Androgen receptor: Structure, signaling, function and potential drug discovery biomarker in different breast cancer subtypes.

The Androgen Receptor (AR) is emerging as an important factor in the pathogenesis of breast cancer (BC), which is the most common malignancy worldwide. >70 % of AR expression in primary and metastatic breast tumors has been observed which suggests that AR may be a new marker and a potential therapeutic target among AR-positive BC patients. Biological insight into AR-positive breast cancer reveals that AR may cross-talk with several vital signaling pathways, including key molecules and receptors. Downstream signaling of AR might also affect many clinically important pathways that are emerging as clinical targets in BC. AR exhibits different behaviors depending on the breast cancer molecular subtype. Preliminary clinical research using AR-targeted drugs, which have already been FDA-approved for prostate cancer (PC), has given promising results for AR-positive breast cancer patients. However, since AR positivity's prognostic and predictive value remains uncertain, it is difficult to identify and stratify patients who would benefit from AR-targeted therapies alone. Thus, the need of the hour is to target the androgen receptor as a monotherapy or in combination with other conventional therapies which has proven to be an effective clinical strategy for the treatment of prostate cancer patients, and these therapeutic strategies are increasingly being investigated in breast cancer. Therefore, in this manuscript, we review the role of AR in various cellular processes that promote tumorigenesis and aggressiveness, in different subtypes of breast cancer, as well as discuss ongoing efforts to target AR for the more effective treatment and prevention of breast cancer.

Antitumor effects of polyphenol-rich extract of Euphoria longana seed by vascular endothelial growth factor and transforming growth factor-beta signaling inhibition in experimentally induced oral cancer in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Oral cancers are found to have high risk in South Central Asia due to exposure of various risk factors. Euphoria longana Lam. (EL) has been traditionally used to relieve insomnia, prevent amnesia, and treat palpitation. In addition, EL has been reported to have anti-inflammatory, anti-cancer, and antioxidant activities. The investigation was aimed to evaluate the mechanism of action and antitumor activity of polyphenol-rich EL seeds extract against oral cancer induced by 4-Nitroquinoline-1-oxide (4-NQO). MATERIALS AND METHODS: Seven groups of Sprague-Dawley rats were formulated: normal animals, oral cancer induced with 4-NQO, EL-treated normal control, EL-treated disease control from 0-day, EL-treated disease control from 60 days, 5-fluorouracil (5-FU)-treated disease control from day 60, and combined EL- and 5-FU-treated disease control animals from day 60. The animal tongue was smeared with 0.5% 4-NQO at frequency of thrice a week for 12 weeks to induce oral cancer. At the end of treatment, excised tongues were used for biochemical and tumour-specific parameters along with histopathology assessment. RESULTS: Treatment with EL, 5-FU, and combination of both in diseased animals exhibited significant improvement in interleukin-6, vascular endothelial growth factor (VEGF), and Transforming growth factor beta (TGF-ß) levels, antioxidant status together with histoarchitecture of the tongue tissue. In addition, the combination of both was slightly more effective than EL and 5-FU alone. CONCLUSION: Our data suggest antitumor activity of Euphoria longana Lam. Extract against 4-NQO induced oral cancer in rats, which could be attributed to alteration in the VEGF and TGF-ß signaling axis.