Breast Tumor Microenvironment: Emerging target of therapeutic phytochemicals

Malla, Rama Rao; Deepak, K.G.K.; Merchant, Neha; Dasari, Venkata Ramesh

doi:10.1016/j.phymed.2020.153227

Cited by 21 publications

(11 citation statements)

References 252 publications

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“…Triple negative breast cancer (TNBC) is one of the BC subtypes defined by the lack of ER, PR, and HER2 expression, making this BC phenotype the most pathologically aggressive, with a higher risk of local and distant relapses and being more challenging to control [ 4 , 5 , 6 ]. Recently, numerous studies have highlighted the immune checkpoints as a key player in TNBC modulation and prevention [ 7 , 8 ]. However, the limited availability of effective targeted therapies for this type of BC phenotype is attributed to the paucity of viable molecular targets and the sophisticated tumor microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Comparative Gene Signature of (−)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights

et al. 2021

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Triple negative breast cancer (TNBC) heterogeneity and limited therapeutic options confer its phenotypic aggressiveness. The discovery of anti-TNBC natural products with valid molecular target(s) and defined pharmacodynamic profile would facilitate their therapeutic nutraceutical use by TNBC patients. The extra-virgin olive oil (EVOO) is a key Mediterranean diet ingredient. S-(−)-Oleocanthal (OC) leads the bioactive anti-tumor EVOO phenolic ingredients. A previous study reported the solid dispersion formulated OC with (+)-xylitol (OC-X) suppressed the in vivo progression and recurrence of the TNBC MDA-MB-231 cells. This study investigates the ability of OC-X formulation to suppress the in vivo heterogeneous BC initiation and progression utilizing advanced preclinical transgenic MMTV-PyVT and TNBC PDX mouse models. Furthermore, the clustering of the gene expression profiles in MMTV-PyVT and PDX mouse tumors treated with OC-X acquired by a Clariom S microarray analysis identified the distinctly affected genes. Several affected novel signature genes identified in response to OC-X treatments and proved overlapped in both mouse and human tumor models, shedding some lights toward understanding the OC anticancer molecular mechanism and assisting in predicting prospective clinical outcomes. This study provides molecular and preclinical evidences of OC-X potential as a nutraceutical suppressing heterogeneous TNBC model and offers preliminary gene-level therapeutic mechanistic insights.

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Section: Introductionmentioning

confidence: 99%

Comparative Gene Signature of (−)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights

et al. 2021

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“…Cancer immunotherapy combats MDR cancers by targeting various mechanisms that are involved in drug resistance. Immune infiltration of tumors creates a highly inflammatory microenvironment, with oxygen-deprived conditions supported by infiltrating immune cells, cytokines, and numerous growth factors [ 122 , 123 ]. Therefore, the modulation of immune responses may be a promising strategy to combat cancer.…”

Section: Allyl Sulfur Compounds In Garlicmentioning

confidence: 99%

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

Malla¹,

Marni²,

Chakraborty³

et al. 2022

Journal of Pharmaceutical Analysis

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“…C/H treatment improved the tumor suppression effect of anti-PD-1 antibody effectiveness in an orthotopic breast cancer model 4T1 breast cancer cells are used to create the triple-negative breast cancer model and have a poor prognosis due to complex immunosuppressive mechanisms in the TME. 34 The clinical response rates to immune checkpoint inhibition such as anti-PD-1 treatment remain low. 2 Therefore, we attempted to explore whether C/H treatment increased the tumor suppression activity of anti-PD-1 antibody treatment (Figure S4A).…”

Section: Cxcl2 In Combination With Hvj-e Treatment Induced N1 Neutrophil Infiltration In a 4t1 Metastasis Lung Modelmentioning

confidence: 99%

CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy

Pan

Nishikawa

Chang

et al. 2021

Molecular Therapy - Oncolytics

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Breast cancer has a high risk of metastasis; however, no effective treatment has been established. We developed a novel immunotherapy for breast cancer to enhance cytotoxic T lymphocytes against cancer cells using N1-type neutrophils with anti-tumor properties. For this purpose, we combined CXCL2 (CXC chemokine ligand 2) plasmid DNA with inactivated Sendai virus (hemagglutinating virus of Japan)-envelope (HVJ-E). The combination of CXCL2 DNA and HVJ-E (C/H) suppressed the growth of murine breast cancers in orthotopic syngeneic models by enhancing cytotoxic T lymphocytes and inhibited lung metastasis of breast cancer from primary lesions. N1-type neutrophils (CD11b + Ly6G + FAS + ) increased in the tumor microenvironment with C/H treatment, and tumor suppression and cytotoxic T lymphocyte activation from C/H was blocked after administrating anti-neutrophil antibodies, which indicates the role of N1-type neutrophils in cancer immunotherapy. We also demonstrated that the anti-tumor activities of C/H treatment were enhanced by the administration of anti-PD-1 antibodies through neutrophil-mediated cytotoxic T lymphocyte activation. Thus, the triple combination of C/H and anti-PD-1 antibody C/H treatment may provide an improvement in cancer immunotherapy.

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Breast Tumor Microenvironment: Emerging target of therapeutic phytochemicals

Cited by 21 publications

References 252 publications

Comparative Gene Signature of (−)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights

Comparative Gene Signature of (−)-Oleocanthal Formulation Treatments in Heterogeneous Triple Negative Breast Tumor Models: Oncological Therapeutic Target Insights

Diallyl disulfide and diallyl trisulfide in garlic as novel therapeutic agents to overcome drug resistance in breast cancer

CXCL2 combined with HVJ-E suppresses tumor growth and lung metastasis in breast cancer and enhances anti-PD-1 antibody therapy

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