HER2 overexpression and cancer targeting

2001 ◽  
Vol 28 (5N) ◽  
pp. 115-124 ◽  
Author(s):  
Shao-Chun Wang ◽  
Mien-Chie Hung
Keyword(s):  
Cancer Targeting ◽  
Her2 Overexpression

HER2 OVEREXPRESSION IN ENDOSCOPIC BIOPSY SAMPLE OF GASTRIC ADENOCARCINOMA BY IMMUNOHISTOCHEMISTRY

2012 ◽  
pp. 109-118
Author(s):  
Viet Nho Le ◽  
Van Huy Tran ◽  
Cong Thuan Dang ◽  
Van To Ta
Keyword(s):  
Gastric Adenocarcinoma ◽  
Undifferentiated Carcinoma ◽  
Signet Ring Cell Carcinoma ◽  
Signet Ring Cell ◽  
Endoscopic Biopsy ◽  
Her2 Overexpression ◽  
Tubular Adenocarcinoma ◽  
Signet Ring ◽  
Poorly Differentiated ◽  
Well Differentiated

Background and aim: HER2 overexpression by immunohistochemistry is a prognostic maker in gastric cancer and helps to select candidates benefitted from targeted therapy with trastuzumab. This study is aimed at the assessing HER2 overexpression and its relationship with endoscopic and histopathological findings of gastric adenocarcinoma. Objectives and methods: Biopsy samples from 92 gastric cancer patients were examined for HER2 status by immunohistochemical staining. Results: 6.5% of tumors were cardia tumors and 93.5% were non-cardia tumors. Using the Lauren classification, 51.1% were intestinal type and 48.9% were diffuse type. Using WHO classification, 54.3% were tubular adenocarcinoma, 7.6% were mucinous adenocarcinoma, 15.2% were signet-ring cell carcinoma, and 22.8% were undifferentiated carcinoma. 32.6% were well-differentiated, 15.2% were moderately-differentiated, and 52.2% were poorly-differentiated carcinoma. HER2 was positive in 20.7% of gastric carcinomas, 50% cardia tumors and 18.6% non-cardia tumors. HER2 positivity among polypoid, fungating, ulcerated, and infiltrative types were 38.5%, 29.7%, 9.1% and 0%, respectively. HER2 overexpression in intestinal type was higher than that in diffuse type (31.9% vs. 8.9%, p = 0.009). HER2 overexpression in tubular adenocarcinoma, mucinous adenocarcinoma, signet-ring cell carcinoma, and undifferentiated carcinoma was 28.0%, 14.3%, 7.1% and 14.3%, respectively. HER2 overexpressions were different between differentiation degrees: 30% of well-differentiated tumors, 35.7% moderately-differentiated tumors, and 10.4% of poorly-differentiated tumors (p = 0.037). Conclusions: HER2 overexpression was found in 20.7% of endoscopic biopsy sample of gastric adenocarcinoma and was associated with endoscopic gross characteristic, Lauren histologic type and differentiation degree.

scholarly journals Recent Advances of Nanotechnology-Facilitated Bacteria-Based Drug and Gene Delivery Systems for Cancer Treatment

Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 940
Author(s):  
Chaojie Zhu ◽  
Zhiheng Ji ◽  
Junkai Ma ◽  
Zhijie Ding ◽  
Jie Shen ◽  
...  
Keyword(s):  
Gene Delivery ◽  
Cancer Treatment ◽  
Delivery Systems ◽  
Cancer Targeting ◽  
Cancer Treatments ◽  
Recent Advances ◽  
Therapeutic Mechanisms ◽  
Bacterial Therapy ◽  
Targeting Ability ◽  
Drug And Gene Delivery

Cancer is one of the most devastating and ubiquitous human diseases. Conventional therapies like chemotherapy and radiotherapy are the most widely used cancer treatments. Despite the notable therapeutic improvements that these measures achieve, disappointing therapeutic outcome and cancer reoccurrence commonly following these therapies demonstrate the need for better alternatives. Among them, bacterial therapy has proven to be effective in its intrinsic cancer targeting ability and various therapeutic mechanisms that can be further bolstered by nanotechnology. In this review, we will discuss recent advances of nanotechnology-facilitated bacteria-based drug and gene delivery systems in cancer treatment. Therapeutic mechanisms of these hybrid nanoformulations are highlighted to provide an up-to-date understanding of this emerging field.

Evaluation of 99mTc-labeled glutathione as a colon cancer targeting probe

2021 ◽  
Vol 327 (2) ◽  
pp. 673-689
Author(s):  
Sumeera Sidiq ◽  
Ravi Ranjan Kumar ◽  
Neelima D. Passi ◽  
D. K. Dhawan ◽  
Jaya Shukla ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Targeting

scholarly journals Do early HER2-overexpression breast cancer patients benefit from undergoing neoadjuvant trastuzumab and mastectomy? A meta-analysis

2019 ◽  
Vol Volume 11 ◽  
pp. 8043-8054 ◽  
Author(s):  
Lin He ◽  
Qian Wu ◽  
Jing Xiong ◽  
Zhumin Su ◽  
Biyuan Zhang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Meta Analysis ◽  
Her2 Overexpression ◽  
Breast Cancer Patients

scholarly journals Development of a bispecific immune engager using a recombinant malaria protein

2021 ◽  
Vol 12 (4) ◽  
Author(s):  
Mie A. Nordmaj ◽  
Morgan E. Roberts ◽  
Emilie S. Sachse ◽  
Robert Dagil ◽  
Anne Poder Andersen ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Immune Evasion ◽  
Blood Cells ◽  
Xenograft Model ◽  
Cancer Targeting ◽  
Single Chain Variable Fragment ◽  
Single Chain ◽  
Conjugation System ◽  
Immune Mediated

AbstractAs an immune evasion and survival strategy, the Plasmodium falciparum malaria parasite has evolved a protein named VAR2CSA. This protein mediates sequestration of infected red blood cells in the placenta through the interaction with a unique carbohydrate abundantly and exclusively present in the placenta. Cancer cells were found to share the same expression of this distinct carbohydrate, termed oncofetal chondroitin sulfate on their surface. In this study we have used a protein conjugation system to produce a bispecific immune engager, V-aCD3, based on recombinant VAR2CSA as the cancer targeting moiety and an anti-CD3 single-chain variable fragment linked to a single-chain Fc as the immune engager. Conjugation of these two proteins resulted in a single functional moiety that induced immune mediated killing of a broad range of cancer cells in vitro and facilitated tumor arrest in an orthotopic bladder cancer xenograft model.

810 Preliminary safety, tolerability and efficacy results of KN026 in combination with KN046 in patients with HER2 aberrated solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A861-A861
Author(s):  
Jifang Gong ◽  
Lin Shen ◽  
Zhi Dong ◽  
Dan Liu ◽  
June Xu ◽  
...  
Keyword(s):  
Disease Progression ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Bispecific Antibody ◽  
Her2 Overexpression ◽  
Her2 Positive ◽  
Her2 Mutation ◽  
Grade 3 ◽  
Experienced Grade ◽  
Low Expression

BackgroundHER2 potently inhibits innate immunity through cGAS–STING signaling [Ref],meanwhile HER2 antibody induced ADCP will also lead to macrophage mediated immune suppression. Both preclinical and clinical studies have suggested a coordination of engagement of innate and adaptive immunity with the combination of an anti-HER2 antibody and an immune checkpoint blockade. KN026 is a novel bispecific antibody that simultaneously binds to two distinct HER2 epitopes. KN046 is a novel bispecific antibody that blocks both PD-L1 interaction with PD-1/CD80 and CTLA-4 interaction with CD80/CD86. Here we reported the interim results from an ongoing phase Ib dose escalation and expansion study assessing the safety, tolerability and preliminary efficacy for KN026 in combination with KN046 in Patients with HER2 aberrated solid tumors.MethodsThis study enrolled pts with solid tumors who failed available standard of care, HER2 aberration status confirmed locally (HER2 mutation, HER2 amplification and/or HER2 overexpression). Eligible pts received combination of KN026 and KN046 at three dose levels until disease progression, unacceptable toxicity or withdrawal of informed consent (DL1: KN026 20 mg/kg Q2W + KN046 3 mg/kg Q2W; DL2: KN026 20 mg/kg Q2W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W; DL3: KN026 30 mg/kg Q3W with loading on Days 1, 8 of Cycle 1 + KN046 5 mg/kg Q3W). Tumor response was evaluated Q8W per RECIST 1.1. Primary endpoint was DLT and key secondary endpoints were efficacy parameters (ORR, DOR, PFS).ResultsAs of the Sep. 08, 2020, 25 pts were enrolled into DL1 (n = 20, 3 for dose escalation), DL2 (n = 3) and DL3 (n = 2) (mGC/GEJ 15 pts; mCRC 8 pts; other solid tumors 2 pts). 15 pts remained on the study treatment and 10 pts discontinued treatment due to disease progression (n=5), death (n=2) and other reasons (n=3). 18 pts had HER2-positive status (12 of 18 failed previous trastuzumab therapy), 2 pts had HER2 mutation and 5 pts had HER2 low expression (without FISH amplification). No DLTs were observed. No pts experienced LVEF decreased or other clinically meaningful cardiac AEs. Treatment-related TEAEs occurred in 23 (92%) pts, of which 6 (24%) pts experienced grade 3 or above treatment-related TEAEs. 11 (44%) pts experienced irAEs, majority were of grade 1 or 2 except that 1 patient experienced grade 3 immune-mediated endocrinopathy. The most common (frequency ≥ 15%) KN026 or KN046 related TEAEs were infusion related reaction (n=11, 44.0%), anaemia (n=9, 36.0%), white blood cell count decreased (n=6, 24.0%), diarrhea (n=5, 20.0%), AST increased (n=5, 20.0%), platelet count decreased (n=5, 20.0%), rash (n=5, 20.0%) and ALT increased (n=4, 16.0%). The objective response rate in pts with HER2-positive tumors (n = 14 efficacy evaluable pts) was 9/14 (64.3%, 95% CI 35.1~87.2%) and disease control rate 13/14 (92.9%, 95% CI 66.1~99.8%). 4 out of 5 pts with HER2 mutation or low expression achieved SD including one patient with SD for more than 24 weeks. 2 death cases due to disease progression were reported, both only received one cycle of KN026 plus KN046 due to COVID-19 restriction.ConclusionsKN026 combined with KN046 is well tolerated and has demonstrated preliminary albeit profound anti-tumor activity in HER2-positive solid tumors.Trial RegistrationClinical trial information: NCT04040699ReferenceShiying Wu, Qian Zhang, Fei Zhang, et al. HER2 recruits AKT1 to disrupt STING signalling and suppress antiviral defence and antitumour immunity. Nature Cell Biology 2019;21:1027–1040.

Importance of local glycan heterogeneity for in vivo cancer targeting

2021 ◽  
pp. 153089
Author(s):  
Ivan Smirnov ◽  
Igor Nasibullin ◽  
Almira Kurbangalieva ◽  
Katsunori Tanaka
Keyword(s):  
Cancer Targeting ◽  
Glycan Heterogeneity

Mussel-Derived, Cancer-Targeting Peptide as pH-Sensitive Prodrug Nanocarrier

2019 ◽  
Vol 11 (27) ◽  
pp. 23948-23956 ◽  
Author(s):  
Yue Ma ◽  
Peiyan He ◽  
Xiaohua Tian ◽  
Guanglei Liu ◽  
Xiaowei Zeng ◽  
...  
Keyword(s):  
Ph Sensitive ◽  
Cancer Targeting ◽  
Targeting Peptide

Combined Multi-Target Molecular Ultrasonography and Photothermal Therapy Using Cancer Targeting Gold Nano Rod Probes

2008 ◽  
Author(s):  
Dar-Bin Shieh ◽  
An An Ding ◽  
Ya-Na Wu ◽  
Ying-Yi Chen ◽  
Churng-Ren Chris Wang ◽  
...  
Keyword(s):  
Photothermal Therapy ◽  
Cancer Targeting
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