Yibo Luo's research while affiliated with Medical University of Ohio at Toledo and other places

Simple Summary Cancer remains a debilitating disease and a worldwide health burden, and their treatment has been a forefront interest for researchers and clinicians for centuries. The search for novel approaches to selectively target certain proteins in just cancer cells, while sparing normal, healthy cells, has been the holy grail to limit side effects of treatments. This review aims to assess the potential of tBid, a pro-apoptotic mitochondrial protein found in normal and healthy cells, as a target for treating cancers. Cancer cells with tBid accumulation at mitochondria are “primed” for apoptosis, and, surprisingly, may be resistant to apoptosis owing to the association of tBid with antiapoptotic proteins. These cancer cells are more vulnerable to drugs that target these associations, with the possibility of limiting the use of chemo- or other cancer therapies. Abstract Effective cancer therapy with limited adverse effects is a major challenge in the medical field. This is especially complicated by the development of acquired chemoresistance. Understanding the mechanisms that underlie these processes remains a major effort in cancer research. In this review, we focus on the dual role that Bid protein plays in apoptotic cell death via the mitochondrial pathway, in oncogenesis and in cancer therapeutics. The BH3 domain in Bid and the anti-apoptotic mitochondrial proteins (Bcl-2, Bcl-XL, mitochondrial ATR) it associates with at the outer mitochondrial membrane provides us with a viable target in cancer therapy. We will discuss the roles of Bid, mitochondrial ATR, and other anti-apoptotic proteins in intrinsic apoptosis, exploring how their interaction sustains cellular viability despite the initiation of upstream death signals. The unexpected upregulation of this Bid protein in cancer cells can also be instrumental in explaining the mechanisms behind acquired chemoresistance. The stable protein associations at the mitochondria between tBid and anti-apoptotic mitochondrial ATR play a crucial role in maintaining the viability of cancer cells, suggesting a novel mechanism to induce cancer cell apoptosis by freeing tBid from the ATR associations at mitochondria.