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Cancers
Special Issues
Metabolic Reprogramming as an Exploitable Vulnerability in NSCLC
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Metabolic Reprogramming as an Exploitable Vulnerability in NSCLC

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (15 April 2022) | Viewed by 4761

Special Issue Editors

Dr. Massimo Broggini

E-Mail Website
Guest Editor
Laboratory of Molecular Pharmacology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, via G. La Masa 19, 20156 Milan, Italy.
Interests: lung cancer; oncogenes; kras; cancer metabolism; preclinical pharmacology; drug resistance; targeted therapy; transgenic models
Dr. Elisa Caiola

E-Mail Website
Co-Guest Editor
Laboratory of Molecular Pharmacology, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 20156 Milan, Italy.
Interests: non small cell lung cancer; drug combinations; signal transduction; cancer metabolism; organoids; patient-derived xenografts; CRISPR-Cas9 technology

Special Issue Information

Dear Colleague, 

NSCLC still represents one of the most frequent and deadliest cancers in the world. It is a heterogeneous disease, with multiple different oncogenic driver mutations representing potential therapeutic targets. Despite the approval of targeted therapies and immune-checkpoint inhibitors, which significantly improved non small cell lung cancer (NSCLC) patient survival, a significant proportion of patients cannot benefit from these treatments. These include patients with KRAS and LKB1/STK11 mutations. Among NSCLCs, these tumors are among those with the worst prognosis. Both KRAS and LKB1 gene products play a pivotal role in metabolic reprogramming and nutrient sensing. The metabolic alterations present in KRAS/LKB1 mutated NSCLC could, however, represent a vulnerable point of these tumors opening the possibility to combine chemotherapy with drugs interfering with cell metabolism.  

This Special Issue aims to increase the knowledge of the metabolic alterations of these tumors and in optimizing combination treatments which could help in ameliorating the prognosis of this group of NSCLC patients.

Dr. Massimo Broggini
Guest Editor
Dr. Elisa Caiola
Co-Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Cancer metabolism
  • NSCLC
  • KRAS
  • STK11/LKB1 gene
  • Drug combinations
  • Energetic stress

Published Papers (2 papers)

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Editorial

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4 pages, 396 KiB  
Editorial
It’s Got Too Greedy. New Therapeutic Options for Metabolic[ally] Addicted NSCLC?
by Elisa Caiola and Massimo Broggini
Cancers 2020, 12(11), 3223; https://doi.org/10.3390/cancers12113223 - 01 Nov 2020
Viewed by 1531
Abstract
Accounting for more than 2 million new cases and around 1 [...] Full article
(This article belongs to the Special Issue Metabolic Reprogramming as an Exploitable Vulnerability in NSCLC)
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Research

Jump to: Editorial

14 pages, 3046 KiB  
Article
Non-Canonical Role of PDK1 as a Negative Regulator of Apoptosis through Macromolecular Complexes Assembly at the ER–Mitochondria Interface in Oncogene-Driven NSCLC
by Viviana De Rosa, Francesca Iommelli, Cristina Terlizzi, Eleonora Leggiero, Rosa Camerlingo, Giovanna G. Altobelli, Rosa Fonti, Lucio Pastore and Silvana Del Vecchio
Cancers 2021, 13(16), 4133; https://doi.org/10.3390/cancers13164133 - 17 Aug 2021
Cited by 5 | Viewed by 2635
Abstract
Here, we tested whether co-targeting of glucose metabolism and oncogene drivers may enhance tumor response to tyrosine kinase inhibitors (TKIs) in NSCLC. To this end, pyruvate dehydrogenase kinase 1 (PDK1) was stably downregulated in oncogene-driven NSCLC cell lines exposed or not to TKIs. [...] Read more.
Here, we tested whether co-targeting of glucose metabolism and oncogene drivers may enhance tumor response to tyrosine kinase inhibitors (TKIs) in NSCLC. To this end, pyruvate dehydrogenase kinase 1 (PDK1) was stably downregulated in oncogene-driven NSCLC cell lines exposed or not to TKIs. H1993 and H1975 cells were stably transfected with scrambled (shCTRL) or PDK1-targeted (shPDK1) shRNA and then treated with MET inhibitor crizotinib (1 µM), double mutant EGFRL858R/T790M inhibitor WZ4002 (1 µM) or vehicle for 48 h. The effects of PDK1 knockdown on glucose metabolism and apoptosis were evaluated in untreated and TKI-treated cells. PDK1 knockdown alone did not cause significant changes in glycolytic cascade, ATP production and glucose consumption, but it enhanced maximal respiration in shPDK1 cells when compared to controls. When combined with TKI treatment, PDK1 downregulation caused a strong enhancement of OXPHOS and a marked reduction in key glycolytic enzymes. Furthermore, increased levels of apoptotic markers were found in shPDK1 cells as compared to shCTRL cells after treatment with TKIs. Co-immunoprecipitation studies showed that PDK1 interacts with PKM2, Bcl-2 and Bcl-xL, forming macromolecular complexes at the ER–mitochondria interface. Our findings showed that downregulation of PDK1 is able to potentiate the effects of TKIs through the disruption of macromolecular complexes involving PKM2, Bcl-2 and Bcl-xL. Full article
(This article belongs to the Special Issue Metabolic Reprogramming as an Exploitable Vulnerability in NSCLC)
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