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Therapeutic Gene Delivery and Transfection in Human Pancreatic Cancer Cells using Epidermal Growth Factor Receptor-targeted Gelatin Nanoparticles
Published on: January 4, 2012
Translational research of a novel humanized epidermal growth factor receptor-related protein: a putative inhibitor of
Xian-Hua Fu1, Jun Li, Jian-Jin Huang
1Cancer Institute, Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education, The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou, Zhejiang Province 310009, People's Republic of China.
Purpose:
The ErbB family members are protein tyrosine kinases, which play a crucial role in the signal transduction pathways that regulate key cellular functions. Overexpression of the ErbB family members is associated with oncogenicity, metastatic potential, cell proliferation, apoptosis, angiogenesis, and prognosis in cancer. Molecular-targeted therapies centered on the ErbB signaling pathway are the currently promising anti-cancer therapies.
Methods:
We reviewed the literature to summarize the current knowledge of epidermal growth factor receptor (EGFR)-related protein (ERRP) and determine the potential of this protein to be translated into a molecular-targeting treatment for cancer.
Results:
ERRP isolated from rat gastroduodenal mucosa is a pan-ErbB inhibitor that targets multiple members of the ErbB family both in vitro and in vivo. Sequestration of ErbB ligands by ERRP results in the formation of inactive ErbB heterodimers and subsequent attenuation of signaling pathways activated by ErbB. We suggest a strategy to develop a humanized ERRP protein based on activity of rat EERP in vitro.
Conclusions:
As rat ERRP protein is expected to generate an immune response in humans, we propose a hypothesis that a humanized version of ERRP has potential therapeutic value for cancer patients.
Insights
Epidermal growth factor receptor (EGFR)-related protein (ERRP) inhibits multiple ErbB family members, crucial in cancer. A humanized ERRP may offer a novel molecular-targeting cancer therapy.
Area of Science:
- Molecular biology
- Cancer research
- Biochemistry
Background:
- ErbB family proteins are key regulators of cellular functions.
- ErbB pathway dysregulation is linked to cancer development and progression.
- Targeting the ErbB signaling pathway is a promising anti-cancer strategy.
Purpose of the Study:
- To review current knowledge on EGFR-related protein (ERRP).
- To evaluate ERRP's potential as a molecular-targeting cancer therapy.
Main Methods:
- Literature review on ERRP and ErbB signaling.
- Analysis of ERRP's inhibitory activity against ErbB family members.
- Proposal for humanized ERRP development.
Main Results:
- Rat ERRP acts as a pan-ErbB inhibitor in vitro and in vivo.
- ERRP sequesters ErbB ligands, inactivating ErbB heterodimers and downstream signaling.
- A strategy for developing humanized ERRP based on rat ERRP activity was proposed.
Conclusions:
- Rat ERRP is a potent inhibitor of the ErbB family.
- A humanized ERRP is hypothesized to have therapeutic potential for cancer.
- Humanized ERRP could represent a novel molecular-targeting cancer treatment.
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