-conjugate therapeutics against cancer. Results: A lead therapeutic antibody, Bstrongomab, was identified in the antibody screens: it is positive for gastric and pancreatic cancers but does not react with normal tissues. Bstrongomab is an IgG1 monoclonal antibody which has high affinity and specificity to the embryonic target TRA-1-60. TRA-1-60 is a carbohydrate molecule which is highly expressed in normal embryonic stem cells and not expressed in normal tissues but is re-expressed in gastric and pancreatic cancers. Immunohistochemical tissue staining studies show TRA-1-60 is expressed in gastric and pancreatic cancers. Recent published scientific reports confirm this finding. A human/mouse therapeutic version of Bstrongomab was developed - Bstrongximab - and used to generate a novel therapeutic antibody-drug-conjugate with Bstongximab and the toxic payload MMAE (Monomethyl auristatin E). Pre-clinical i n-vitro and in-vivo studies show Bstrongximab-MMAE is a potent drug for gastric and pancreatic cancers. Conclusions: Bstrongximab is a novel IgG1 human/mouse chimeric therapeutic antibody that targets TRA-1-60, a novel and yet to be tried cancer target that is highly expressed in gastric and pancreatic cancers but not in normal tissues. Bstrongximab-MMAE has the potential to be a first-in-class cancer therapeutic that provides real and meaningful benefits to patients with metastatic gastric and pancreatic cancers.

Sign in / Sign up

Export Citation Format

Share Document