Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

Randall, Jamie; Hunt, Allison L.; Nutcharoen, Aratara; Johnston, Laura; Chouraichi, Safae; Wang, Hongkun; Winer, Arthur; Wadlow, Raymond; Huynh, Jasmine; Davis, Justin; Corgiat, Brian; Bateman, Nicholas W.; Deeken, John F.; Petricoin, Emanuel F.; Conrads, Thomas P.; Cannon, Timothy L.

doi:10.1186/s12014-024-09476-7

Cited by 3 publications

References 44 publications

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Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort

Prasad,

Baldelli,

Blais

et al. 2024

Br J Cancer

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Background Mutations of the PIK3CA/AKT/mTOR axis are common events in metastatic breast cancers (MBCs). This study was designed to evaluate the extent to which genetic alterations of the PIK3CA/AKT/mTOR can predict protein activation of this signalling axis in MBCs. Methods Molecular profiles were generated by CLIA-certified laboratories from a real-world evidence cohort of 171 MBC patients. Genetic alterations of the PIK3CA pathway were measured using next-generation sequencing. Activation levels of AKT and downstream signalling molecules were quantified using two orthogonal proteomic methods. Protein activity was correlated with underlying genomic profiles and response to CDK4/6 inhibition in combination with endocrine treatment (ET). Results Oncogenic alterations of the PIK3CA/AKT/PTEN pathway were identified in 49.7% of cases. Genomic profiles emerged as poor predictors of protein activity (AUC:0.69), and AKT phosphorylation levels mimicked those of mutant lesions in 76.9% of wild-type tumours. High phosphorylation levels of the PI3K/AKT/mTOR downstream target p70S6 Kinase (T389) were associated with shorter PFS in patients treated with CDK4/6 inhibitors in combination with ET (HR:4.18 95%CI:1.19–14.63); this association was not seen when patients were classified by mutational status. Conclusions Phosphoprotein-based measurements of drug targets and downstream substrates should be captured along with genomic information to identify MBCs driven by the PI3K/AKT/mTOR signalling.

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Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort

Prasad,

Baldelli,

Blais

et al. 2024

Br J Cancer

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Integrating Functional Protein Drug Target Data into a Precision Oncology Molecular Tumor Board

Hunt,

Randall,

Mansukhani

et al. 2024

Preprint

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Collaborative review of molecular profiling data by multidisciplinary molecular tumor boards (MTB) is increasingly important for improving patient management and outcomes, though currently relies nearly exclusively on nucleic acid next-generation sequencing (NGS) and limited panels of immunohistochemistry-based protein abundance data. We examined the feasibility of incorporating real-time laser microdissection (LMD) enrichment of tumor epithelium and commercial CLIA-based reverse phase protein array (RPPA) protein drug target expression/activation profiling into our cancer center MTB to complement standard clinical NGS-based profiling. The LMD-RPPA workflow was performed within a therapeutically permissive timeframe with a median dwell time of nine days, during which specimens were processed outside of standard clinical workflows. The RPPA-generated data supported additional and/or alternative therapeutic considerations for 54% of profiled patients following review by the MTB. These findings suggest that integrating proteomic/phosphoproteomic and NGS-based genomic data creates opportunities to further personalize clinical decision-making for precision oncology.

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Current and future immunotherapeutic approaches in pancreatic cancer treatment

Farhangnia,

Khorramdelazad,

Nickho

et al. 2024

J Hematol Oncol

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Pancreatic cancer is a major cause of cancer-related death, but despondently, the outlook and prognosis for this resistant type of tumor have remained grim for a long time. Currently, it is extremely challenging to prevent or detect it early enough for effective treatment because patients rarely exhibit symptoms and there are no reliable indicators for detection. Most patients have advanced or spreading cancer that is difficult to treat, and treatments like chemotherapy and radiotherapy can only slightly prolong their life by a few months. Immunotherapy has revolutionized the treatment of pancreatic cancer, yet its effectiveness is limited by the tumor's immunosuppressive and hard-to-reach microenvironment. First, this article explains the immunosuppressive microenvironment of pancreatic cancer and highlights a wide range of immunotherapy options, including therapies involving oncolytic viruses, modified T cells (T-cell receptor [TCR]-engineered and chimeric antigen receptor [CAR] T-cell therapy), CAR natural killer cell therapy, cytokine-induced killer cells, immune checkpoint inhibitors, immunomodulators, cancer vaccines, and strategies targeting myeloid cells in the context of contemporary knowledge and future trends. Lastly, it discusses the main challenges ahead of pancreatic cancer immunotherapy.

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Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

Cited by 3 publications

References 44 publications

Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort

Functional activation of the AKT-mTOR signalling axis in a real-world metastatic breast cancer cohort

Integrating Functional Protein Drug Target Data into a Precision Oncology Molecular Tumor Board

Current and future immunotherapeutic approaches in pancreatic cancer treatment

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