A review of HER2 overexpression and somatic mutations in cancers

Galogre, Michael Igorevich; Rodin, Dmitry; Pyatnitskiy, Mikhail A.; Mackelprang, Melissa; Koman, Igor

doi:10.1016/j.critrevonc.2023.103997

Cited by 17 publications

(8 citation statements)

References 98 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HER2 plays a pivotal role in tumor cell proliferation and metastasis, is found to be implicated in various cancer-poor prognoses, and is associated with aggressive and lethal forms of cancer, including ovarian cancer ( Luo et al, 2018 ; Galogre et al, 2023 ). Since advanced ovarian cancer has considerably higher expression of HER2, TAT using Trastuzumab could be a promising strategy to reduce the tumor burden for ovarian cancer.…”

Section: Discussionmentioning

confidence: 99%

Pb-214/Bi-214-TCMC-Trastuzumab inhibited growth of ovarian cancer in preclinical mouse models

Metebi,

Kauffman,

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

Introduction: Better treatments for ovarian cancer are needed to eliminate residual peritoneal disease after initial debulking surgery. The present study evaluated Trastuzumab to deliver Pb-214/Bi-214 for targeted alpha therapy (TAT) for HER2-positive ovarian cancer in mouse models of residual disease. This study is the first report of TAT using a novel Radon-222 generator to produce short-lived Lead-214 (Pb-214, t1/2 = 26.8 min) in equilibrium with its daughter Bismuth-214 (Bi-214, t1/2 = 19.7 min); referred to as Pb-214/Bi-214. In this study, Pb-214/Bi-214-TCMC-Trastuzumab was tested.Methods: Trastuzumab and control IgG antibody were conjugated with TCMC chelator and radiolabeled with Pb-214/Bi-214 to yield Pb-214/Bi-214-TCMC-Trastuzumab and Pb-214/Bi-214-TCMC-IgG1. The decay of Pb-214/Bi-214 yielded α-particles for TAT. SKOV3 and OVAR3 human ovarian cancer cell lines were tested for HER2 levels. The effects of Pb-214/Bi-214-TCMC-Trastuzumab and appropriate controls were compared using clonogenic assays and in mice bearing peritoneal SKOV3 or OVCAR3 tumors. Mice control groups included untreated, Pb-214/Bi-214-TCMC-IgG1, and Trastuzumab only.Results and discussion: SKOV3 cells had 590,000 ± 5,500 HER2 receptors/cell compared with OVCAR3 cells at 7,900 ± 770. In vitro clonogenic assays with SKOV3 cells showed significantly reduced colony formation after Pb-214/Bi-214-TCMC-Trastuzumab treatment compared with controls. Nude mice bearing luciferase-positive SKOV3 or OVCAR3 tumors were treated with Pb-214/Bi-214-TCMC-Trastuzumab or appropriate controls. Two 0.74 MBq doses of Pb-214/Bi-214-TCMC-Trastuzumab significantly suppressed the growth of SKOV3 tumors for 60 days, without toxicity, compared with three control groups (untreated, Pb-214/Bi-214-TCMC-IgG1, or Trastuzumab only). Mice-bearing OVCAR3 tumors had effective therapy without toxicity with two 0.74 MBq doses of Pb-214/Bi-214-TCMC-trastuzumab or Pb-214/Bi-214-TCMC-IgG1. Together, these data indicated that Pb-214/Bi-214 from a Rn-222 generator system was successfully applied for TAT. Pb-214/Bi-214-TCMC-Trastuzumab was effective to treat mouse xenograft models. Advantages of Pb-214/Bi-214 from the novel generator systems include high purity, short half-life for fractioned therapy, and hourly availability from the Rn-222 generator system. This platform technology can be applied for a variety of cancer treatment strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Pb-214/Bi-214-TCMC-Trastuzumab inhibited growth of ovarian cancer in preclinical mouse models

Metebi,

Kauffman,

et al. 2024

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…HER2 is overexpressed in up to 20-30% of breast cancer patients as well in several other malignancies including gastric and gastro-esophageal cancer, colorectal cancer, ovarian cancer, prostate cancer, and lung cancer. 22 – 24 While HER2 can be reliably assessed using IHC, indeterminate staining with IHC (2+) is typically reflexed to FISH. Other predictive/prognostic FISH-based biomarkers that are frequently used in clinical practice include ALK, ROS1, NTRK , rearranged during transfection ( RET ) and MET proto-oncogene, receptor tyrosine kinase ( MET ).…”

Section: The Evaluation Of Molecular Techniques For Biomarker Analysismentioning

confidence: 99%

Cancer biomarkers: Emerging trends and clinical implications for personalized treatment

Passaro,

Al Bakir,

Hamilton

et al. 2024

Cell

View full text Add to dashboard Cite

“…Human epidermal growth factor receptor 2 (HER-2) is a receptor tyrosine kinase receptor encoded by the ERBB2 gene. Application of the HER-2 gene leads to downstream upregulation of key receptor signaling pathways that contribute to cellular growth and proliferation [ 32 ]. HER-2 targeting agents have been deployed across multiple solid tumors, including breast and gastric, with significant clinical benefit and efficacy.…”

Section: Molecular Targetsmentioning

confidence: 99%

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review

Hadfield,

DeCarli,

Bash

et al. 2023

IJMS

View full text Add to dashboard Cite

Cholangiocarcinoma is a malignancy of the bile ducts that is often associated with late diagnosis, poor overall survival, and limited treatment options. The standard of care therapy for cholangiocarcinoma has been cytotoxic chemotherapy with modest improvements in overall survival with the addition of immune checkpoint inhibitors. The discovery of actionable mutations has led to the advent of targeted therapies against FGFR and IDH-1, which has expanded the treatment landscape for this patient population. Significant efforts have been made in the pre-clinical space to explore novel immunotherapeutic approaches, as well as antibody–drug conjugates. This review provides an overview of the current landscape of treatment options, as well as promising future therapeutic targets.

show abstract

A review of HER2 overexpression and somatic mutations in cancers

Cited by 17 publications

References 98 publications

Pb-214/Bi-214-TCMC-Trastuzumab inhibited growth of ovarian cancer in preclinical mouse models

Pb-214/Bi-214-TCMC-Trastuzumab inhibited growth of ovarian cancer in preclinical mouse models

Cancer biomarkers: Emerging trends and clinical implications for personalized treatment

Current and Emerging Therapeutic Targets for the Treatment of Cholangiocarcinoma: An Updated Review

Contact Info

Product

Resources

About