Strategies targeting protein tyrosine phosphatase SHP2 for cancer therapy
Y Song, S Wang, M Zhao, X Yang… - Journal of medicinal …, 2022 - ACS Publications
The protein tyrosine phosphatase SHP2 encoded by PTPN11 is a promising therapeutic
target for cancer therapy, while the multifaceted roles of SHP2 complicate the drug discovery …
target for cancer therapy, while the multifaceted roles of SHP2 complicate the drug discovery …
[HTML][HTML] Targeting the undruggable oncogenic KRAS: the dawn of hope
KRAS mutations are the drivers of various cancers, including non–small cell lung cancer,
colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been …
colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been …
SHP2 inhibition diminishes KRASG12C cycling and promotes tumor microenvironment remodeling
KRAS is the most frequently mutated human oncogene, and KRAS inhibition has been a
longtime goal. Recently, inhibitors were developed that bind KRASG12C-GDP and react …
longtime goal. Recently, inhibitors were developed that bind KRASG12C-GDP and react …
Identification of TNO155, an allosteric SHP2 inhibitor for the treatment of cancer
MJ LaMarche, M Acker, A Argintaru… - Journal of medicinal …, 2020 - ACS Publications
SHP2 is a nonreceptor protein tyrosine phosphatase encoded by the PTPN11 gene and is
involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays …
involved in cell growth and differentiation via the MAPK signaling pathway. SHP2 also plays …
Combinations with allosteric SHP2 inhibitor TNO155 to block receptor tyrosine kinase signaling
C Liu, H Lu, H Wang, A Loo, X Zhang, G Yang… - Clinical Cancer …, 2021 - AACR
Purpose: SHP2 inhibitors offer an appealing and novel approach to inhibit receptor tyrosine
kinase (RTK) signaling, which is the oncogenic driver in many tumors or is frequently …
kinase (RTK) signaling, which is the oncogenic driver in many tumors or is frequently …
Identification of GDC-1971 (RLY-1971), a SHP2 inhibitor designed for the treatment of solid tumors
AM Taylor, BR Williams, F Giordanetto… - Journal of Medicinal …, 2023 - ACS Publications
Protein tyrosine phosphatase SHP2 mediates RAS-driven MAPK signaling and has
emerged in recent years as a target of interest in oncology, both for treating with a single …
emerged in recent years as a target of interest in oncology, both for treating with a single …
Genome-wide CRISPR/Cas9 screens reveal shared and cell-specific mechanisms of resistance to SHP2 inhibition
SHP2 (PTPN11) acts upstream of SOS1/2 to enable RAS activation. Allosteric SHP2
inhibitors (SHP2i) in the clinic prevent SHP2 activation, block proliferation of RTK-or cycling …
inhibitors (SHP2i) in the clinic prevent SHP2 activation, block proliferation of RTK-or cycling …
Extensive preclinical validation of combined RMC-4550 and LY3214996 supports clinical investigation for KRAS mutant pancreatic cancer
KJ Frank, A Mulero-Sanchez, A Berninger… - Cell Reports …, 2022 - cell.com
Over 90% of pancreatic cancers present mutations in KRAS, one of the most common
oncogenic drivers overall. Currently, most KRAS mutant isoforms cannot be targeted directly …
oncogenic drivers overall. Currently, most KRAS mutant isoforms cannot be targeted directly …
Allosteric inhibition of SHP2 stimulates antitumor immunity by transforming the immunosuppressive environment
E Quintana, CJ Schulze, DR Myers, TJ Choy, K Mordec… - Cancer research, 2020 - AACR
The protein tyrosine phosphatase SHP2 binds to phosphorylated signaling motifs on
regulatory immunoreceptors including PD-1, but its functional role in tumor immunity is …
regulatory immunoreceptors including PD-1, but its functional role in tumor immunity is …
Druggable cancer phosphatases
The phosphorylation status of oncoproteins is regulated by both kinases and phosphatases.
Kinase inhibitors are rarely sufficient for successful cancer treatment, and phosphatases …
Kinase inhibitors are rarely sufficient for successful cancer treatment, and phosphatases …