Macropinocytosis: the Achilles’ heel of pancreatic cancer?

Andreasson, Carl; Ansari, Daniel; Ekbom, Fredrik; Andersson, Roland

doi:10.1080/00365521.2020.1855471

Cited by 2 publications

(1 citation statement)

References 28 publications

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“…Other metabolic pathways, namely macropinocytosis, an endocytic mechanism that PDAC cells utilize to accumulate essential amino acids ( Commisso et al, 2013 ; Andreasson et al, 2020 ) and cholesterol metabolism ( Chen et al, 2015 ; Guillaumond et al, 2015 ) also play significant roles in PDAC progression. Epidemiological and other studies have shown that statins, i.e., drugs reducing serum concentration of cholesterol, can be used to reduce the tumor load and improve the survival of PDAC patients ( Walker et al, 2015 ; Wu et al, 2015 ; Huang et al, 2016 ).…”

Section: Metabolic Alterations Drive Pdac Progressionmentioning

confidence: 99%

Context Matters—Why We Need to Change From a One Size Fits all Approach to Made-to-Measure Therapies for Individual Patients With Pancreatic Cancer

Sankarasubramanian¹,

Pfohl

Regenbrecht³

et al. 2021

Front. Cell Dev. Biol.

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Pancreatic cancer is one of the deadliest cancers and remains a major unsolved health problem. While pancreatic ductal adenocarcinoma (PDAC) is associated with driver mutations in only four major genes (KRAS, TP53, SMAD4, and CDKN2A), every tumor differs in its molecular landscape, histology, and prognosis. It is crucial to understand and consider these differences to be able to tailor treatment regimens specific to the vulnerabilities of the individual tumor to enhance patient outcome. This review focuses on the heterogeneity of pancreatic tumor cells and how in addition to genetic alterations, the subsequent dysregulation of multiple signaling cascades at various levels, epigenetic and metabolic factors contribute to the oncogenesis of PDAC and compensate for each other in driving cancer progression if one is tackled by a therapeutic approach. This implicates that besides the need for new combinatorial therapies for PDAC, a personalized approach for treating this highly complex cancer is required. A strategy that combines both a target-based and phenotypic approach to identify an effective treatment, like Reverse Clinical Engineering® using patient-derived organoids, is discussed as a promising way forward in the field of personalized medicine to tackle this deadly disease.

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