Abstract
Triple negative breast cancer (TNBC), is defined as a type of tumor lacking the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). The ER, PR and HER2 are usually the molecular therapeutic targets for breast cancers, but they are ineffective for TNBC because of their negative expressions, so chemotherapy is currently the main treatment strategy in TNBC. However, drug resistance remains a major impediment to TNBC chemotherapeutic treatment. Recently, the protein phosphatase 2A (PP2A) has been found to regulate the phosphorylation of some substrates involved in the relevant target of TNBC, such as cell cycle control, DNA damage responses, epidermal growth factor receptor, immune modulation and cell death resistance, which may be the effective therapeutic strategies or influence drug sensitivity to TNBCs. Furthermore, PP2A has also been found that could induce ER re-expression in ER-negative breast cancer cells, and which suggests PP2A could promote the sensitivity of tamoxifen to TNBCs as a resistance reversal agent. In this review, we will summarize the potential therapeutic value of PP2A as the main node in developing targeting agents, disrupting resistance or restoring drug sensitivity in TNBC.
Highlights
Breast cancer is the most frequent cancer and the second leading cause of cancer-related mortality among women worldwide [1,2]
Triple-negative breast cancer (TNBC), which is defined by the lack of expression of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), is the most fatal subtype of breast cancer and is associated with relatively poorer outcomes compared with other breast cancer subtypes [3,4,5,6]
This novel mechanism of PD-L1 regulation was mainly mediated by the influence of HDAC6 over the recruitment and activation of STAT3. Their data clearly demonstrated that a possible explanation for the impaired phosphorylation of STAT3 in the absence of HDAC6 could be originated by the enhanced interaction of phosphatase 2A (PP2A) with STAT3, which in turn could facilitate the dephosphorylation of STAT3-mediated by. These findings reveal the requirement for proper balance of PP2A activity in immune modulation through multiple regulatory mechanisms, including cytotoxic T-lymphocyte antigen 4 (CTLA-4) and PD-1, and provide a key pre-clinical rationale and justification to further study PP2A regulators as potential immuno-modulatory agents in TNBCs
Summary
Breast cancer is the most frequent cancer and the second leading cause of cancer-related mortality among women worldwide [1,2]. 2 ofof 16 novel targets have emerged [15,16,17,18], which have great potential for drug sensitivity and therapeutic clinical response and survival after neoadjuvant chemotherapy suggest that different subset of TNBC development for TNBC. Phosphoprotein phosphatase 2A (PP2A), a major serine/threonine phosphatase, appears to be with increased understanding of TNBC biology, a number of novel targets have emerged critically involved in cellular growth control and potentially in the development of cancer through [15,16,17,18], which have great potential for drug sensitivity and therapeutic development for TNBC. PP2A the andefficacy its interactions with associated signaling pathways the can drug help us to shed light on its potential values as a novel strategy to enhance the efficacy of chemotherapy, as well as to overcome
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