prostate cancer Flashcards
Explain the involvement of the Androgen Receptor (AR) in AndrogenIndependent Prostate Cancer
The androgen receptor (AR) is a nuclear hormone receptor activated by binding to androgens like testosterone and dihydrotestosterone (DHT). It plays a key role in regulating genes involved in prostate cell growth and survival.
In typical prostate cancer, AR signaling is driven by androgens, which stimulate tumor growth. Early-stage prostate cancer often responds well to androgen deprivation therapy (ADT), which reduces androgen levels.
Over time, prostate cancer can evolve into an androgen-independent or castration-resistant form (CRPC). This shift occurs through several mechanisms:
AR Mutations: Mutations in AR can lead to ligand-independent activation, allowing the receptor to signal without androgens.
AR Amplification: Overexpression of AR can make prostate cancer cells hypersensitive to low levels of androgens or even other steroids.
Altered Signaling Pathways: Crosstalk with other growth factor receptors and signaling pathways (e.g., PI3K, MAPK) can bypass androgen dependence, maintaining AR activation.
Increased Local Androgen Synthesis: Some prostate cancer cells can produce androgens within the tumor microenvironment, activating AR even in low systemic androgen conditions.
Implications: Androgen-independent AR activity promotes continued tumor growth and progression despite androgen deprivation, complicating treatment and necessitating alternative therapies targeting AR or associated pathways.
Explain how the molecular drivers of Prostate Cancer may lead to
metastatic disease.
Genetic Alterations: Mutations in genes like TP53, KRAS, and PTEN can disrupt cell cycle regulation, promoting uncontrolled proliferation and survival, which may drive tumor progression and metastasis.
Androgen Receptor (AR) Dysregulation: Overexpression, mutations, or activation of AR in androgen-independent prostate cancer enables sustained growth and metastasis despite low androgen levels.
EMT (Epithelial-to-Mesenchymal Transition): Activation of signaling pathways (e.g., TGF-β, Wnt, Notch) triggers EMT, where prostate cancer cells lose epithelial characteristics, acquire motility, and invade surrounding tissues, promoting metastasis.
Angiogenesis: Dysregulated signaling, such as VEGF production, promotes the formation of new blood vessels, aiding tumor growth and providing routes for cancer cells to spread.
Bone Microenvironment: Prostate cancer frequently metastasizes to bones. Altered signaling in cancer cells enhances their ability to interact with bone stromal cells, leading to osteoblastic and osteoclastic activity that supports metastatic growth.
