NSCLC—Tumor Microenvironment and Metastasis

Dear Colleagues, 

As a leading cause of cancer-related deaths worldwide, lung cancer remains a significant health concern. NSCLC, with its histological and molecular subtypes, represents a truly heterogeneous entity with dismal outcomes. The additional complexity of the tumor microenvironment (TME) further augments this heterogeneity, leading to tumor progression and metastasis.

The interaction of cells and their mediators in the TME plays a crucial role in cancer development. This transition is fueled by the recruitment of stromal cells—specifically, cancer-associated fibroblasts (CAFs). The extracellular matrix (ECM) is important for structural support and also serves as a depot for growth factors and cytokines critical for cell signaling via receptors such as integrins. CAFs facilitate the remodeling of the ECM, yielding a stiffer matrix leading to aberrant signaling through a plethora of growth factors and cytokines critical for cell signaling via receptors such as integrins. The NSCLC TME also harbors immune cells that can create an immunosuppressive ‘cold’ TME, reducing the therapeutic efficacy of immune checkpoint inhibitors. As tumors grow, the TME becomes hypoxic, followed by angiogenesis as an adaptive response to the hypoxia. This angiogenesis is critical for continued tumor growth and metastasis. Hypoxia also plays a pivotal role in shifting tumor metabolism from oxidative phosphorylation to glycolysis, facilitating rapid growth and proliferation.

These various aspects of the TME are in constant crosstalk, each complimenting the other toward the establishment of a favorable environment for tumor expansion. This progression is also critical for the formation of the pre-metastatic niche. Just as the evolving tumor secretes cytokines and other growth factors that recruit various cells into its nascent microenvironment, the TME secretes several factors as well as extracellular vesicles (EVs) that contribute to the formation of the pre-metastatic niche. Based on Paget’s ‘seed and soil’ hypothesis, metastasizing cells demonstrate a preference for specific organ microenvironments. EVs, like exosomes, play a key role in preparing the cell-free environment prior to metastatic seeding. Such diverse contributory factors can lead to matrix remodeling, perturbed immune crosstalk, and dysregulated metabolic flux, thus influencing the metastatic potential of NSCLC to the brain, bone, and liver.

This Special Issue invites authors to contribute their cutting-edge research articles and reviews on the contributions of the TME to the progression and metastasis of NSCLCs, which will ultimately improve therapeutic targeting of this devastating disease.

Dr. Mumtaz Rojiani
Dr. Ravindra Kolhe
Dr. Pankaj Ahluwalia
Guest Editors

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.

• NSCLC
• metastasis
• matrix interaction
• therapeutics