bims-meluca 2022-02-20 papers

Cells. 2022 Jan 25. pii: 413. [Epub ahead of print]11(3):

Reprogramming of Lipid Metabolism in Lung Cancer: An Overview with Focus on EGFR-Mutated Non-Small Cell Lung Cancer.

Kamal Eltayeb, Silvia La Monica, Marcello Tiseo, Roberta Alfieri, Claudia Fumarola.

Lung cancer is the leading cause of cancer deaths worldwide. Most of lung cancer cases are classified as non-small cell lung cancers (NSCLC). EGFR has become an important therapeutic target for the treatment of NSCLC patients, and inhibitors targeting the kinase domain of EGFR are currently used in clinical settings. Recently, an increasing interest has emerged toward understanding the mechanisms and biological consequences associated with lipid reprogramming in cancer. Increased uptake, synthesis, oxidation, or storage of lipids has been demonstrated to contribute to the growth of many types of cancer, including lung cancer. In this review, we provide an overview of metabolism in cancer and then explore in more detail the role of lipid metabolic reprogramming in lung cancer development and progression and in resistance to therapies, emphasizing its connection with EGFR signaling. In addition, we summarize the potential therapeutic approaches targeting lipid metabolism for lung cancer treatment.

Keywords: EGFR; EGFR-TKI resistance; lipid metabolism; lung cancer

DOI: https://doi.org/10.3390/cells11030413

J Clin Lab Anal. 2022 Feb 18. e24300

Prognostic value of prognostic nutritional index and its variations in advanced non-small-cell lung cancer patients treated with anlotinib monotherapy.

Tian Chen, Gaofeng Liang, Zhenfei Xiang, Jinxian He, Xiaoyu Xu, Mengqiu Tang.

BACKGROUND: Anlotinib is a third-line or further therapy for advanced non-small-cell lung cancer (NSCLC). However, the lack of simple biomarkers to predict the curative effect of anlotinib creates significant unmet needs in exploring the markers. This study aimed to explore the relationship between the prognostic nutritional index (PNI) and its variations and efficacy of anlotinib.METHODS: Data for patients with advanced NSCLC who received anlotinib were collected at Ningbo Medical Center Lihuili Hospital. The data included the values of pretreatment PNI (pre-PNI), posttreatment PNI (post-PNI), and ΔPNI (post-PNI minus the pre-PNI). The Kaplan-Meier method was used to generate survival curves, whereas univariate and multivariate Cox regression analyses were used to analyze survival predictors.
RESULTS: A high disease control rate was associated with a high pre-PNI (p = 0.007), high post-PNI (p = 0.000), and high ΔPNI (p = 0.006). Univariable analysis revealed that pre-PNI ≤41.80, post-PNI ≤42.48, and ΔPNI ≤0.20 were significant risk factors for poor survival. According to the multivariate analysis, progression-free survival (PFS) in patients with post-PNI ≤42.48 was significantly shorter than in patients with higher values (median PFS: 1.5 months vs. 4.0 months, p = 0.010).
CONCLUSIONS: Pre-PNI, ΔPNI, and post-PNI were found to be predictive factors for response in advanced NSCLC patients treated with anlotinib as a third-line or further treatment. Only post-PNI was a reliable predictor of PFS. Therefore, PNI and its variations, particularly post-PNI, are affordable and accessible predictors of NSCLC patients treated with anlotinib in clinical work.

Keywords: anlotinib; non-small-cell lung cancer; prognostic factor; prognostic nutritional index; treatment response

DOI: https://doi.org/10.1002/jcla.24300

Cureus. 2022 Jan;14(1): e21078

Unraveling the Role of STK11/LKB1 in Non-small Cell Lung Cancer.

Vikram Sumbly, Ian Landry.

There are two major groups of lung cancer: non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLCs can be further separated into three different categories: lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Pulmonary adenocarcinomas represent nearly half of all lung cancer cases and are known to be caused by smoking, certain occupational exposures, and specific genetic mutations. Scientists have noticed that most NSCLCs are driven by defects in the following genes: EGFR, BRAF, ALK, MET, and HER. Abnormalities in the STK11/LKB1 gene have also been shown to induce lung adenocarcinoma. LKB1-deficient cancer cells contain an overactive AMPK "energy sensor," which inhibits cellular death and promotes glucose, lipid, and protein synthesis via the mTOR protein complex. Studies have also discovered that the loss of STK11/LKB1 favors oncogenesis by creating an immunosuppressive environment for tumors to grow and accelerate events such as angiogenesis, epithelial-mesenchymal transition (EMT), and cell polarity destabilization. STK11/LKB1-mutant lung cancers are currently treated with radiotherapy with or without chemotherapy. Recent clinical trials studying the effects of glutaminase inhibitors, mTOR inhibitors, and anti-PD-L1 therapy in lung cancer patients have yielded promising results. This narrative review provides an overview of the STK11/LKB1 gene and its role in cancer development. Additionally, a summary of the LKB1/APMK/mTOR is provided.

Keywords: lkb1/ampk/mtor; lung cancer; oncology; pathophysiology; stk11/lkb1

DOI: https://doi.org/10.7759/cureus.21078

Arch Med Sci. 2022 ;18(1): 141-152

The role of statins in lung cancer.

Fatemeh Amin, Farzaneh Fathi, Željko Reiner, Maciej Banach, Amirhossein Sahebkar.

Lung cancer is one of the most common causes of cancer-related mortality in the 21st century. Statins as inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A reductase not only reduce the cholesterol levels in the blood and decrease the risk of cardiovascular disease but may also play an important role in the prevention and treatment of lung cancer. Statins have several antitumor properties including the ability to reduce cell proliferation and angiogenesis, decrease invasion and synergistic suppression of lung cancer progression. Statins induce tumor cell apoptosis by inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac, which are dependent on isoprenylation. Statins reduce angiogenesis in tumors by down-regulation of pro-angiogenic factors, such as vascular endothelial growth factor. In this review, the feasibility and efficacy of statins in the prevention and treatment of lung cancer are discussed.

Keywords: apoptosis; lung cancer; non-small cell lung cancer; statins

DOI: https://doi.org/10.5114/aoms/123225

J Immunother Cancer. 2022 Feb;pii: e004374. [Epub ahead of print]10(2):

Prognostic effect of body mass index in patients with advanced NSCLC treated with chemoimmunotherapy combinations.

INTRODUCTION: It has been recognized that increasing body mass index (BMI) is associated with improved outcome from immune checkpoint inhibitors (ICIs) in patients with various malignancies including non-small cell lung cancer (NSCLC). However, it is unclear whether baseline BMI may influence outcomes from first-line chemoimmunotherapy combinations.METHODS: In this international multicenter study, we evaluated the association between baseline BMI, progression-free survival (PFS) and overall survival (OS) in a cohort of patients with stage IV NSCLC consecutively treated with first-line chemoimmunotherapy combinations. BMI was categorized according to WHO criteria.
RESULTS: Among the 853 included patients, 5.3% were underweight; 46.4% were of normal weight; 33.8% were overweight; and 14.5% were obese. Overweight and obese patients were more likely aged ≥70 years (p=0.00085), never smokers (p<0.0001), with better baseline Eastern Cooperative Oncology Group-Performance Status (p=0.0127), and had lower prevalence of central nervous system (p=0.0002) and liver metastases (p=0.0395). Univariable analyses showed a significant difference in the median OS across underweight (15.5 months), normal weight (14.6 months), overweight (20.9 months), and obese (16.8 months) patients (log-rank: p=0.045, log rank test for trend: p=0.131), while no difference was found with respect to the median PFS (log-rank for trend: p=0.510). Neither OS nor PFS was significantly associated with baseline BMI on multivariable analysis.
CONCLUSIONS: In contrast to what was observed in the context of chemotherapy-free ICI-based regimens, baseline BMI does not affect clinical outcomes from chemoimmunotherapy combinations in patients with advanced NSCLC.

Keywords: immunity; lung neoplasms; metabolic networks and pathways; programmed cell death 1 receptor

DOI: https://doi.org/10.1136/jitc-2021-004374