Antibody targeting two pathways critical for cancer growth may be an effective treatment for cancer

A population of cells found in tumors — cancer stem cells (CSCs) — can both self-renew by dividing and give rise to many cell types that constitute the tumour. These cells are considered the driving force of tumorigenesis and the seeds of metastases. There is a concept that traditional radiotherapy and chemotherapy kill only non-CSC cancer cells while CSCs can resist the effect of these treatments.

According to a paper appearing in Science Translational Medicine, an antibody called CT16 could not only reduce the size of tumors but also act on CSCs. The antibody seems to block both the epidermal growth factor receptor (EGFR) and Notch pathways, both of which are involved in cancer cell growth.

Researchers who participated in the study include Shi Hu, Tian Li, Qingning Yuan, Feifei Wang, Gaojian Lv, Yuanyuan Lv, Xiaoyan Fan, Yafeng Shen, Fangxing Lin, Ying Tang, Xuting Ye, Yongji Yang and Changhai Lei from the Second Military Medical University, and Wenyan Fu from Fudan University.

EGFR is a drug target for many cancers. However, over time tumors acquire resistance to drugs targeting EGFR. One thing that leads to this resistance is an increased in the number of CSCs induced by the Notch pathway. To prevent the development of resistantce, the researchers in this study developed an antibody called CT16 that targets both EGFR and Notch.

CT16 was tested in mouse models of non-samll cell lung cancer. For tumors that were already resistant to EGFR inhibitors, CT16 had limited effects. In contrast, for other cases of tumors, CT16 was good at killing cancer cells — it was more efficarious compared to antibodies that only targetted EGFR or Norch. The results indicated that drugs targeting both EGFR or Norch is unable to overcome established acquired resistance but can effectively delay or prevent acquired resistance to EGFR inhibitors.

Furthermore, a combination of CT16 and radiotherapy had a larger antitumor effect than the combination of radiotherapy with EGFR inhibitors or tarextumab. Collectively, the study suggest that “a combined blockade of EGFR and Notch signaling to augment the response to radiation.” Cusabio offers HRP conjugated antibody.

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