Specifically, CPA4 modulates AKT phosphorylation by regulating the expression of the AKT phosphatase PP2A, while inhibition of the AKT signalling pathway leads to a decreased transcription and translation levels of CPA4. Our study reveals a novel mechanism of pyroptosis induced by HGS-ETR1/2, which may provide a crucial foundation for future investigations into cancer immunotherapy.
Collectively, our findings demonstrate that treatment with CPT in combination with Dox exerts synergistic antitumor effects through activation of the caspase cascade pathway, a mechanism that is partly dependent on the Dox-induced upregulation of death receptor 4 and death receptor 5. Therefore, CPT combined with Dox may be a feasible therapeutic strategy for the management of TNBC.
Certain clues of scientific evidence have provided encouraging results about efficacy of these agonistic antibodies (lexatumumab and mapatumumab) against bladder cancer cell lines. Therefore, multipronged approaches consisting of natural products, chemotherapeutics, and agonistic antibodies will realistically and mechanistically provide proof-of-concept for the translational potential of these combinatorial strategies in well-designed clinical trials.