Study finds that palbociclib and MLN0128 are co-anti-cancer active for TNBC

triple-negative breast cancer (TNBC) accounts for about 13-22% of breast cancer, so far, no targeted treatment for TNBC has been approvedrecently, published in Breast Cancer Research and Treatment, Takuro et alexplored the combined effects of Palbociclib and MLN0128 in estrogen receptor (ER)-negative breast canceron Palbociclib
Palbociclib is an approved cell cycle protein-dependent kinase (CDK) 4/6 inhibitor used to treat PATIENTs with ER-positive and HER2-negative breast cancerTakuro et alexplored the combination of palbociclib and rapamycin kinase inhibitor MLN0128 dual mammalian targets in the estrogen receptor (ER) negative breast cancer in vitro and in vitroThe authors studied the combination effect of palbociclib and MLN0128 by MTT determination and colony formation, and expressed pRb's MB231 and MB453 cell lines for control, single-drug or double-drug combination continuing treatment, and compared with the control group or single-drug group treatment, the combination of palbociclib and MLN0128 significantly inhibited the formation of two cell strainsAccording to Herrea-Abreu et al., CDK4/6 inhibitors increased the expression level of cyclin D1, and the combination of CDK4/6 inhibitors and PI3K inhibitors reduced cyclin D1The authors assessed the effects of a combination of single and two drugs on cyclin D1 expressionThere was also a slight increase in the expression of cell cycle protein E1 after the single palbociclib treatmenthowever, compared to cells treated with palbociclib alone, the combination of MLN0128 and the(http:// drug(http://) of the papopocib
drug reduced the level of cyclin E1 protein in both cell lines and also reduced cyclin E1 mRNA levelsIn addition, the use of palbociclib alone and combination of drugs can inhibit cyclin E2, which may also reflect g1 block 　　The authors used a pRb TNBC patient-derived xenotransplantation (PDX) model to assess the effects of the combination in the body The COH_GS6 tumors expressed with the highest phosphorylation pRb in the experiment, after 6 consecutive days of combination of Palbociclib, MLN0128 and Palbociclib and MLN0128, tumor growth as shown in Figure 2b-d, showed that Palbolib and MLN0128 co-effects can significantly inhibit tumor growth The authors analyze
the tumor growth inhibition mechanism from the protein imprint and ICH (http:// and through ICH analysis, the value of ki67 used in combination was significantly reduced compared with control and single-drug therapy, further confirming from the body that the combination of palbocic and MLN0128 has a synergistic inhibition effect on the growth of TNBC tumors expressed in the body prb the same, the same results were obtained from the results of the protein printing and dyeing test (http:// This conclusion is the same as in vitro studies In TNBC PDX, which expresses pRb, combination therapy significantly inhibited tumor growth compared to control or single therapy In addition, combination therapy significantly reduced the number of Ki67-positive cells 　　The authors found that both palbociclib and MLN0128 had synergistic anti-cancer activity in both pRb-ER-negative cell lines and TNBC PDX models, providing new targeted therapy for TNBC patients, and that this combination of treatments was worth further study in clinical settings