Tumor initiation and progression rely on a subpopulation of self-renewing cancer stem cells. These cells promote new tumorigenic cells as well as play a major role in the growth and maintenance of cancer, leading to metastasis, therapy resistance, and tumor recurrence following treatment.
LEFTY1 is a member of the transforming growth factor beta (TGF-β) family. The LEFTY1 signaling pathway has been shown to promote long-term growth of immature cancerous mammary gland stem cells which has important implications for breast cancer. Preclinical studies showed that tumorigenic mammary cells expressed significantly higher levels of LEFTY1 compared to non-tumorigenic mammary cells.1 Inhibition of LEFTY in breast cancer models caused significant impairment of tumor progression or completely inhibited tumor growth altogether. Furthermore, review of two major cancer genome databases (The Cancer Genome Atlas and the Molecular Taxonomy of Breast Cancer International Consortium) showed that LEFTY1 was amplified in approximately 20% of human breast cancer samples across both datasets. These data support the potential for inhibitors against LEFTY1 to impact the treatment of breast and other types of cancers.
Tachyon has partnered with AbCellera Biologics Inc. to develop a therapeutic to target this previously unexplored mechanism by which LEFTY1 acts as a physiological driver of the long-term growth of tumor-initiating breast cancer stem cells. This therapeutic, called TACH204, is currently in discovery phase with plans to perform IND-enabling studies by 2H 2022.
1. Zabala, et al., LEFTY1 Is a Dual-SMAD Inhibitor that Promotes Mammary Progenitor Growth and Tumorigenesis. Cell Stem Cell . 2020.