Mechanism of Disease

In PTEN-deficient mAPMN/S prostate cancer, 2 different pathways drive tumor growth1-3

  • Typically, the AR pathway is the primary driver of tumor progression in prostate cancer
  • However, both the PI3K/AKT/PTEN and AR pathways function as complementary drivers of tumor progression in PTEN-deficient mAPMN/S prostate cancer
  • When only the AR pathway is targeted, the PI3K/AKT/PTEN pathway provides an alternative mechanism for oncogenic signaling and cell proliferation

The PI3K/AKT/PTEN pathway can independently drive tumor growth in PTEN-deficient mAPMN/S prostate cancer despite AR-targeted treatment3

Mechanism of Action

TRUQAP + abiraterone: The first and only combination that targets 2 critical pathways in PTEN-deficient mAPMN/S prostate cancer1,4

TRUQAP® (capivasertib) + abiraterone leverage the dual power of AKT inhibition + androgen biosynthesis inhibition to reduce signaling that drives tumor growth in these key pathways.3-6

As observed in preclinical models:

TRUQAP Mechanism of Action Within The PI3K/AKT/PTEN PathwayTRUQAP Mechanism of Action Within The PI3K/AKT/PTEN Pathway

Graphic illustrating the TRUQAP mechanism of action within the PI3K/AKT/PTEN pathway and the abiraterone mechanism of action within the AR pathway. Highlights how TRUQAP works in combination with abiraterone.3-7

Learn about PTEN deficiency and the importance of testing in mAPMN/S prostate cancer

See PTEN deficiency and testing

Explore the efficacy of TRUQAP

See TRUQAP efficacy data

AKT=serine/threonine protein kinase; AR=androgen receptor; CYP17=cytochrome P450 17α-hydroxylase/17,20-lyase; mAPMN/S=metastatic androgen pathway modulation-naïve/sensitive; mHSPC=metastatic hormone-sensitive prostate cancer; PI3K=phosphoinositide 3-kinase; PTEN=phosphatase and tensin homolog.

References: 1. Carver BS, Chapinski C, Wongvipat J, et al. Reciprocal feedback regulation of PI3K and androgen receptor signaling in PTEN-deficient prostate cancer. Cancer Cell. 2011;19(5):575-586. doi:10.1016/j.ccr.2011.04.008 2. Messner EA, Steele TM, Tsamouri MM, et al. The androgen receptor in prostate cancer: effect of structure, ligands and spliced variants on therapy. Biomedicines. 2020;8(10):422. doi:10.3390/biomedicines8100422 3. Marques RB, Aghai A, de Ridder CMA, et al. High efficacy of combination therapy using PI3K/AKT inhibitors with androgen deprivation in prostate cancer preclinical models. Eur Urol. 2015;67(6):1177-1185. doi:10.1016/j.eururo.2014.08.053 4. TRUQAP® (capivasertib) [prescribing information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 5. ZYTIGA® (abiraterone acetate) tablets [prescribing information]. Horsham, PA: Janssen Biotech, Inc.; 2024. 6. YONSA® (abiraterone acetate) tablets [prescribing information]. Cranbury, NJ: Sun Pharmaceutical Industries, Inc.; 2022. 7. Bolek H, Yazgan SC, Yekedüz E, et al. Androgen receptor pathway inhibitors and drug-drug interactions in prostate cancer. ESMO Open. 2024;9(11):103736. doi:10.1016/j.esmoop.2024.103736