A phase I/Ib study evaluating GDC-0077 (inavolisib) + palbociclib (palbo) + fulvestrant in patients (pts) with PIK3CA-mutant (mut), hormone receptor-positive/HER2-negative metastatic breast cancer (HR+/HER2- mBC)

Schmid, Peter; Bedard, PL; Jhaveri, Komal; Hamilton, Erika; Italiano, Antoîne; Kalinsky, Kevin; Krop, IE; Oliveira, Mafalda; Saura, Cristina; Turner, Nicholas C.; Varga, Andréa; Hutchinson, Katie; Lei, Guiyuan; Royer-Joo, Stephanie; Thomas, PS; Jl, Schutzman; Juric, Dejan

doi:10.1055/s-0041-1730220

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“…Inavolisib exhibits strong efficacy in breast cancer patients, and several clinical studies have already been performed in combination with other drugs. Inavolisib, in conjunction with palbociclib and fulvestrant, demonstrated preliminary antitumor activity and manageable safety in patients with PIK3CA-mutated breast cancer 82 . Several clinical trials are currently underway for the treatment of breast cancer patients.…”

Section: Pi3k Inhibitorsmentioning

confidence: 99%

Inhibitors of phosphoinositide 3-kinase (PI3K) and phosphoinositide 3-kinase-related protein kinase family (PIKK)

Huang,

You,

Nepovimova

et al. 2023

Journal of Enzyme Inhibition and Medicinal Chemistry

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Phosphoinositide 3-kinases (PI3K) and phosphoinositide 3-kinase-related protein kinases (PIKK) are two structurally related families of kinases that play vital roles in cell growth and DNA damage repair. Dysfunction of PIKK members and aberrant stimulation of the PI3K/AKT/mTOR signalling pathway are linked to a plethora of diseases including cancer. In recent decades, numerous inhibitors related to the PI3K/AKT/mTOR signalling have made great strides in cancer treatment, like copanlisib and sirolimus. Notably, most of the PIKK inhibitors (such as VX-970 and M3814) related to DNA damage response have also shown good efficacy in clinical trials. However, these drugs still require a suitable combination therapy to overcome drug resistance or improve antitumor activity. Based on the aforementioned facts, we summarised the efficacy of PIKK, PI3K, and AKT inhibitors in the therapy of human malignancies and the resistance mechanisms of targeted therapy, in order to provide deeper insights into cancer treatment.

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Section: Pi3k Inhibitorsmentioning

confidence: 99%