Targeting adenosine receptor 2B in triple negative breast cancer

Abstract

In the review "Role of adenosine in tumor progression: focus on A2B receptor as potential therapeutic target", Sorrentino and Morello make a compelling case for considering adenosine 2B receptor (A2BR) as a target in cancer therapy (J Cancer Metastasis Treat 2017;3:127-38). A large body of evidence has accumulated suggesting A2BR to play an active role in tumor immune suppression and metastasis. Thus, this commentary will discuss the intriguing possibility of targeting A2BR in specific breast cancers that express high levels of A2BR and attract infiltrating immune cells. TRIPLE NEGATIVE BREAST CANCER IS SUSCEPTIVE TO IMMUNE MODULATIONTriple negative breast cancer (TNBC) is an aggressive subtype of breast cancer that disproportionally affects younger women and those of African origins, compared with Caucasians [1,2] . TNBC is devoid of the three receptors that classify and define most mammary cancers: estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) [3] . The lack of these receptors reduces the efficacy of targeted therapies for this cancer type, limiting treatment options to chemotherapeutic agents, ionizing radiation and surgery. TNBC patients are therefore in dire need for novel targeted therapies.Breast cancer has long been thought of as a non-immunogenic malignancy. However, a growing body of evidence suggests that this is not the case for all breast cancers. Tumor-infiltrating lymphocytes (TILs) are the most widely studied immune cells and include T cells and B cells. TILs are part of a larger category of infiltrating immune cells that include natural killer (NK) cells, macrophages, neutrophils, dendritic cells,

Molecular pathways enhance drug response prediction using transfer learning from cell lines to tumors and patient-derived xenografts

“…Moreover, signals related to this pathway have been associated with drug resistance (or poor clinical outcomes) in breast cancer. For example, CD163-mediated anti-inflammatory response 22,23 , Adenosine receptor 2B (ADORA2B) mediated anti-inflammatory cytokines production 24 and IL10 synthesis that plays a role in immune escape 25 . Together, our finding supports the current knowledge that cellular activity in the mTOR signaling pathway might affect the drug sensitivity in tumors.…”

Endorsement of TNBC Biomarkers in Precision Therapy by Nanotechnology

“…Interestingly, it was also revealed that Ado stimulated the expression of VEGF, which leads to enhanced intratumoral blood flow and angiogenesis by mediating purinergic P1 receptors, i.e., A2BR. Likewise, apart from VEGF, the activation of A2BR within the microvasculature also regulates the expression of other angiogenic factors like IL-8 and bFGF as well as results in the proliferation of cells which have an impact on cancer growth, invasion, and migration by inducing neo-vascularization within surrounding areas of cancer [36,37].…”

A2B Adenosine Receptor and Cancer

“…Mittal et al [7] suggested that high A 2B AR expression is associated with worse prognoses in triple-negative breast cancer (TNBC). In a TNBC mouse model, A 2B AR activation increased metastasis [42], while A 2B AR antagonism in mouse models reduced the tumor burden by immune mechanisms and action on tumor cells. The high A 2B AR expression has also been found in many human tumor cell lines, such as PC3 prostate, T24 bladder, 1321N1 astrocytoma [35], U373MG astrocytoma [43], MDA-MB-231 breast [20], Jurkat T cells [44], BON-1 pancreatic and KRJ-I intestinal [45], A375 melanoma [46], and THP-1 human monocytes [47].…”