Review: Mammalian Target of Rapamycin (mTOR) Pathway Is Critical in Developing Most Renal Cell Tumors

Ann Clin Lab Sci. 2023 Jan;53(1):3-13.


Objective: Various renal cell carcinomas (RCC) are derived from different segments of the renal tubular origin, which determines their morphological and immunohistochemical phenotype and their molecular signaling pathway as a therapeutic target. Most of these tumors utilize the mammalian target of rapamycin (mTOR) pathway to activate pathways involving metabolic and nutritional supplies.

Methods: Overexpressed mTOR signals are reported in more than 90% of the most common types of RCC. Many new renal tumor entities have been reported in recent years.

Results: Among them, somatic mutations in tuberous sclerosis complex (TSC) result in loss of its normal inhibitory control over mTOR, thus promoting mTOR-associated proliferative activities in several new renal neoplastic entities including RCC with fibromyomatous stroma (RCCFMS), eosinophilic vacuolated tumor, eosinophilic solid & cystic RCC, and low-grade oncocytic tumor.

Conclusions: This short review provides a comprehensive correlation of tumor morphology and immunohistochemical phenotype with renal tubular differentiation and their shared mTOR. These essential pieces of knowledge are vital in the diagnosis and clinical management of renal cell neoplasms.

Keywords: mTOR; mutations; renal cell neoplasm; treatment resistance; tuberous sclerosis complex.

MeSH terms

  • Carcinoma, Renal Cell* / genetics
  • Carcinoma, Renal Cell* / pathology
  • Humans
  • Kidney Neoplasms* / pathology
  • Mutation
  • TOR Serine-Threonine Kinases / metabolism
  • Tuberous Sclerosis Complex 2 Protein / genetics


  • Tuberous Sclerosis Complex 2 Protein
  • TOR Serine-Threonine Kinases
  • MTOR protein, human