Androgen receptor (AR) has a pivotal role in physiological pubertal development of mammary gland and its age-related modification as well as in breast cancer (BC) onset. The AR is the most prevalent sex steroid receptor in in situ, invasive and metastatic breast cancers, occurring in up to 90% of primary tumors and 75% of metastases. However, use of AR as a biomarker or druggable target in BC patients only recently has emerged and it is still controversial. The majority of data on the role of AR in breast cancer arises from studies conducted in triple-negative BC (TNBC). In this subset of BC, the expression of AR is lower than the other subtypes, ranging from 15 to 30%. To make more complex this scenario, re-introduction of AR drives the growth of AR-negative TNBC. Thus, further sub-classification based on the presence or not of AR has been proposed for this breast cancer subset. These cancers have been named luminal androgen receptor (LAR) subtype and quadruple negative breast cancer (QNBC), respectively. Currently there are several open clinical trials in TNBC patients to verify the effectiveness of anti-androgen therapy.
Despite the progress made in the knowledge of BC pathogenesis, the biological mechanism underlying the role of AR in this disease is yet not fully understood. AR target a plethora of genes, but knowledge of their roles in different BC subtypes is scant. Moreover, the effect mediated by AR on tumor growth, as already seen in prostate cancer, seems to be not only dependent on its transcriptional activity, but also by its non-genomic/non-transcriptional mode of action, which occurs through Src-dependent pathway and impinges on cell proliferation. Furthermore, much evidence has shown an important role of non-genomic pathways activated by AR/filamin A complex in tumor cell motility and invasiveness.
This Research Topic focuses on studies (including e.g. original research, perspectives, mini-reviews, commentaries and opinion papers) that investigate and discuss:
1) the role of androgen receptor in specific breast cancer subtypes;
2) the genetic signature associated with activation of AR acting as transcriptional factor in breast cancer;
3) the importance of non genomic/non-transcriptional action mediated by AR in breast cancer;
4) the role of AR in BC spreading and metastasis, including the putative role of the receptor in tumor microenvironment;
5) the findings obtained from clinical trials investigating the effectiveness of anti-androgen therapies in breast cancer.
Androgen receptor (AR) has a pivotal role in physiological pubertal development of mammary gland and its age-related modification as well as in breast cancer (BC) onset. The AR is the most prevalent sex steroid receptor in in situ, invasive and metastatic breast cancers, occurring in up to 90% of primary tumors and 75% of metastases. However, use of AR as a biomarker or druggable target in BC patients only recently has emerged and it is still controversial. The majority of data on the role of AR in breast cancer arises from studies conducted in triple-negative BC (TNBC). In this subset of BC, the expression of AR is lower than the other subtypes, ranging from 15 to 30%. To make more complex this scenario, re-introduction of AR drives the growth of AR-negative TNBC. Thus, further sub-classification based on the presence or not of AR has been proposed for this breast cancer subset. These cancers have been named luminal androgen receptor (LAR) subtype and quadruple negative breast cancer (QNBC), respectively. Currently there are several open clinical trials in TNBC patients to verify the effectiveness of anti-androgen therapy.
Despite the progress made in the knowledge of BC pathogenesis, the biological mechanism underlying the role of AR in this disease is yet not fully understood. AR target a plethora of genes, but knowledge of their roles in different BC subtypes is scant. Moreover, the effect mediated by AR on tumor growth, as already seen in prostate cancer, seems to be not only dependent on its transcriptional activity, but also by its non-genomic/non-transcriptional mode of action, which occurs through Src-dependent pathway and impinges on cell proliferation. Furthermore, much evidence has shown an important role of non-genomic pathways activated by AR/filamin A complex in tumor cell motility and invasiveness.
This Research Topic focuses on studies (including e.g. original research, perspectives, mini-reviews, commentaries and opinion papers) that investigate and discuss:
1) the role of androgen receptor in specific breast cancer subtypes;
2) the genetic signature associated with activation of AR acting as transcriptional factor in breast cancer;
3) the importance of non genomic/non-transcriptional action mediated by AR in breast cancer;
4) the role of AR in BC spreading and metastasis, including the putative role of the receptor in tumor microenvironment;
5) the findings obtained from clinical trials investigating the effectiveness of anti-androgen therapies in breast cancer.
