Generation of Antibody-Drug Conjugate Resistant Models

Gandullo-Sánchez, Lucía; Ocaña, Alberto; Pandiella, Atanasio

doi:10.3390/cancers13184631

Cited by 11 publications

(6 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These ndings suggest that E2F7 promotes drug resistance by affecting the ability of cells to uptake drugs and facilitating drug e ux mediated by ABC transporters. The activation of expulsion pumps, such as ABC transporters, can lead to the development of multidrug resistance (MDR) [35,36]. Therefore, we propose that E2F7 in uenced the ability of uptake drugs by promoting e ux action in cells, ultimately resulting in the development of drug resistance.…”

Section: Discussionmentioning

confidence: 99%

E2F7 as a Dual Regulator of Tumor Suppression and Chemoresistance in Glioblastoma multiforme

Meng,

Qian,

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

Background Glioblastoma multiforme (GBM) is the most aggressive form of brain cancer, and chemoresistance poses a significant challenge to the survival and prognosis of GBM. Although numerous regulatory mechanisms contributing to chemoresistance have been identified, many questions remain unanswered. This study aims to identify the mechanism of temozolomide (TMZ) resistant in GBM. Methods Since a temozolomide (TMZ) resistance model in vivo has been published in our group, the present study has employed transcriptome sequencing and experiments to analyze the function of E2F7 in GBM during the TMZ treatment, and the ChIPBase and PROMO database was used to explore the upregulators of E2F7 in TMZ resistance tumors, further in vivo and in vitro experiments are required to confirm the results. Results The study revealed that E2F7 was significantly upregulated in TMZ resistant tumors, high expression of E2F7 inhibited GBM tumorigenesis and growth, and promoted chemoresistance by reducing drug uptake and facilitating efflux. Furthermore, we observed increased phosphorylation and activation of the p53 protein in TMZ-resistant tumors, which directly contributed to the transcriptional upregulation of E2F7. Conclusions E2F7 serves as a poor prognostic indicator for GBM, and potentially plays a crucial role in promotion of TMZ resistance, and the activation of the p53 protein in these TMZ resistance, which directly contributed to the transcriptional upregulation of E2F7.

show abstract

Section: Discussionmentioning

confidence: 99%

E2F7 as a Dual Regulator of Tumor Suppression and Chemoresistance in Glioblastoma multiforme

Meng,

Qian,

Yang

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…ADCs are a novel class of anti-cancer drugs with significant potential in HER3-targeted therapy. ADCs are composed of targeted mAbs that are chemically linked to cytotoxic drugs, either cleavable or non-cleavable [ 109 ]. The mAb component of ADCs binds to specific antigens on the surface of cancer cells, resulting in the internalization of ADCs [ 110 ].…”

Section: Targeting Her3 To Treat Mbcmentioning

confidence: 99%

HER3 receptor and its role in the therapeutic management of metastatic breast cancer

Zhu,

Yu,

Meng

et al. 2024

J Transl Med

View full text Add to dashboard Cite

Metastatic breast cancer (mBC) poses a significant threat to women's health and is a major cause of malignant neoplasms in women. Human epidermal growth factor receptor (HER)3, an integral member of the ErbB/HER receptor tyrosine kinase family, is a crucial activator of the phosphoinositide-3 kinase/protein kinase B signaling pathway. HER3 overexpression significantly contributes to the development of resistance to drugs targeting other HER receptors, such as HER2 and epidermal growth factor receptors, and plays a crucial role in the onset and progression of mBC. Recently, numerous HER3-targeted therapeutic agents, such as monoclonal antibodies (mAbs), bispecific antibodies (bAbs), and antibody–drug conjugates (ADCs), have emerged. However, the efficacy of HER3-targeted mAbs and bAbs is limited when used individually, and their combination may result in toxic adverse effects. On the other hand, ADCs are cytotoxic to cancer cells and can bind to target cells through antibodies, which highlights their use in targeted HER3 therapy for mBC. This review provides an overview of recent advancements in HER3 research, historical initiatives, and innovative approaches in targeted HER3 therapy for metastatic breast cancer. Evaluating the advantages and disadvantages of current methods may yield valuable insights and lessons.

show abstract

“…ADCs are a new class of antitumoral agents designed to merge the selectivity of mAbs with the cell killing properties of a cytotoxic drug (payload) attached by a linker to the mAb. That linker may be cleavable or non-cleavable [232,233].…”

Section: Antibody-drug Conjugatesmentioning

confidence: 99%

HER3 in cancer: from the bench to the bedside

Gandullo-Sánchez

Ocaña

Pandiella

2022

J Exp Clin Cancer Res

Self Cite

View full text Add to dashboard Cite

The HER3 protein, that belongs to the ErbB/HER receptor tyrosine kinase (RTK) family, is expressed in several types of tumors. That fact, together with the role of HER3 in promoting cell proliferation, implicate that targeting HER3 may have therapeutic relevance. Furthermore, expression and activation of HER3 has been linked to resistance to drugs that target other HER receptors such as agents that act on EGFR or HER2. In addition, HER3 has been associated to resistance to some chemotherapeutic drugs. Because of those circumstances, efforts to develop and test agents targeting HER3 have been carried out. Two types of agents targeting HER3 have been developed. The most abundant are antibodies or engineered antibody derivatives that specifically recognize the extracellular region of HER3. In addition, the use of aptamers specifically interacting with HER3, vaccines or HER3-targeting siRNAs have also been developed. Here we discuss the state of the art of the preclinical and clinical development of drugs aimed at targeting HER3 with therapeutic purposes.

show abstract

Generation of Antibody-Drug Conjugate Resistant Models

Cited by 11 publications

References 75 publications

E2F7 as a Dual Regulator of Tumor Suppression and Chemoresistance in Glioblastoma multiforme

E2F7 as a Dual Regulator of Tumor Suppression and Chemoresistance in Glioblastoma multiforme

HER3 receptor and its role in the therapeutic management of metastatic breast cancer

HER3 in cancer: from the bench to the bedside

Contact Info

Product

Resources

About