PI3K and Cancer: Lessons, Challenges and Opportunities
By D. Fruman, C. Rommel. Nature reviews. Drug discovery, 2014
1,640 citations recorded by the source corpus.
The central role of phosphoinositide 3-kinase (PI3K) activation in tumour cell biology has prompted a sizeable effort to target PI3K and/or downstream kinases such as AKT and mammalian target of rapamycin (mTOR) in cancer. However, emerging clinical data show limited single-agent activity of inhibitors targeting PI3K, AKT or mTOR at tolerated doses. One exception is the response to PI3Kδ inhibitors in chronic lymphocytic leukaemia, where a combination of cell-intrinsic and -extrinsic activities drive efficacy. Here, we review key challenges and opportunities for the clinical development of inhibitors targeting the PI3K–AKT–mTOR pathway. Through a greater focus on patient selection, increased understanding of immune modulation and strategic application of rational combinations, it should be possible to realize the potential of this promising class of targeted anticancer agents.
Subfields: Genetics, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/428a443ba8ec9d1b5b3fd905463d5dfafef92a67
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Citations in the corpus
- Breast cancer development and progression: Risk factors, cancer stem cells, signaling pathways, genomics, and molecular pathogenesis (2018, background): “Conversely, human regulatory subunits p85a, p85b, and p55g are encoded by PI3K regulatory subunit 1 (PIK3R1), PIK3R2, and PIK3R3, respectively.(231) PI3K signaling is initiated by the growth factor activated receptor tyrosine kinase, or RAS protein, though direct interaction with p85 or via adaptor ”
- RAS isoforms and mutations in cancer at a glance (2016, background): “…plasma membrane (phosphodiesterase delta) (Zimmermann et al., 2013), (iii) inhibitors of downstream effector signaling (e.g. RAF or PI3K effectors) (Fruman and Rommel, 2014; Samatar and Poulikakos, 2014), (iv) inhibitors of processes that support the increased metabolic needs of cancer cells (e.g.…”