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Capivasertib as a Therapeutic Agent for Breast Cancer: Targeting AKT to Overcome Endocrine Resistance

Christos Damaskos1,2, Nikolaos Garmpis2,3, Nikolaos Arkadopoulos4

  • 1Department of Emergency Surgery, Laiko General Hospital, 11527 Athens, Greece.

Journal of Clinical Medicine
|May 27, 2026
PubMed

Insights

Capivasertib combined with fulvestrant improves progression-free survival in advanced HR+/HER2- breast cancer with PI3K/AKT pathway alterations. Further research is needed to optimize patient selection and overcome resistance mechanisms.

Area of Science:

  • Oncology
  • Pharmacology
  • Molecular Biology

Background:

  • Capivasertib is an AKT inhibitor for HR+/HER2- breast cancer with PI3K/AKT pathway alterations.
  • The PI3K/AKT/mTOR pathway is crucial in endocrine resistance and tumor progression in this breast cancer subtype.

Purpose of the Study:

  • To review clinical data on capivasertib efficacy as monotherapy or in combination.
  • To discuss biomarkers and resistance mechanisms related to capivasertib treatment.

Main Methods:

  • Literature search of PubMed for clinical trials on capivasertib in breast cancer.
  • Inclusion of studies on capivasertib monotherapy or in combination with fulvestrant, paclitaxel, or olaparib.

Main Results:

  • Capivasertib plus fulvestrant significantly prolongs progression-free survival in HR+/HER2- advanced breast cancer, especially with PIK3CA, AKT1, or PTEN alterations.
  • Combinations with paclitaxel or olaparib show additive/synergistic effects in triple-negative and DNA repair-deficient cancers.
  • Monotherapy offers modest benefit, primarily in AKT1-mutant tumors, with effective pathway inhibition.

Conclusions:

  • Capivasertib is a validated therapeutic for AKT signaling inhibition in breast cancer.
  • Combination with endocrine therapy shows the most promise.
  • Optimizing patient selection and combination strategies is essential to address resistance due to mTORC1 activation and signaling redundancy.
Keywords:
AKT inhibitorsbreast cancerbreast tumorscapivasertibendocrine resistance

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