EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles

Santos, Elias da Silva; Nogueira, Karina Alexandre Barros; Fernandes, Luiziana Cavalcante Costa; Martins, Jéssica Roberta Pereira; Reis, Alice Vitória Frota; Neto, José de Brito Vieira; Júnior, Ivanildo José da Silva; Pessoa, Cláudia; Petrilli, Raquel; Eloy, Josimar O.

doi:10.1016/j.ijpharm.2020.120082

Cited by 102 publications

(65 citation statements)

References 147 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5D ) ( 9 ), particularly in metastasis and stemness ( 7 , 10 ). EGFR and IGF1R function as oncogenes and promote the development and progression of numerous cancer types ( 50 , 51 ). PI3K/AKT signaling is one of the most critical cancer-promoting pathways through the upregulation of tyrosine kinase receptors ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

et al. 2021

View full text Add to dashboard Cite

Ubiquilin-1 (UBQLN1) is an essential factor for the maintenance of proteostasis in cells. It is important for the regulation of different protein degradation mechanisms, including the ubiquitin-proteasome system, autophagy and endoplasmic reticulum-associated protein degradation pathways. However, the role of UBQLN1 in cancer progression remains largely unknown. In the present study, the expression, functions and molecular mechanisms of UBQLN1 in breast cancer tissue samples and cell lines were explored. Immunohistochemical and bioinformatics analyses revealed that UBQLN1 expression was significantly upregulated in breast cancer tissues and cell lines. UBQLN1 expression in breast cancer was significantly associated with lymph node metastasis and TNM stage. Moreover, a high UBQLN1 expression was a predictor of an unfavorable survival in patients with breast cancer. In vitro, UBQLN1 silencing markedly inhibited cell migration and invasion, epithelial-to-mesenchymal transition (EMT) and MMP expression. UBQLN1 silencing attenuated the stem cell-like properties of breast cancer cells, including their mammosphere-forming abilities. UBQLN1 knockdown also enhanced breast cancer cell chemosensitivity to paclitaxel. The expression levels of the stem cell markers.Aldehyde dehydrogenase 1 (ALDH1), Oct-4 and Sox2 were significantly decreased in the cells in which UBQLN1 was silenced, whereas breast cancer stem cells exhibited an increased expression of UBQLN1. Mechanistically, UBQLN1 knockdown inhibited the activation of AKT signaling, as revealed by the increased PTEN expression and the decreased expression of phosphorylated AKT in cells in which UBQLN1 was silenced. On the whole, the present study demonstrates that UBQLN1 is aberrantly upregulated in breast cancer and predicts a poor prognosis. The silencing of UBQLN1 inhibited the invasion, EMT and stemness of breast cancer cells, possibly via AKT signaling.

show abstract

Section: Discussionmentioning

confidence: 99%

Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Inhibition of EGFR causes many cellular effects and causes antitumor responses so that there is a lot of evidence that EGFR inhibitors are useful for cancer therapy. 22,26,27 The study conducted by Sabrina Oliveira et al in 2006 showed that blocking of EGFR signaling pathways alone could not inhibit cell proliferation. The cancer cells may use multiple intracellular pathways to overcome the blockage of specific receptors.…”

Section: Discussionmentioning

confidence: 99%

Production and Verification of Anti-Tumor Activity of Monoclonal Anti-EGFR-Recombinant PE38 Immunotoxin in A431 Tumor Cells

2021

View full text Add to dashboard Cite

Background: Tumor growth and progression depend largely on the activity of cell membrane receptors like epidermal growth factor receptor (EGFR). This receptor plays a significant role in the growth and survival of many solid tumors. Its biological feature makes it a highly appealing target for cancer treatment. On the other hand, immunotherapy is an efficient approach in cancer treatment, and immunotoxins have a predominant position herein. Thus, this approach can be used in high EGFR-expressed cancer therapy. Methods: In this study, the production of monoclonal anti-EGFR-recombinant PE38 was used as the special treatment against EGFR-activated cancers. For this purpose, the A431 cell line originating from a squamous carcinoma was used. In order the production of this immunotoxin, the toxin was conjugated with an antibody by chemical method. To confirm conjugation and its purity, SDS-PAGE was performed by immunotoxin electrophoresis. Then, the antitumor effects of immunotoxin in the induction of apoptosis of tumoral cells were assessed by the ELISA method. Results: The conjugation and purity of immunotoxin were confirmed by immunotoxin electrophoresis. Also, the ELISA results indicate that the produced immunotoxin induced 62% antigen-specific apoptosis (P <0.0001) in tumoral cells compared to the control cells. Conclusion: To conclude, our study provides a promising therapeutic approach against EGFR-associated cancers and our individual immunotoxin can be used in the treatment of tumors with membranous EGFR.

show abstract

“…A partial but long-lasting response was observed when combination therapy with trastuzumab–pertuzumab was used in a young woman with high-grade serous ovarian cancer (FIGO stage IV) [ 15 ]. Furthermore, a number of EGF-R targeting agents are currently in clinical trials [ 105 , 106 , 107 ], while some agents have shown exciting antitumor performance in CRC-based xenograft models and cell lines, such as cabozantinib, and are awaiting clinical trials [ 10 ]. Other receptor-binding inhibitors, such as cetuximab, work differently from the TKIs gefitinib and erlotinib.…”

Section: Novel Treatment Strategies For Epithelial Ovarian Cancer (Eoc)mentioning

confidence: 99%

Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

Akter

Rahman

Hasan³

et al. 2022

Cells

View full text Add to dashboard Cite

Aggressive and recurrent gynecological cancers are associated with worse prognosis and a lack of effective therapeutic response. Ovarian cancer (OC) patients are often diagnosed in advanced stages, when drug resistance, angiogenesis, relapse, and metastasis impact survival outcomes. Currently, surgical debulking, radiotherapy, and/or chemotherapy remain the mainstream treatment modalities; however, patients suffer unwanted side effects and drug resistance in the absence of targeted therapies. Hence, it is urgent to decipher the complex disease biology and identify potential biomarkers, which could greatly contribute to making an early diagnosis or predicting the response to specific therapies. This review aims to critically discuss the current therapeutic strategies for OC, novel drug-delivery systems, and potential biomarkers in the context of genetics and molecular research. It emphasizes how the understanding of disease biology is related to the advancement of technology, enabling the exploration of novel biomarkers that may be able to provide more accurate diagnosis and prognosis, which would effectively translate into targeted therapies, ultimately improving patients’ overall survival and quality of life.

show abstract

EGFR targeting for cancer therapy: Pharmacology and immunoconjugates with drugs and nanoparticles

Cited by 102 publications

References 147 publications

Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

Abnormally elevated ubiquilin‑1 expression in breast cancer regulates metastasis and stemness via AKT signaling

Production and Verification of Anti-Tumor Activity of Monoclonal Anti-EGFR-Recombinant PE38 Immunotoxin in A431 Tumor Cells

Recent Advances in Ovarian Cancer: Therapeutic Strategies, Potential Biomarkers, and Technological Improvements

Contact Info

Product

Resources

About