We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Efficacy of PARP and PI3K/Akt inhibition in advanced infiltrative breast cancers with germline BRCA mutations: a narrative review.
- Authors
Baskaran, Geethan
- Abstract
Triple negative breast cancer (TNBC) remains as an aggressive form of cancer and represents 10-15% of all diagnosed breast cancers. Despite the continued integration of personalized medicine into public healthcare through public precision health (PPH), TNBC has the poorest prognosis of all breast cancer subtypes, with a 5-year mortality rate of 40%. TNBC is characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and the lack of HER2 receptor overexpression. Thus, personalized therapies that target cell surface receptors are largely ineffective for TNBC patients. An alternative approach involves exploiting synthetic lethality to treat tumours without specifically targeting receptors. TNBC is associated with BRCA mutations, and targeting Poly ADP-ribose polymerase (PARP) in these cancers can trigger synthetic lethality. However, resistance to PARP inhibition is possible due to its connection to the PI3K/Akt pathway. The intertwined nature of both PARP and PI3K/Akt pathways calls for combinatory inhibitor-based treatment arms that can overcome acquired resistance. The need to treat patients who resist either PI3K/Akt or PARP inhibition necessitates research into possible therapeutic routes of dual inhibition. Analysis of past pre-clinical and clinical trials involving PARPi and/or PI3Ki TNBC therapy can provide insight into its efficacy and guide future developments.
- Subjects
BREAST tumor diagnosis; THERAPEUTIC use of antineoplastic agents; DRUG efficacy; GENETIC mutation; BRCA genes; PROTEIN kinase inhibitors; CELL receptors; DRUG resistance; ESTROGEN receptors; TRANSFERASES; BREAST tumors; ENZYME inhibitors; PROGESTERONE receptors; EVALUATION
- Publication
University of Toronto Medical Journal, 2022, Vol 99, Issue 3, p51
- ISSN
0833-2207
- Publication type
Article