Tumor suppressors are molecules that mainly function as inhibitors of the proliferation or survival of tumor cells, including proteins encoded by tumor suppressor genes (TSGs, also known as anti-oncogenes) and microRNAs. Inhibition of tumor suppressors leads to tumor development by repressing negative regulatory proteins. Generally, tumor suppressors downregulate the same cell regulatory pathways triggered by oncogene products. Although tumor suppressors share a similar main function, their specific action mechanisms vary from each other.
Tumor suppressors are essential in the regulation of many biological activities. According to their roles in cell proliferation, cell-cycle stages, DNA damage repair, and multiple signaling pathways, tumor suppressors can be broadly classified into the following types:
Considering the diversity and importance of roles that tumor suppressors take in various biological functions, they have been studied extensively and applied as therapeutic targets. During the past decades, numerous promising strategies directed targeting tumor suppressors, or the related signaling pathways, have emerged. Here we list some representative examples of tumor suppressors and the advances in antibody development aiming at them.
The TSG TP53 is the most frequently mutated gene in human tumors, and the encoded p53 protein functions mainly as a transcription factor and a genome guardian, participating in the regulation of a broad range of pathways, including DNA damage repair, cell apoptosis, cell cycle arrest, metabolism, and autophagy, and involved in the responses to stress conditions, making its pathway attract much attention as a therapeutic target. For example, p53 is negatively regulated by its main regulator MDM2/MDMX, which is a promising target for therapeutic strategies. There are a large number of MDM2-p53 inhibitors undergoing different stages of clinical trials currently.
Fig.1 The signaling pathway of p53.1
BRCA is a classical tumor suppressor, and its deficiency or mutation increases the risks of multiple cancers, including breast, pancreatic, ovarian, and prostate cancer. The BRCA pathway is associated with DNA inter-strand cross-links repair, in which there are molecules involved, including BRCA1/2, PARP, PALB2, CHK1, FANCC, FANCG, etc.
MicroRNAs post-transcriptionally regulate genes by complementarity pairing, and are widely reported to act as tumor suppressors or oncomiR (depending on cell types) in cancers, exerting functions in the immune system, inflammation, cell proliferation and growth, angiogenesis, apoptosis, repair of DNA damage, etc. Tumor therapy using miRNAs has gained extensive attention, aiming to maintain the expression of tumor-suppressing miRNAs and inhibit the oncogenes that they target. There have been numerous patents and clinical trials based on the strategy published during these years, exhibiting encouraging results and indicating that targeting miRNA and related genes can be utilized to guide an effective way to cancer treatment.
As a pioneer in antibody research and development, Amerigo Scientific has gained rich knowledge and resources in targeting various tumor suppressors and their pathways. We are proud to introduce our antibody products for various applications to our esteemed clients around the world, please feel free to for more information.
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