What is the clinical evidence from this study?

Study design: Cross-Sectional. Population: Adrenocortical cancer (ACC) (n=135). Intervention: Molecular profiling. Primary outcome: Frequency of biomarker alterations associated with drug sensitivity and resistance.

What question did this study set out to answer?

To identify predictive biomarkers and actionable molecular targets associated with drug sensitivity and resistance in refractory adrenocortical cancer.

January 1, 2015Biomarkers in CancerOpen Access

Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

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Key result

Molecular profiling of 135 adrenocortical cancer tumors identified frequent biomarker alterations, including loss of ERCC1 (56%) and RRM1 (58%), which may direct targeted therapies.

Why the study?

What are the molecular profiles and potential predictive biomarkers for therapy in refractory adrenocortical cancers?

Population

135 adrenocortical cancer (ACC) tumor samples

Design

Cross-sectional

Authors

SMSherri Z. MillisPHG Foundation SESamuel EjadiUniversity of California, Irvine MDMichael J. DemeureHoag Memorial Hospital Presbyterian

Discussion

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Implication

May support targeted therapy trials in refractory adrenocortical cancer; leaves open clinical utility pending prospective validation.

Key Points

To identify predictive biomarkers and actionable molecular targets associated with drug sensitivity and resistance in refractory adrenocortical cancer.
Analyzed tumor samples from 135 patients with adrenocortical cancer at a single commercial reference laboratory.
Assessed molecular alterations using immunohistochemistry, in situ hybridization (FISH or CISH), and gene sequencing to detect therapy-associated biomarkers.
Protein overexpression associated with chemoresponse included progesterone receptor in 63%, topoisomerase 1 in 46%, topoisomerase 2-alpha in 42%, and PD-L1/PD-1 tumor-infiltrating lymphocytes in >40% of cases.
Loss of key repair and target proteins was observed for MGMT in 71%, PTEN in 59%, RRM1 in 58%, and ERCC1 in 56% of cases.
Targeted gene sequencing revealed mutations in TP53 in 48% of cases and canonical Wnt pathway genes (CTNNB1 or APC) in 35% of cases, with no other recurrent genomic alterations identified.

Study Design

Type

Cross-Sectional (n=135)

Multicenter

Structured PICO

What are the molecular profiles and potential predictive biomarkers for therapy in refractory adrenocortical cancers?

Population

135 adrenocortical cancer tumor samples analyzed for molecular profiling to identify predictive biomarkers.

Exposure

Molecular profiling (immunohistochemistry, in situ hybridization, and/or gene sequencing)

Outcome

Identification of markers associated with drug sensitivity and resistancesurrogate

Molecular profiling of adrenocortical cancers reveals frequent biomarker alterations that could potentially guide targeted therapies and explain resistance to traditional chemotherapy.

Cite This Study

Millis et al. (2015) conducted a cross-sectional in Adrenocortical cancer (ACC) (n=135). Molecular profiling was evaluated on Frequency of biomarker alterations associated with drug sensitivity and resistance. Molecular profiling of 135 adrenocortical cancer tumors identified frequent biomarker alterations, including loss of ERCC1 (56%) and RRM1 (58%), which may direct targeted therapies.

synapsesocial.com/papers/6a99d022ade9b01f3a1d6fea https://doi.org/10.4137/bic.s34292

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Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Molecular Profiling of Refractory Adrenocortical Cancers and Predictive Biomarkers to Therapy

Discussion

Member takes

Implication

Key Points

Study Design

Structured PICO

Cite This Study

Also Consider

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