Biomarkers and Patient Selection for PI3K/Akt/mTOR Targeted Therapies: Current Status and Future Directions

Bartlett, John M.S.

doi:10.3816/cbc.2010.s.017

Cited by 28 publications

(10 citation statements)

References 69 publications

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“…Primary candidates include mutations in PIK3CA, PTEN, AKT, as well as overexpression of phosphorylated mTOR and phosphorylated AKT (pAKT). [23][24][25] Preliminary results from a group of patients with advanced solid tumors, including endometrial cancer, harboring PIK3CA mutations that were treated with PI3K/AKT/mTOR inhibitors alone or in combination with other agents, reveals higher than expected response rates (35%) in a highly pretreated group of patients. 26 Interestingly, the presence of KRAS mutations appeared to confer resistance in certain tumor types in the retrospective study by Janku and colleagues.…”

Section: Pathways Of Interest In Endometrial Cancermentioning

confidence: 99%

Personalized therapy in endometrial cancer: Challenges and opportunities

Westin

Broaddus

2012

Cancer Biology & Therapy

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Early stage endometrial cancer is generally curable. However, progress in the treatment of advanced and recurrent endometrial cancer has been limited. This has led to a shift from the use of traditional chemotherapeutic agents and radiotherapy regimens to the promising area of targeted therapy, given the large number of druggable molecular alterations found in endometrial cancer. To maximize the effects of directed targeted therapy, careful molecular characterization of the endometrial tumor is necessary. This represents an important difference in the use of targeted therapy vs. traditional chemotherapy or radiation treatment. This review will discuss relevant pathways to target in endometrial cancer as well as the challenges that arise during development of a personalized oncology approach.

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Section: Pathways Of Interest In Endometrial Cancermentioning

confidence: 99%

Personalized therapy in endometrial cancer: Challenges and opportunities

Westin

Broaddus

2012

Cancer Biology & Therapy

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“…Samples, where necessary, underwent sodium-acetate/ethanol re-precipitation. We selected 33 genes of interest from key functional nodes in the PIK3CA signaling pathway 60 and 6 reference genes (Supplementary Table 16 , Supplementary Methods section 4). Probes for each gene were designed and synthesized at NanoString Technologies (Washington, USA).…”

Section: Methodsmentioning

confidence: 99%

Pathway-based subnetworks enable cross-disease biomarker discovery

et al. 2018

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Biomarkers lie at the heart of precision medicine. Surprisingly, while rapid genomic profiling is becoming ubiquitous, the development of biomarkers usually involves the application of bespoke techniques that cannot be directly applied to other datasets. There is an urgent need for a systematic methodology to create biologically-interpretable molecular models that robustly predict key phenotypes. Here we present SIMMS (Subnetwork Integration for Multi-Modal Signatures): an algorithm that fragments pathways into functional modules and uses these to predict phenotypes. We apply SIMMS to multiple data types across five diseases, and in each it reproducibly identifies known and novel subtypes, and makes superior predictions to the best bespoke approaches. To demonstrate its ability on a new dataset, we profile 33 genes/nodes of the PI3K pathway in 1734 FFPE breast tumors and create a four-subnetwork prediction model. This model out-performs a clinically-validated molecular test in an independent cohort of 1742 patients. SIMMS is generic and enables systematic data integration for robust biomarker discovery.

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“…Many relevant molecular abnormalities in endometrial cancer are linked, either in a direct or indirect fashion to the PI3K/AKT/mTOR pathway [17][18][19] . Potential candidates might include PTEN, phospho-AKT, PIK3CA, phospho-mTOR, pS6rp.…”

Section: Discussionmentioning

confidence: 99%