An immunological signature to predict outcome in patients with triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE185507 | GEO | 2022/09/20
REPOSITORIES: GEO
Similar Datasets
Project description:Optimal cytoreduction to no residual disease (R0) correlates with improved disease outcome in the management of high-grade serous ovarian cancer (HGSOC) patients. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) offers an alternate approach to management of HGSOC patients to achieve complete resection. This study assessed proteomic alterations in matched, chemotherapy naïve and NACT-treated patients tumors obtained from HGSOC patients with suboptimal (R1) versus optimal (R0) debulking at IDS. We describe distinct proteome profiles in pre- and post-NACT HGSOC tumors correlating with residual disease status providing prognostic biomarkers for residual disease at IDS as well as candidate proteins associated with NACT resistance warranting further pre-clinical investigation.
2022-10-05 | PXD031929 | Pride
Project description:In this study, we analyzed the differential spatial transcriptome of Triple-Negative Breast Cancer (TNBC) patients who responded in an opposite manner to neoadjuvant chemotherapy (NACT): we compared responders displaying pathological complete response (pCR) with no-responders who showed disease progression during therapy. Diagnostic TruCut biopsies were analyzed using the GeoMx Cancer Transcriptome Atlas (Nanostring).
2023-10-12 | E-MTAB-13069 | biostudies-arrayexpress
Project description:Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study We used gene expression data of TNBC patients with residual disease and different prognosis to molecularly define the clinically relevant subgroups, and developed a 7-gene prognostic signature for chemoresistant TNBCs
2013-01-15 | E-GEOD-43502 | biostudies-arrayexpress
Project description:Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer, with approximately 50% of patients having residual disease after neoadjuvant chemotherapy (NACT) and worse prognosis with higher residual cancer burden (RCB). Patient-derived xenograft (PDX) models of breast cancer are an effective discovery platform and tool for preclinical pharmacologic testing and biomarker identification. There is a need for PDX models encompassing the heterogeneity of TNBC both pre- and post- therapy and for identifying clinical and molecular features of patient’s tumors that are associated with success in establishing these models. Using fine-needle aspirates (FNAs), we established orthotopic PDX models of TNBC from the primary breast tumors of patients prior to and following neoadjuvant systemic therapy while enrolled in the ARTEMIS trial (NCT02276443). ARTEMIS is a prospective neoadjuvant clinical trial for women with primary TNBC who are treated with four cycles of Adriamycin combined with cyclophosphamide (AC) followed by taxane +/- different experimental therapies. Serial biopsies were obtained from patients prior to treatment (pre-therapy), from poorly responsive disease after four cycles of AC (mid-NACT), and in cases of AC-resistance, after a three-month course of different experimental therapies and/or additional chemotherapy (post-NACT). Our study cohort includes a total of 269 FNA biopsies from 217 women, generating a total of 62 successful PDX models (overall success-rate = 23%). This cohort includes five serial pre- and mid-NACT PDX pairs, as well as one serial pre-, mid-, post-NACT triplet. Success of PDX engraftment was generally higher from cancers that proved to be treatment-resistant: whether poor response to AC determined by ultrasound measurements mid-NACT (p=0.063), RCB II/III status after NACT (p=0.046), or metastatic relapse within two years of surgery (p=0.008). TNBC molecular subtype determined from gene expression microarrays of pre-NACT tumor revealed no significant association with PDX engraftment rate (p=0.877). Finally, we developed a statistical model predictive of PDX engraftment using percent Ki67 positive cells in the patient’s diagnostic biopsy, positive lymph node status at diagnosis, and low volumetric reduction of the patient’s tumor following AC treatment. This novel bank of 62 PDX models of TNBC provides a valuable resource for biomarker discovery and preclinical therapeutic trials aimed at improving neoadjuvant response rates for patients with TNBC.
2023-01-12 | GSE216333 | GEO
Project description:Summary: There is a need for biomarkers predictive of response to neoadjuvant chemotherapy (NACT) in triple-negative breast cancer (TNBC). We previously obtained evidence that a polyamine signature in the blood is associated with TNBC development and progression. In this study, we evaluated whether plasma polyamines and other metabolites may identify TNBC patients who are unlikely to respond to NACT. Pre-treatment plasma levels of acetylated polyamines were elevated in TNBC patients that had moderate to extensive tumor burden (RCB-II/III) following NACT compared to those that achieved a complete pathological response (pCR/RCB-0) or had minimal residual disease (RCB-I). We further applied artificial intelligence to comprehensive metabolic profiles to identify additional metabolites associated with treatment response. A deep learning model (DLM) consisting of two polyamines as well as nine additional metabolites was developed for improved prediction of RCB-II/III. The DLM has potential clinical value for identifying TNBC patients who are unlikely to respond to NACT and who may benefit from other treatment modalities.
2022-05-26 | ST002235 | MetabolomicsWorkbench
Project description:Triple-negative breast cancer (TNBC) patients with residual disease after neoadjuvant chemotherapy generally have worse outcome; however, some patients with residual tumor after neoadjuvant chemotherapy do not relapse. We hypothesize that there are subgroups of chemoresistant TNBC patients with different prognosis. In this study, 25 chemoresistant samples from 47 neoadjuvant chemotherapy-treated TNBC (The Methodist Hospital) are chosen for study
2013-01-15 | GSE43502 | GEO
Project description:Tongue squamous cell carcinoma is characterised by poor prognosis and high metastatic events. Patients with unresectable tumors are benefiting from neoadjuvant chemotherapy (NACT) which surgical resection, and controls distant metastasis, and locoregional recurrence. However, resistance to NACT limit the success of the treatment regimen. In this study, we investigated the altered proteome and phosphoproteome of NACT resistant and sensitive cohort using Mass spectrometry-based proteomics. We carried out proteomic as well as phosphoproteomic analysis of treatment naïve tongue cancer patients whose response to NACT is recorded. Proteomic analysis revealed distinct protein expression between the responders and non-responders. The Phosphoproteomic analysis revealed kinases and the pathways associated with NACT resistance in tongue cancer.
2023-03-11 | PXD037356 | Pride
Project description:We explore the potential of immune-associated expression profiles in a series of Epithelial Ovarian Cancer (EOC) patients undergoing neoadjuvant chemotherapy (NACT), comparing primary lesions before patients underwent carboplatin/paclitaxel-based NACT (so-called ´biopsy samples´) and interval debulking surgery (IDS) samples from residual lesions after treatment with chemotherapy (so-called ´surgery samples´).
2022-01-27 | GSE181597 | GEO
Project description:Non–small-cell lung cancer (NSCLC) is the leading cause of cancer deaths worldwide due to late diagnosis and lack of effective therapies to treat metastatic disease. About one third of NSCLC patients present at diagnosis with locally advanced cancer (stage IIIA) which metastasizes ipsilateral mediastinal or subcarinal lymph nodes (N2). Neoadjuvant chemotherapy (NACT) followed by surgery is the treatment of choice for resectable N2 disease. However, the majority of patients do not respond to NACT and show persistent lymph nodal metastases and an adverse outcome. Our scant knowledge of the molecular biology of lymph node metastases (LNmets) represents a major obstacle to develop more effective therapies. Here, we investigated gene expression profile (coding and non-coding) of LNmets collected by endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) and mediastinoscopy, in two cohorts of stage IIIA patients before NACT (N=70). We discovered a microRNA expression signature in LNmets predictive of NACT response of N2 patients. Importantly, we unveiled a miR-455-5p/PD-L1 regulatory axis which drives chemotherapy resistance and impact T cell viability in NSCLC. Our data suggests the relevance of LNmets molecular profiling to predict response to NACT likewise presents strong evidences of a miRNA-based mechanism which functionally links chemotherapy response with PD-L1 regulation.
2022-12-31 | GSE193707 | GEO
Project description:Triple negative breast cancer (TNBC) accounts for 15-20% of breast cancer cases in the United States. Systemic neoadjuvant chemotherapy (NACT), with or without immunotherapy, is the current standard of care for patients with early-stage TNBC. However, up to 70% of TNBC patients have significant residual disease once NACT is completed, which is associated with a high risk of developing recurrence within two to three years of surgical resection. To identify targetable vulnerabilities in chemoresistant TNBC, we generated longitudinal patient-derived xenograft (PDX) models from TNBC tumors before and after patients received NACT. We then compiled transcriptomes and drug response profiles for all models. Transcriptomic analysis identified the enrichment of aberrant protein homeostasis pathways in models from post-NACT tumors relative to pre-NACT tumors. This observation correlated with increased sensitivity in vitro to inhibitors targeting the proteasome, heat shock proteins, and neddylation pathways. Pevonedistat, a drug annotated as a NEDD8-activating enzyme (NAE) inhibitor, was prioritized for validation in vivo and demonstrated efficacy as a single agent in multiple PDX models of TNBC. Pharmacotranscriptomic analysis identified a pathway-level correlation between pevonedistat activity and post-translational modification (PTM) machinery, particularly involving neddylation and sumoylation targets. Elevated levels of both NEDD8 and SUMO1 were observed in models exhibiting a favorable response to pevonedistat compared to those with a less favorable response in vivo. Moreover, a correlation emerged between the expression of neddylation-regulated pathways and tumor response to pevonedistat, indicating that targeting these PTM pathways may prove effective in combating chemoresistant TNBC.
2024-05-17 | GSE264252 | GEO