Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy

Genugten, E.A.J. van; Weijers, Jetty Anne Mina; Heskamp, Sandra; Kneilling, Manfred; Heuvel, Michel M. van den; Piet, Berber; Bussink, Johan; Hendriks, Lizza; Aarntzen, Erik H.J.G.

doi:10.3389/fonc.2021.786089

Cited by 2 publications

(2 citation statements)

References 284 publications

(333 reference statements)

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“…Although most of this discussion has focused on the addition of potential metabolic modulators to concurrent chemoradiation, the use of metabolic imaging is vital for target delineation of current radiation therapy. Molecular imaging in lung cancer has been discussed extensively in these previous reviews ( 161 – 163 ). Fluorodeoxyglucose (FDG)-PET scans are standard of care for the appropriate staging of newly diagnosed patients with NSCLC.…”

Section: Metabolic Imaging and Treatment Modulationmentioning

confidence: 99%

Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer: Where do we go from here?

Dhawan

Pifer²,

Sandulache³

et al. 2022

Front. Oncol.

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In the US, there are ~250,000 new lung cancer diagnoses and ~130,000 deaths per year, and worldwide there are an estimated 1.6 million deaths per year from this deadly disease. Lung cancer is the most common cause of cancer death worldwide, and it accounts for roughly a quarter of all cancer deaths in the US. Non-small cell lung cancer (NSCLC) represents 80-85% of these cases. Due to an enormous tobacco cessation effort, NSCLC rates in the US are decreasing, and the implementation of lung cancer screening guidelines and other programs have resulted in a higher percentage of patients presenting with potentially curable locoregional disease, instead of distant disease. Exciting developments in molecular targeted therapy and immunotherapy have resulted in dramatic improvement in patients’ survival, in combination with new surgical, pathological, radiographical, and radiation techniques. Concurrent platinum-based doublet chemoradiation therapy followed by immunotherapy has set the benchmark for survival in these patients. However, despite these advances, ~50% of patients diagnosed with locally advanced NSCLC (LA-NSCLC) survive long-term. In patients with local and/or locoregional disease, chemoradiation is a critical component of curative therapy. However, there remains a significant clinical gap in improving the efficacy of this combined therapy, and the development of non-overlapping treatment approaches to improve treatment outcomes is needed. One potential promising avenue of research is targeting cancer metabolism. In this review, we will initially provide a brief general overview of tumor metabolism as it relates to therapeutic targeting. We will then focus on the intersection of metabolism on both oxidative stress and anti-tumor immunity. This will be followed by discussion of both tumor- and patient-specific opportunities for metabolic targeting in NSCLC. We will then conclude with a discussion of additional agents currently in development that may be advantageous to combine with chemo-immuno-radiation in NSCLC.

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Section: Metabolic Imaging and Treatment Modulationmentioning

confidence: 99%

Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer: Where do we go from here?

Dhawan

Pifer²,

Sandulache³

et al. 2022

Front. Oncol.

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“…Alterations in the tumor environmental metabolic characteristics also affect treatment outcomes ( 15 ). The determination of the abscopal effect helps pave the way for combinations of RT with immunotherapy ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

Insight of a Metabolic Prognostic Model to Identify Tumor Environment and Drug Vulnerability for Lung Adenocarcinoma

et al. 2022

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Metabolic reprogramming is a novel method for the treatment of malignant tumors. The exploration of metabolism procedures between radiosensitive and radioresistant tumors may provide novel perspectives for lung adenocarcinoma (LUAD) patients after radiation therapy. In our study, metabolic reprogramming and immune response changes were found between radioresistant cell line (A549RR) and its parent cells (A549) using gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. Nucleotide/amino acid, lipid, and glucose metabolic process, including Alanine, aspartate and glutamate metabolism, Tryptophan/Tyrosine metabolism, Butanoate metabolism, Purine/Pyrimidine metabolism, were screened out. Then molecular signatures database and The Cancer Genome Atlas Program (TCGA) lung adenocarcinoma datasets were used to identify metabolism-related genes (MRGs) between radiosensitive and radioresistant lung adenocarcinoma (LUAD) cells. A metabolism-based prognostic model, receiver operating characteristic (ROC) curve and nomogram were constructed using Metabolism Score calculated by 14 metabolism-related genes (MRGs). Three independent public datasets, (GSE72094, GSE3141, GSE8894) and one immunotherapy cohort (IMvigor210) were used as external validation cohorts. Expression of 14 hub genes in cells, normal and LUAD specimens were explored by Human Protein Atlas, TIMER2.0 and RT-qPCR. Patients with low-Metabolism Scores were correlated with longer survival times, higher response rates to immune checkpoint inhibitors (ICIs), different immune cell infiltrations and drug vulnerability. Our study demonstrated a comprehensive landscape between radiosensitive and radioresistant LUAD, and provide novel targets for NSCLC, especially those patients received radiation therapy. Moreover, this metabolism-based prognostic model may help to investigate connections between radiosensitivity, immune response, metabolic reprogramming, and patients’ prognosis.

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Imaging the Rewired Metabolism in Lung Cancer in Relation to Immune Therapy

Cited by 2 publications

References 284 publications

Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer: Where do we go from here?

Metabolic targeting, immunotherapy and radiation in locally advanced non-small cell lung cancer: Where do we go from here?

Insight of a Metabolic Prognostic Model to Identify Tumor Environment and Drug Vulnerability for Lung Adenocarcinoma

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