scholarly journals The Current Status and Future Prospects of Oncolytic Viruses in Clinical Trials against Melanoma, Glioma, Pancreatic, and Breast Cancers

Cancers ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 356 ◽  
Author(s):  
Ibrahim Eissa ◽  
Itzel Bustos-Villalobos ◽  
Toru Ichinose ◽  
Shigeru Matsumura ◽  
Yoshinori Naoe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Checkpoint Inhibitors ◽  
Oncolytic Viruses ◽  
Current Status ◽  
European Medicines Agency ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Future Prospects ◽  
Phase I Clinical Trials

Oncolytic viral therapy has been accepted as a standard immunotherapy since talimogene laherparepvec (T-VEC, Imlygic®) was approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for melanoma treatment in 2015. Various oncolytic viruses (OVs), such as HF10 (Canerpaturev—C-REV) and CVA21 (CAVATAK), are now actively being developed in phase II as monotherapies, or in combination with immune checkpoint inhibitors against melanoma. Moreover, in glioma, several OVs have clearly demonstrated both safety and a promising efficacy in the phase I clinical trials. Additionally, the safety of several OVs, such as pelareorep (Reolysin®), proved their safety and efficacy in combination with paclitaxel in breast cancer patients, but the outcomes of OVs as monotherapy against breast cancer have not provided a clear therapeutic strategy for OVs. The clinical trials of OVs against pancreatic cancer have not yet demonstrated efficacy as either monotherapy or as part of combination therapy. However, there are several oncolytic viruses that have successfully proved their efficacy in different preclinical models. In this review, we mainly focused on the oncolytic viruses that transitioned into clinical trials against melanoma, glioma, pancreatic, and breast cancers. Hence, we described the current status and future prospects of OVs clinical trials against melanoma, glioma, pancreatic, and breast cancers.

scholarly journals The molecular landscape of Asian breast cancers reveals clinically relevant population-specific differences

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Jia-Wern Pan ◽  
Muhammad Mamduh Ahmad Zabidi ◽  
Pei-Sze Ng ◽  
Mei-Yee Meng ◽  
Siti Norhidayu Hasan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Somatic Mutations ◽  
Checkpoint Inhibitors ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Breast Tumours ◽  
Different Populations ◽  
Caucasian Women ◽  
Molecular Landscape ◽  
Immune Score

AbstractMolecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.

scholarly journals Checkpoint Inhibitors in Breast Cancer - Current Status and Future Directions

Breast Care ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Joachim Bischoff
Keyword(s):  
Breast Cancer ◽  
T Cell Activation ◽  
Cell Activation ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Death Receptor ◽  
Target Population ◽  
Current Status ◽  
Immune Checkpoints ◽  
Breast Cancer Patients

Antineoplastic agents directly targeting tumor cells have represented the major strategy of systemic anticancer therapy for many years. Nevertheless, overcoming resistance mechanisms remains a great challenge because treatment options are limited in many cases. From this point of view, immunotherapeutic approaches seem promising in a broad spectrum of solid tumors. These include in particular the currently available inhibitors directed against immune checkpoints leading to a significant T-cell activation. To date, the programmed death receptor 1 (PD-1) and its ligand are the most prominent targets in this context. However, the role of checkpoint inhibitors in the treatment of breast cancer is still being debated, and the main focus is on triple-negative breast cancer patients as a target population in many ongoing trials. Moreover, the potential superiority of combinations with other anticancer drugs such as cytotoxics and targeted agents will be discussed.

scholarly journals Clinical outcomes of breast cancer patients treated in phase I clinical trials at University of Colorado Cancer Center

2020 ◽  
Vol 9 (23) ◽  
pp. 8801-8808
Author(s):  
Jennifer A. Weiss ◽  
Andrew Nicklawsky ◽  
Jodi A. Kagihara ◽  
Dexiang Gao ◽  
Christine Fisher ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Cancer Center ◽  
Breast Cancer Patients ◽  
Phase I Clinical Trials ◽  
University Of Colorado

SOLTI-1503 PROMETEO TRIAL: combination of talimogene laherparepvec with atezolizumab in early breast cancer

2020 ◽  
Author(s):  
Tomas Pascual ◽  
Juan M Cejalvo ◽  
Mafalda Oliveira ◽  
Maria Vidal ◽  
Estela Vega ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Early Breast Cancer ◽  
Residual Disease ◽  
Checkpoint Inhibitors ◽  
Oncolytic Viruses ◽  
Breast Cancer Patients ◽  
Talimogene Laherparepvec ◽  
Residual Cancer ◽  
Clinical Trial Registration

New treatment strategies such as immune checkpoint inhibitors and oncolytic viruses are opening new possibilities in cancer therapy. Preliminary results in melanoma and other tumors showed that the combination of talimogene laherparepvec with an anti-PD-1/PD-L1 or anti-CTLA4 has greater efficacy than either therapy alone, without additional safety concerns beyond those expected for each agent. The presence of residual cancer after neoadjuvant chemotherapy in early breast cancer patients is an unmet medical need. SOLTI-1503 PROMETEO is a window of opportunity trial, which evaluates the combination of talimogene laherparepvec in combination with atezolizumab in women with operable HER2-negative breast cancer who present residual disease after neoadjuvant chemotherapy. The primary end point is the rate of residual cancer burden 0/1. Clinical Trial Registration: NCT03802604 (ClinicalTrials.gov).

Clinical and pathologic characteristics of patients with PI3K-mutant breast cancers.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 8-8
Author(s):  
M. Cooper Lloyd ◽  
Melinda Sanders ◽  
Maria Gabriela Kuba ◽  
Jaime Farley ◽  
Darson Lai ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Cancer Patients ◽  
Care Center ◽  
Tertiary Care ◽  
Pi3k Pathway ◽  
Recurrence Free Survival ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Free Survival

8 Background: Mutations in PIK3CA are the most common somatic alterations in breast cancer and represent a potentially useful therapeutic target. As more PI3K pathway inhibitors enter the clinical arena, it is important to understand the characteristics of patients harboring mutations. This study seeks to identify the clinico/pathological characteristics of PI3K mutant breast cancers in patients evaluated at Vanderbilt University Medical Center. Methods: Molecular profiling (SNaPShot) was used to detect mutations in three genes in the PI3K pathway (PIK3CA, PTEN, AKT1). Electronic medical records of breast cancer patients whose tumors underwent testing from June 2010 to January 2013 were reviewed. PI3K mutation rates, histological tumor grade, receptor status (ER/PR/HER2), and recurrence-free survival were tabulated. Results: Three hundred evaluable tests were identified, with PI3K mutations detected in 83/300 (28%). Patients with PI3K mutations were more likely to be ER/PR positive (73% vs. 48%; p<0.001) and less likely to be HER2 positive (6.0% vs. 20.7%, p=0.0022). Only 6/83 patients (7.2%) with triple negative cancers harbored PI3K mutations. 32% of patients with PI3K mutations participated in clinical trials, versus 25% without. Conclusions: Tumors with PI3K mutations were more likely to be ER/PR positive, of intermediate grade, and associated with longer recurrence-free survival. Patients with PI3K mutations were more likely to participate in clinical trials. These data and the potential eligibility of patients harboring mutations for clinical trials support the prognostic and clinical utility of SNaPShot testing for all breast cancer patients at a tertiary care center. [Table: see text]

scholarly journals Determining Factors in the Therapeutic Success of Checkpoint Immunotherapies against PD-L1 in Breast Cancer: A Focus on Epithelial-Mesenchymal Transition Activation

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Mariana Segovia-Mendoza ◽  
Susana Romero-Garcia ◽  
Cristina Lemini ◽  
Heriberto Prado-Garcia
Keyword(s):  
Breast Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Checkpoint Inhibitors ◽  
Death Receptor ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Therapeutic Success ◽  
Mesenchymal Transition ◽  
Determining Factors ◽  
Triple Negative Phenotype

Breast cancer is the most common neoplasm diagnosed in women around the world. Checkpoint inhibitors, targeting the programmed death receptor-1 or ligand-1 (PD-1/PD-L1) axis, have dramatically changed the outcome of cancer treatment. These therapies have been recently considered as alternatives for treatment of breast cancers, in particular those with the triple-negative phenotype (TNBC). A further understanding of the regulatory mechanisms of PD-L1 expression is required to increase the benefit of PD-L1/PD-1 checkpoint immunotherapy in breast cancer patients. In this review, we will compile the most recent studies evaluating PD-1/PD-L1 checkpoint inhibitors in breast cancer. We review factors that determine the therapeutic success of PD-1/PD-L1 immunotherapies in this pathology. In particular, we focus on pathways that interconnect the epithelial-mesenchymal transition (EMT) with regulation of PD-L1 expression. We also discuss the relationship between cellular metabolic pathways and PD-L1 expression that are involved in the promotion of resistance in TNBC.

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