RHEB-CSF1R signaling, autophagy, and metastatic plasticity in pancreatic cancer: Current advances, controversies, and translational opportunities

Table 2 Representative small molecules that modulate autophagy-and epithelial-mesenchymal transition-related pathways in pancreatic ductal adenocarcinoma

Agent/target	Signaling pathway	Effect on autophagy	Principal phenotypic effect	Ref.
Umbelliprenin	AKT/mTOR, Notch1	Induces autophagy	Inhibits cancer stemness and induces apoptosis	[42]
Alisertib	PI3K/AKT/mTOR, p38 MAPK, ERK1/2, Sirtuin 1	Induces autophagy	Suppresses EMT and induces cell-cycle arrest	[55]
Qingyihuaji formula	MAPK/ERK, PI3K/AKT/mTOR	Induces autophagy	Induces apoptosis	[44]
Tetrandrine	ROS-related signaling	Inhibits autophagy	Promotes ROS accumulation and enhances therapeutic efficacy	[46]
Rhus coriaria	Not specified	Induces autophagy	Induces apoptosis	[47]
Hernandezine	ROS/AMPK	Induces autophagic cell death	Promotes cancer-cell death	[48]
G6PD	AMPK-mTOR axis	Modulates autophagy	Promotes ferroptosis resistance	[43]
PITPNC1	KRAS-MYC axis	Inhibits autophagy	Links KRAS to MYC and restrains autophagy	[45]

AKT: Protein kinase B; PI3K: Phosphatidylinositol 3-kinase; mTOR: Mammalian target of rapamycin; EMT: Epithelial-mesenchymal transition; MAPK: Mitogen-activated protein kinase; Notch1: Notch homolog 1 (translocation-associated); ERK: Extracellular signal-regulated kinase; ROS: Reactive oxygen species; AMPK: Adenosine monophosphate-activated protein kinase; KRAS: Kirsten rat sarcoma viral oncogene homolog; MYC: Myelocytomatosis viral oncogene homolog.