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Updated: Jun 4, 2025
Building Up a High-throughput Screening Platform to Assess the Heterogeneity of HER2 Gene Amplification in Breast Cancers
Published on: December 5, 2017
HER-2 SMASH
Celal Alandağ1, Ayşegül Öztürk2, Fatih Yulak3
1Department of Medical Oncology, Sivas Medicana Hospital, Sivas, Türkiye. dralandag@hotmail.com.
Purpose:
Human epidermal growth factor-2 (HER-2) targeted drugs are used in only HER-2 overexpressed cancers. However, only a small portion of these cancer types are HER-2 overexpressed. In this study, we aimed to upregulate HER-2 receptors in MCF-7 breast cancer and HT-29 colon cancer cell cultures, which these cells are not HER-2 upregulated in natural status.
Methods:
We used a 10-day non-cytotoxic lapatinib dose to upregulate HER-2 receptors. HER-2 levels of these cell lines were tested with ELISA and immunofluorescence tests before and after 10 days of lapatinib administration. After upregulation of HER-2, we administered trastuzumab, and T-DM1 to these cell lines to observe whether there is an increase in anticancer activity. We used a cell viability test to show the cytotoxicity of trastuzumab and T-DM1. Also, we used ELISA and immunofluorescence for HER-2 pathway proteins to understand the mechanism of increased anti-cancer activity.
Results:
We showed that administration of lapatinib for 10 days leads to overexpression of HER-2 receptors on both MCF-7 and HT-29 cells. A significant increase in the cytotoxicity of trastuzumab or T-DM1 was observed after 10 days of lapatinib administration.
Conclusion:
We named this method the smash method, which is the volleyball term. In volleyball, the ball is raised while low and quickly hits the ground again, just like we do with the HER-2 receptor. The smash method can switch HER-2 negative or HER-2 low tumors into HER-2 overexpressed, iatrogenically. Thus, we can use her2-targeted therapies in all cancer patients instead of a small portion.
Insights
Lapatinib treatment upregulates human epidermal growth factor-2 (HER-2) receptors in cancer cells, enhancing the effectiveness of HER-2 targeted therapies like trastuzumab and T-DM1. This novel "smash method" broadens treatment applicability for HER-2 low or negative tumors.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- HER-2 targeted therapies are effective only in a subset of cancers with HER-2 overexpression.
- Many cancer types, including breast and colon cancers, naturally exhibit low or absent HER-2 expression, limiting treatment options.
Purpose of the Study:
- To investigate the upregulation of human epidermal growth factor-2 (HER-2) receptors in HER-2 negative/low cancer cell lines (MCF-7 and HT-29).
- To evaluate the impact of lapatinib-induced HER-2 upregulation on the efficacy of HER-2 targeted therapies (trastuzumab, T-DM1).
Main Methods:
- Non-cytotoxic lapatinib doses were administered for 10 days to MCF-7 and HT-29 cell lines to induce HER-2 overexpression.
- HER-2 levels were quantified using ELISA and immunofluorescence assays before and after lapatinib treatment.
- The impact of trastuzumab and T-DM1 on cell viability was assessed, alongside analysis of HER-2 pathway proteins to elucidate mechanisms.
Main Results:
- Lapatinib administration for 10 days successfully induced significant HER-2 receptor overexpression in both MCF-7 and HT-29 cells.
- A notable increase in the anti-cancer activity and cytotoxicity of trastuzumab and T-DM1 was observed following lapatinib-induced HER-2 upregulation.
Conclusions:
- The developed 'smash method' effectively converts HER-2 negative or low tumors into HER-2 overexpressing ones, iatrogenically.
- This approach holds potential for expanding the patient population eligible for HER-2 targeted therapies, improving treatment outcomes across diverse cancer types.
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