Results of the First Phase I Clinical Trial of the Novel Ii-Key Hybrid Preventive HER-2/neu Peptide (AE37) Vaccine

2008 ◽  
Vol 26 (20) ◽  
pp. 3426-3433 ◽  
Author(s):  
Jarrod P. Holmes ◽  
Linda C. Benavides ◽  
Jeremy D. Gates ◽  
Mark G. Carmichael ◽  
Matthew T. Hueman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Peptide Vaccine ◽  
Delayed Type Hypersensitivity ◽  
Breast Cancer Patients ◽  
Gm Csf ◽  
Her 2 ◽  
Dose Reductions

Purpose HER-2/neu is overexpressed in breast cancer and is the source of immunogenic peptides. CD4+ T-helper peptides for HER-2/neu are being evaluated in vaccine trials. The addition of Ii-Key, a four–amino-acid LRMK modification, increases vaccine potency when compared with unmodified class II epitopes. We present the results of the first human phase I trial of the Ii-Key hybrid HER-2/neu peptide (AE37) vaccine in disease-free, node-negative breast cancer patients. Patients and Methods The dose escalation trial included five dose groups, to determine safety and optimal dose of the hybrid peptide (100 μg, 500 μg, 1,000 μg) and granulocyte-macrophage colony-stimulating factor (GM-CSF; range, 0 to 250 μg). In the event of significant local toxicity, GM-CSF (or peptide in absence of GM-CSF) was reduced by 50%. Immunologic response was monitored by delayed-type hypersensitivity and [3H]thymidine proliferative assays for both the hybrid AE37 (LRMK-positive HER-2/neu:776-790) and AE36 (unmodified HER-2/neu:776-790). Results All 15 patients completed the trial with no grade 3 to 5 toxicities. Dose reductions occurred in 47% of patients. In the second group (peptide, 500 μg; GM-CSF, 250 μg), all patients required dose reductions, prompting peptide-only inoculations in the third group. The vaccine induced dose-dependent immunologic responses in vitro and in vivo to AE37, as well as AE36. Conclusion The hybrid AE37 vaccine seems safe and well tolerated with minimal toxicity if properly dosed. AE37 is capable of eliciting HER-2/neu–specific immune responses, even without the use of an adjuvant. This trial represents the first human experience with the Ii-Key modification, and to our knowledge, AE37 is the first peptide vaccine to show potency in the absence of an immunoadjuvant.

Results from the first phase I clinical study of the novel Ii-Key/HER2/neu(776–790) hybrid peptide vaccine in patients with prostate cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3011-3011
Author(s):  
S. A. Perez ◽  
S. Bisias ◽  
N. L. Kallinteris ◽  
A. Ardavanis ◽  
K. G. Georgakopoulou ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Mhc Class Ii ◽  
Peptide Vaccine ◽  
Hormonal Treatment ◽  
Gm Csf ◽  
Additional Chemotherapy ◽  
Her 2

3011 Background: HER-2/neu(776–790) represents an immunogenic epitope from the HER-2/neu oncoprotein whose immunogenicity is highly potentiated upon linkage with the Ii-Key moiety (LRMK) from the MHC class II invariant chain. Herein, we present the results of the first phase I clinical trial of the Ii-Key/HER-2/neu(776–790) (AE37) vaccine in patients (pts) with prostate cancer. Methods: Androgen-dependent (AD) and androgen-independent (AI) pts with HER-2/neu+ (IHC: 1–3) prostate adenocarcinomas were eligible. Concomitant medication with bicatulamide and LHRH or docitaxel was allowed. All pts received 6 monthly vaccinations with the AE37 vaccine (500 μg of AE37 plus 125 μg of GM-CSF) administered in two doses intradermally 5cm apart in the same extremity for each vaccination cycle. Immunologic responses were measured monthly in vitro by the IFNγ-based ELISPOT assay using pts’ PBMC and in vivo at the beginning and end of immunizations using DTH. Local dermal reactions were also measured after each vaccination. Results: Eligible pts [AD (n=18), AI (n=10)] were at stages T1–3N0M0, GS: 3–7 (n=18); T1–3N+M0, GS: 6–7 (n=2); T1–3N0M+, GS: 6–9 (n=4) and T1–3N+M+, GS: 6–9 (n=4). All pts had standard treatment prior to vaccinations, including surgery (S) (n=9); hormonal treatment (HT) (n=4); S+HT (n=6); S+HT+radiotherapy (RT); (n=2); S+chemotherapy (CH) (n=2); HT+RT (n=2); CH (n=3) and S+HT+CH (n=2). During vaccinations, 11 pts were free of any treatment, while 5 pts who had progressive disease received additional chemotherapy; the remainder received HT alone or combined with RT. 25 pts completed all vaccinations. Toxicity and side effects beyond grade-2 were not observed. GM-CSF was reduced by 50% for subsequent vaccinations when a local reaction of 100mm or greater was observed. DTH reactions to the parent HER-2/neu(776–790) peptide were increased (compared to pre-vaccination) for all pts, while approximately half the pts responded with significantly increased IFNγ responses to AE37 and/or parent HER-2/neu(776–790) peptide in at least 2 sequential vaccination cycles. Conclusions: The AE37 vaccine is safe and well tolerated. AE37 is also capable of eliciting potent and specific immunologic responses in prostate cancer pts. [Table: see text]

An assessment of disease features and immune response in breast cancer patients that did not recur after receiving HER2 peptide, AE37 vaccine in a randomized phase II trial.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 625-625
Author(s):  
Diane F Hale ◽  
Sonia A. Perez ◽  
Timothy J Vreeland ◽  
Alfred F Trappey ◽  
Raetasha Sheavette Dabney ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Stimulation Index ◽  
Delayed Type Hypersensitivity ◽  
Her2 Status ◽  
Breast Cancer Patients ◽  
Clinical Recurrence ◽  
Node Positive

625 Background: In a phase I trial of AE37, the Ii-Key hybrid of HER2 derived peptide AE36 (776-790), administered with immunoadjuvant GMCSF demonstrated the vaccine to be safe and capable of stimulating CD4+helper T cells with HER2 specific anti-tumor activity. Here we present analysis of immune markers and patient feature that may impact recurrence from an ongoing prospective, randomized, single-blinded Phase IIb trial of AE37+GMCSF v GMCSF alone in adjuvant high risk breast cancer (BC) patients. Methods: After completion of standard therapy; disease-free, node positive or high risk node negative BC patients (pts) were randomized to receive either AE37+GMCSF or GMCSF in 6 monthly intradermal inoculations. Immunologic responses were measured using [3H]-thymidine incorporation assay (in vitro), delayed-type hypersensitivity (DTH) reactions (in vivo) and T regulatory cells (Tregs). Among those vaccinated recurrent pts (VR) are compared to non recurrent (VNR) pts. Results: We have vaccinated 109 pts with 8.3% recurrence rate at 2 year median follow up. VR v VNR were younger (44 v 50 yo p=0.11), had higher grade (67% v 44% p=0.32), more ER/PR- (44% v 38% p=0.75), larger tumors (89% v 50% p=0.06), and node positive (89% v 70% p=0.37). No difference for HER2 status (IHC 3+, 44% v 49% p=0.64). Both VR and VNR responded to vaccine though the mean DTH and proliferative stimulation index was approximately 10% less in VR pts (18 v 20 p=0.73; 1.96 v 2.2 p=0.77 respectively). The most predictive measure was change in Tregs with VR pts less likely to decrease their Tregs levels (50% v 76% p=0.17) after vacination and more likely experience increased Tregs (17% v 8% p=0.48). A decrease in Tregs had an inverse trend towards recurrence (p=0.17). Conclusions: Preliminarily, it appears most pts immunologically respond to vaccine though slightly less for VR in most assays. The changes of Tregs appear to correlate best with disease recurrence. Whether this reflects an association with disease status or a failure of the vaccine is yet to be seen. These levels may become important in predicting risk for clinical recurrence in future vaccine trials.

Safety and long-term maintenance of anti-HER2 immunity following booster inoculations of the E75 breast cancer vaccine.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2529-2529
Author(s):  
Raetasha Sheavette Dabney ◽  
Diane F Hale ◽  
Timothy J Vreeland ◽  
Guy T. Clifton ◽  
Alan K. Sears ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Vaccine ◽  
Peptide Vaccine ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Recurrence Rates ◽  
Specific Immunity

2529 Background: We have completed accrual and are in the follow up portion of phase I/II clinical trials evaluating the E75 HER2 peptide vaccine. E75 has been proven safe, capable of stimulating HER2 immunity, and effective in decreasing breast cancer recurrence rates. During the conduct of this trial, it was noted that E75-specific immunity waned after the Primary Vaccine Series (PVS) which corresponded with late recurrences. To maintain long-term immunity, a voluntary booster program was started. Here we present analysis of the booster inoculations. Methods: The trial enrolled node-positive or high-risk, node-negative breast cancer patients (pts) with tumors expressing any level of HER2 (IHC 1-3+). HLA-A2/A3+ pts comprised the vaccine group (VG), HLA-A2/A3- pts were followed as the control group (CG). The VG received 4-6 monthly inoculations of E75+GM-CSF. Volunteer booster program pts (BG) received inoculations every 6 months after the PVS. Pts were monitored for toxicities, in vivo responses by local reactions (LR) and DTH, and in vitro responses measured by enumeration of E75 specific cytotoxic T lymphocytes. Results: 53 pts received at least 1 booster, 34 received 2, 24 three, 20 four, 12 five, and 8 at least 6. 24% of pts had no local toxicity, 73% Grade 1 (G1), 3% G2. 74% had no systemic toxicity, 35% G1, 1% G2. LRs increased significantly from the initial vaccine (R1) during PVS to each booster (B) (R1: 59.5±3.1 v B1: 89.2±3.3, p<0.001; v B2: 95.15±5, p<0.001; v B3: 86.63±5.5, p<0.001; v B4: 83.26±4.6, p=<0.001; v B5: 80.67±6.7, p=0.006; v B6: 78.75±9.4, p=0.04). Dimer values increased from the end of PVS to each post-booster value (pre B1:1.29±0.25 v post B1: 1.46±0.38; post B2: 1.41±0.4; post B3: 1.84±0.35; post B4: 2.23±0.4; post B5:1.94±0.31; post B6: 2.73±0.09, p=0.02). At median 60 months, the recurrence rate for BG was 3.8% vs 18.9% in the CG (p=0.01). Conclusions: Booster inoculations are well-tolerated and appear to assist in the maintenance of long term peptide-specific immunity. Boosted pts have improved recurrence rates. Based on the success of this program, we have incorporated the practice of booster inoculations in our current cancer vaccine trials.

Biomarker correlation to clinical response in phase I/II trials of the adjuvant breast cancer vaccine neuvax (nelipepimut-S or E75).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS3126-TPS3126
Author(s):  
John S. Berry ◽  
Alfred F Trappey ◽  
Alan K. Sears ◽  
Timothy J Vreeland ◽  
Guy T. Clifton ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Peptide Vaccine ◽  
Clonal Expansion ◽  
Mean Difference ◽  
Control Group ◽  
Breast Cancer Patients ◽  
Clinical Recurrence ◽  
The Mean

TPS3126 Background: We completed phase I/II clinical trials with NeuVax (nelipepimut-S), a HLA-A2/A3-restricted, HER2-derived peptide vaccine. The vaccine was administered in the adjuvant setting to prevent recurrence in breast cancer patients rendered disease-free with standard-of-care therapy. Here, we examine the relationship between in vitro immunologic response (IR) and clinical recurrence (CR) after 5-year follow-up. Methods: The phase I/II trials were performed as dose-escalation/schedule-optimization trials enrolling node positive and high-risk, node-negative patients (pts) with tumors expressing any level of HER2 (IHC 1+,2+,or 3+). HLA-A2/A3+ pts were enrolled in the vaccine group (VG) while HLA-A2/A3- pts were followed prospectively as an untreated control group (CG). The VG was given 4-6 monthly intradermal inoculations of nelipepimut-S+GMCSF (immunoadjuvant) during the primary vaccine series (PVS). In vitro IR was assessed for E75-specific, cytotoxic T lymphocyte clonal expansion by HLA-A2:IgG dimer assay and expressed as mean dimer index (mdi) at baseline, after PVS (R6), and six months after the PVS. HER2 under-expression was defined as an IHC 1/2, and a FISH < 2.2. VG and CG pts were followed for CR over 60 months. P-values were calculated using the Fisher’s exact test. Results: Of the 195 pts enrolled, 8 withdrew, leaving 187 evaluable pts; 108 in the VG and 79 in the CG. R6 dimer assays were available for 86 pts in the VG. The mean R6 dimer in the VG is 0.63 mdi+.08. Of the 30 pts with an R6 dimer above the mean, only one recurred, compared to eight of the 56 below the mean (p=.09). The difference between baseline and maximum mdi was available in 56 HER2 under-expressing VG pts. Of the 26 pts above the mean difference (1.08 mdi +.17), one recurred, compared to six CR in the 30 pts below the mean (p=.06). There were no CR in pts with HER2 under expression with a mean difference ranked in the top third. Conclusions: In prospective, completed phase I/II trials of NeuVax (nelipepimut-S), patients who exhibit robust in vitro IR have lower recurrence rates. This finding suggests that nelipepimut-specific CTL clonal expansion is a valid biomarker for CR in pts treated with NeuVax. Clinical trial information: NCT00841399.

Selective inhibition of ADAM metalloproteases blocks HER-2 extracellular domain (ECD) cleavage and potentiates the anti-tumor effects of trastuzumab

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13021-13021 ◽  
Author(s):  
P. Scherle ◽  
X. Liu ◽  
J. Li ◽  
J. Fridman ◽  
Y. Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Cancer Patients ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Therapeutic Intervention ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Her 2

13021 Background: HER-2, a member of ErbB family of receptor tyrosine kinases, is an important regulator of cell proliferation and survival, and is a clinically validated target of therapeutic intervention in HER-2 positive metastatic breast cancer patients. In HER-2 overexpressing cells, the extracellular domain (ECD) is frequently cleaved, rendering the remaining transmembrane portion of HER-2 (p95) constitutively active. The presence of both serum ECD and cellular p95 protein have been linked to poor clinical outcome as well as reduced effectiveness of some therapeutic treatments, suggesting that signaling via p95 is clinically relevant and may represent an attractive target for therapeutic intervention. Methods: Through medicinal chemistry efforts, we have identified a series of potent, selective small molecule inhibitors of ADAM metalloproteases, exemplified here by INCB7839. These compounds were tested both in vitro and in vivo for inhibition of HER-2 ECD cleavage and anti-tumor activity in the HER-2 overexpressing BT-474 cell line. Inhibition of circulating HER-2 ECD levels was monitored in a phase I multiple dose escalation study in healthy volunteers. Results: We demonstrate that these inhibitors effectively blocked HER-2 cleavage in HER-2 overexpressing human breast cancer cell lines. When used in combination, INCB7839 dramatically enhanced the antiproliferative activity of suboptimal doses of the anti-HER-2 antibody, trastuzumab, in HER-2 overexpressing/shedding breast cancer cell lines, accompanied by reduced ERK and AKT phosphorylation. Consistent with these in vitro data, INCB7839 reduced serum ECD levels in tumor-bearing mice and enhanced the antitumor effect of trastuzumab in a xenograft tumor model derived from the HER-2 overexpressing BT-474 breast cancer cell line. In a phase I clinical trial, INCB7839 demonstrated a dose-dependent decrease in the circulating levels of HER-2 ECD present in healthy volunteers. Conclusions: Collectively, these findings suggest that blocking HER-2 cleavage with selective ADAM inhibitors, especially in combination with anti-HER-2 antibody therapy, may represent a novel approach for treating HER-2 overexpressing breast cancer patients. [Table: see text]

Immunologic responses in triple-negative breast cancer patients in a randomized phase IIb trial of nelipepimut-S plus trastuzumab versus trastuzumab alone to prevent recurrence.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 556-556
Author(s):  
Jessica Campf ◽  
Guy T. Clifton ◽  
Diane F. Hale ◽  
Timothy J. Vreeland ◽  
Annelies Hickerson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Ex Vivo ◽  
Delayed Type Hypersensitivity ◽  
Breast Cancer Patients ◽  
Gm Csf ◽  
Macrophage Colony Stimulating Factor ◽  
Macrophage Colony ◽  
Relationship Of

556 Background: Breast cancer (BC) patients (pts) expressing low levels of HER2 by (immunohistochemistry (IHC) 1-2+) are not eligible for trastuzumab (Tz). However, in a randomized phase 2b trial, triple negative BC (TNBC) pts demonstrated a significantly better DFS with nelipepimut-S (NPS) + Tz vs Tz alone. Here, we assess the ex vivo and in vivo immune responses (IR) in both arms. Methods: Disease-free pts (n = 275) with HER2 IHC 1-2+, non-amplified BC who were node positive and/or had TNBC were randomized 1:1 to granulocyte-macrophage-colony stimulating factor (GM-CSF) or NPS+GM-CSF. ±NPS was given every 3 weeks x 6 followed by 4 boosters every 6 months (mo). All pts received Tz concurrently for 1 year per label regimen and were followed for recurrence. IR were evaluated ex vivo by clonal expansion of NPS-specific cytotoxic T lymphocytes (CTL) by dextramer-staining/flow cytometry at time points over 3 years. In vivo IR were assessed by delayed type hypersensitivity (DTH) reactions periodically. Results: The trial enrolled 97 TNBC pts; 60 had 4 timepoints available for analysis (37 NPS + Tz pts; 23 Tz pts). The NPS+Tz group exhibited increases in CTL frequencies vs baseline: 208%, 303%, 379% at 18, 24 and 30 mo, respectively. NPS+Tz pts’ mean CTL frequencies increased from 0.029 ±0.001% at baseline to 0.112±0.026% at 30 mo (p = 0.01) compared to Tz pts who were 0.027 ±0.001% at baseline and 0.057 ±0.016% at 30 mo (p = 0.71). Only 4 NPS+Tz pts recurred as compared to 13 in the Tz arm. While limited by low numbers, recurrent NPS + Tz pt did not mount an IR by ex vivo assessment (range: 0.0 - 0.026%) or by DTH (all measurements: 0 mm), while non-recurrent pts mounted both clonal CTL expansion (range: 0.000- 0.33%) and enhanced DTH (range: 0.0- 80.5mm). Conclusions: NPS+Tz combination is more efficacious in generating time-dependent antigen (NPS)-specific CTL by both ex vivo and in vivo measures vs Tz. Based on these preliminary data, it appears that both ex vivo and in vivo IR to NPS were attenuated in pts with TNBC recurrence. Further analysis of read-outs from these assays to validate the relationship of IRs to clinical effect seen with NPS+Tz in TNBC pts is underway. Clinical trial information: NCT02297698.

Randomized phase II clinical trial of the anti-HER2 (GP2) vaccine to prevent recurrence in high-risk breast cancer patients: A planned interim analysis.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3005-3005 ◽  
Author(s):  
Francois Trappey ◽  
John S. Berry ◽  
Timothy J Vreeland ◽  
Diane F. Hale ◽  
Alan K. Sears ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Cancer Patients ◽  
Phase Ii ◽  
Interim Analysis ◽  
Peptide Vaccine ◽  
Delayed Type Hypersensitivity ◽  
Breast Cancer Patients ◽  
Gm Csf

3005 Background: A prospective, randomized, multi-center, placebo-controlled, single-blinded, phase II trial was designed to evaluate the safety and clinical efficacy of GP2, a HER2-derived peptide vaccine, in breast cancer patients. Methods: Clinically disease-free, node-positive or high-risk node-negative patients (pts) with any level of HER2 expression were enrolled after standard of care therapy. HLA-A2+ pts were randomized to receive GP2 + GM-CSF (VG) or GM-CSF alone (CG). HLA A2- controls from a parallel arm of the study were also eligible for evaluation, the extended CG (ECG). Pts receive 6 monthly intradermal inoculations (R0-R6) during the primary vaccine series followed by four boosters every 6 mos. Immune responses (IR) were measured by delayed type hypersensitivity (DTH) at R0 and R6. This planned interim analysis was performed at 24 months median follow-up. Results: We have currently enrolled 172 pts (46, VG; 43, CG; 83 extended CG). There are no differences between groups with respect to age, rate of node positivity, tumor grade, tumor size, ER/PR status, and HER2 over-expression (all p > 0.05). Maximum local toxicity (tox) was similar between the two groups (grade (Gr) 1 and 2: VG 93%, CG 98%; Gr 3: VG 2%, CG 1%). Maximum systemic tox was also similar between the groups (Gr 1 and 2: VG 91%, CG 85%). No Gr 3 systemic tox has been reported. The most frequent systemic reactions are fatigue, headache, and myalgias. IR to GP2 has been robust. DTH is increased from R0 to R6 in the VG (3.0±0.98 to 21.5±4.04 mm, p < 0.01) vs. the smaller increase in CG (2.6±0.89 to 6.0±1.6 mm, p = 0.01). VG DTH at R6 is significantly higher than the CG (21.5 vs 6.0 mm, p < 0.01). The recurrence rate (RR) is decreased in the VG vs CG (4.3% vs. 11.6%, p = 0.41) and VG vs ECG (4.3% vs 9.5%, p = 0.41). In pts with HER2-overexpressing (IHC3+ or FISH+) tumors, the RR is decreased in the VG (0% vs 5% CG, p = 0.28). For TNBC (HER2 low, ER/PR-) pts, the RR is reduced in the VG vs ECG (0% vs 10.6%, p = 0.251). Conclusions: The GP2 vaccine is safe and the minimal toxicity is comparable between the VG and CG, suggesting that it is due to GM-CSF. Robust in vivo immune response has correlated with a >50% reduction in breast cancer recurrences in the VG. Clinical trial information: NCT00524277.

Targeting PKM2 promotes chemosensitivity of breast cancer cells in vitro and in vivo

2021 ◽  
pp. 1-10
Author(s):  
Yu Wang ◽  
Han Zhao ◽  
Ping Zhao ◽  
Xingang Wang
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Poor Prognosis ◽  
Breast Cancer Cells ◽  
Breast Cancer Patients ◽  
Cancer Tissues

BACKGROUND: Pyruvate kinase M2 (PKM2) was overexpressed in many cancers, and high PKM2 expression was related with poor prognosis and chemoresistance. OBJECTIVE: We investigated the expression of PKM2 in breast cancer and analyzed the relation of PKM2 expression with chemotherapy resistance to the neoadjuvant chemotherapy (NAC). We also investigated whether PKM2 could reverse chemoresistance in breast cancer cells in vitro and in vivo. METHODS: Immunohistochemistry (IHC) was performed in 130 surgical resected breast cancer tissues. 78 core needle biopsies were collected from breast cancer patients before neoadjuvant chemotherapy. The relation of PKM2 expression and multi-drug resistance to NAC was compared. The effect of PKM2 silencing or overexpression on Doxorubicin (DOX) sensitivity in the MCF-7 cells in vitro and in vivo was compared. RESULTS: PKM2 was intensively expressed in breast cancer tissues compared to adjacent normal tissues. In addition, high expression of PKM2 was associated with poor prognosis in breast cancer patients. The NAC patients with high PKM2 expression had short survival. PKM2 was an independent prognostic predictor for surgical resected breast cancer and NAC patients. High PKM2 expression was correlated with neoadjuvant treatment resistance. High PKM2 expression significantly distinguished chemoresistant patients from chemosensitive patients. In vitro and in vivo knockdown of PKM2 expression decreases the resistance to DOX in breast cancer cells in vitro and tumors in vivo. CONCLUSION: PKM2 expression was associated with chemoresistance of breast cancers, and could be used to predict the chemosensitivity. Furthermore, targeting PKM2 could reverse chemoresistance, which provides an effective treatment methods for patients with breast cancer.

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