Targeting KRAS in pancreatic adenocarcinoma: Progress in demystifying the holy grail

doi:10.5306/wjco.v14.i8.285

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World J Clin Oncol. Aug 24, 2023; 14(8): 285-296
Published online Aug 24, 2023. doi: 10.5306/wjco.v14.i8.285

Table 2 Phosphoinositide 3-kinase-protein kinase-mammalian target of rapamycin-pathway inhibitors

Agent	Combination	Phase	NCT number¹
PI3K inhibitors (p110α) isoform
Alpelisib (BYL719)	Gemcitabine and abraxane	I	NCT02155088
Buparlisib (BKM120)	mFOLFOX6; trametinib (MEKi)	I; I	NCT01571024; NCT01155453
Pan-PI3K inhibitors
Copanlisib(BAY 80–6946)	N/A	I	NCT00962611
PI3K and mTOR inhibitors
Voxtalisib (SAR245409, XL765)	N/A	I	NCT00485719
Dactolisib(NVP-BEZ235)	MEK162 (MEKi)	I	NCT01337765
Gedatolisib (PF-05212384, PKI-587)	Palbociclib (CDKi)	I	NCT03065062
Pan-Akt inhibitors
MK2206	Monotherapy; dinaciclib (CDKi); selumitinib (MEKi) vs mFOLFOX6	I; I; II	NCT00848718; NCT01783171; NCT01658943
Afuresertib (GSK2110183)	Trametinib (MEKi); N/A	I; II	NCT01476137; NCT01531894
Uprosertib (GSK2141795)	Trametinib (MEKi)	I	NCT01138085
Oleandrin (PBI-05204)	N/A	II	NCT02329717
Perifosine	N/A	II; II	NCT00053924; NCT00059982
RX-0201	Gemcitabine	II	NCT01028495
Rapalogs (mTORC1 inhibitors)
Sirolimus (rapamycin)	Sunitinib (RTKi); N/A; metformin; vismodegib (SMOi)	I; II; I/II; I	NCT00583063; NCT00499486; NCT02048384; NCT01537107
Temsirolimus (CCI-779, Torisel)	Lenalidomide; gemcitabine; nivolumab (PD-1i)	I; I; I/II	NCT01183663; NCT00593008; NCT02423954
Everolimus (RAD001)	Sorafenib (RTKi); trametinib (MEKi); gemcitabine; cetuximab (EGFRi) and capecitabine; N/A	I; I; I/II; I/II; II	NCT00981162; NCT00955773; NCT00560963; NCT01077986; NCT00409292
Ridafirolimus	Bevacizumab (VEGFRi)	I	NCT00781846
mTORC1/2 inhibitors
Vistusertib (AZD2014)	N/A; selumitinib (MEKi); olaparib (PARPi)	I; II; II	NCT01026402; NCT02583542; NCT02576444

¹clinicaltrials.gov

PI3K: Phosphoinositide 3-kinase; NCT: National clinical trial; MEKi: Mitogen-activated protein kinase/ extracellular regulated protein kinases inhibitor; CDKi: Cyclin-dependent kinase inhibitor; RTKi: Receptor tyrosine kinase inhibitor; SMOi: Smoothened inhibitor; PD-1i: Programmed cell death receptor-1 inhibitor; EGFRi: Epidermal growth factor receptor inhibitor; VEGFRi: Vascular endothelial growth factor receptor inhibitor; mTOR: mammalian target of rapamycin; PARPi: Poly (ADP-ribose) polymerase inhibitor; N/A: Not applicable.

Citation: Elhariri A, Alhaj A, Ahn D, Sonbol MB, Bekaii-Saab T, Wu C, Rutenberg MS, Stauffer J, Starr J, Majeed U, Jones J, Borad M, Babiker H. Targeting KRAS in pancreatic adenocarcinoma: Progress in demystifying the holy grail. World J Clin Oncol 2023; 14(8): 285-296
URL: https://www.wjgnet.com/2218-4333/full/v14/i8/285.htm
DOI: https://dx.doi.org/10.5306/wjco.v14.i8.285