Home / Science / Scientific References / Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer

2021 Oct;20(10):1820-1835. doi: 10.1158/1535-7163.MCT-21-0013.Epub 2021 Jul 12.

Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer

PMID: 34253596 PMCID: PMC8722383 DOI: 10.1158/1535-7163.MCT-21-0013

Erratum in

Correction: Protein Phosphatase 2A as a Therapeutic Target in Small Cell Lung Cancer.

Mirzapoiazova T, Xiao G, Mambetsariev B, Nasser MW, Miaou E, Singhal SS, Srivastava S, Mambetsariev I, Nelson MS, Nam A, Behal A, Arvanitis LD, Atri P, Muschen M, Tissot FLH, Miser J, Kovach JS, Sattler M, Batra SK, Kulkarni P, Salgia R.Mol Cancer Ther. 2022 Apr 1;21(4):700. doi: 10.1158/1535-7163.MCT-22-0104.PMID: 35373301 No abstract available.


Protein phosphatase 2A (PP2A), a serine/threonine phosphatase involved in the regulation of apoptosis, proliferation, and DNA-damage response, is overexpressed in many cancers, including small cell lung cancer (SCLC). Here we report that LB100, a small molecule inhibitor of PP2A, when combined with platinum-based chemotherapy, synergistically elicited an antitumor response both in vitro and in vivo with no apparent toxicity. Using inductively coupled plasma mass spectrometry, we determined quantitatively that sensitization via LB100 was mediated by increased uptake of carboplatin in SCLC cells. Treatment with LB100 alone or in combination resulted in inhibition of cell viability in two-dimensional culture and three-dimensional spheroid models of SCLC, reduced glucose uptake, and attenuated mitochondrial and glycolytic ATP production. Combining LB100 with atezolizumab increased the capacity of T cells to infiltrate and kill tumor spheroids, and combining LB100 with carboplatin caused hyperphosphorylation of the DNA repair marker γH2AX and enhanced apoptosis while attenuating MET signaling and invasion through an endothelial cell monolayer. Taken together, these data highlight the translational potential of inhibiting PP2A with LB100 in combination with platinum-based chemotherapy and immunotherapy in SCLC.