The impact of androgen receptor (AR) activity in breast cancer (BCa) biology is unclear. We characterized and tested a novel therapy to an AR-governed target in BCa.
We evaluated the expression of prototypical AR-gene products human kallikrein 2 (hK2) and Prostate Specific Antigen (PSA) in BCa models. We screened 13 well-characterized BCa cell lines for hK2 and PSA production upon in-vitro hormone stimulation by testosterone (DHT). AR-positive lines were further evaluated by exposure to estrogen (17β-Estradiol) and the synthetic progestin D-Norgestrel. We then evaluated an anti-hK2 targeted radiotherapy platform (hu11B6), labeled with alpha (a)-particle emitting Actinium-225, to specifically treat AR-expressing BCa xenografts under hormone stimulation.
D-Norgestrel and DHT activated the AR-pathway, while 17β-Estradiol did not. Competitive binding for AR protein showed similar affinity between DHT and D-Norgestrel; indicating direct AR-ligand interaction. In vivo production of hK2 was sufficient to achieve site-specific delivery of therapeutic radionuclide to tumor tissue at >20-fold over background muscle uptake; effecting long-term local tumor control.
[225Ac]hu11B6 targeted radiotherapy was potentiated by DHT and by D-Norgestrel in murine xenograft models of BCa. AR activity in BCa correlates with kallikrein related peptidase-2 and can be activated by D-Norgestrel, a common contraceptive, and AR-induction can be harnessed for hK2-targeted BCa a-emitter radiotherapy.
Pharmacology, Toxicology and Pharmaceutical Science
3
6%
Agricultural and Biological Sciences
2
4%
Engineering
2
4%
Other
5
10%
Unknown
30
58%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 28 February 2020.
All research outputs
#21,255,570
of 34,350,842 outputs
Outputs from Clinical Cancer Research
#14,400
of 17,842 outputs
Outputs of similar age
#285,157
of 507,420 outputs
Outputs of similar age from Clinical Cancer Research
#184
of 264 outputs
Altmetric has tracked 34,350,842 research outputs across all sources so far. This one is in the 37th percentile – i.e., 37% of other outputs scored the same or lower than it.
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