Related Experiment Video

Updated: May 8, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

11.0K

Proteogenomic Characterization Reveals Therapeutic Vulnerabilities in Lung Adenocarcinoma

Michael A Gillette1, Shankha Satpathy2, Song Cao3

  • 1Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, 02142, USA; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA, 02115, USA.

Cell
|July 11, 2020
PubMed

Insights

This study comprehensively analyzed lung adenocarcinoma (LUAD) using proteogenomics, revealing four distinct subgroups and identifying therapeutic vulnerabilities. The findings offer new insights into LUAD biology and potential treatment strategies.

Area of Science:

  • Oncology
  • Proteomics
  • Genomics

Background:

  • Lung adenocarcinoma (LUAD) remains a leading cause of cancer death.
  • Understanding LUAD heterogeneity is crucial for developing effective therapies.

Purpose of the Study:

  • To perform comprehensive proteogenomic characterization of LUAD tumors and matched normal adjacent tissues (NATs).
  • To identify novel therapeutic opportunities and biomarkers for LUAD.

Main Methods:

  • Integrated analysis of genomics, epigenomics, proteomics, phosphoproteomics, and acetylproteomics.
  • Multi-omics clustering of 110 LUAD tumors and 101 NATs.
  • Immune subtyping and analysis of smoking-associated LUADs.

Main Results:

  • Identified four LUAD subgroups based on driver mutations, country, and gender.
  • Uncovered therapeutic vulnerabilities linked to KRAS, EGFR, and ALK drivers.
  • Revealed STK11's association with immune-cold tumors and potential immunosuppressive roles of neutrophil degranulation.
  • Detected differentially expressed proteins in NATs with diagnostic and therapeutic potential.

Conclusions:

  • Proteogenomic characterization provides a deeper understanding of LUAD biology and heterogeneity.
  • The study identified actionable therapeutic targets and potential biomarkers for LUAD.
  • The generated dataset serves as a valuable public resource for LUAD research and clinical application.
Keywords:
CPTACacetylationadenocarcinomagenomicslung cancermass spectrometryphosphorylationproteinproteogenomicsproteomics

More Related Videos

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib09:38

Establishment and Characterization of Three Afatinib-resistant Lung Adenocarcinoma PC-9 Cell Lines Developed with Increasing Doses of Afatinib

Published on: June 26, 2019

8.3K
Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids08:52

Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids

Published on: November 22, 2021

4.5K

Related Concept Videos

Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Adaptive Mechanisms in Cancer Cells02:53

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
Pulmonary Hypertension: Classification and Pathogenesis01:30

Pulmonary Hypertension: Classification and Pathogenesis

Pulmonary hypertension (PH) is a severe health condition in which the mean pulmonary arterial pressure increases to 25 mmHg or more, even when the body is at rest. This high pressure in the blood vessels that transport blood from the heart to the lungs can cause various symptoms, including shortness of breath, can lead to right heart failure, and significantly affect the overall quality of life.
There are various classifications for PH, each relating to different underlying causes and also...
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu01:29

Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu

Genetic variations significantly influence drug response through pharmacokinetics, receptor interactions, and biologic milieu modifications. Pharmacokinetic alterations impact drug metabolism and clearance, affecting efficacy and toxicity. Variants in drug-metabolizing enzymes, such as CYP2C9 and CYP2C19, alter drug activation and elimination. For example, CYP2C9 loss-of-function variants require lower warfarin doses to prevent excessive bleeding, while CYP2C19 variants reduce clopidogrel...
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase01:11

Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase

Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
Pharmacogenomics: Identification of New Drug Targets01:29

Pharmacogenomics: Identification of New Drug Targets

Advances in genomics have profoundly influenced drug discovery by increasing both the speed and accuracy of pharmaceutical development. Pharmacogenomics, which examines how genetic variation influences drug response, facilitates the identification of novel therapeutic targets and enables patient stratification for personalized treatment. These strategies contribute to improved drug efficacy, minimized adverse effects, and more efficient clinical trial design.Mapping genetic differences...