An Overview of Lung Cancer in Women and the Impact of Estrogen in Lung Carcinogenesis and Lung Cancer Treatment

Frontiers in Medicine ◽

10.3389/fmed.2021.600121 ◽

2021 ◽

Vol 8 ◽

Author(s):

Vianey Rodriguez-Lara ◽

Maria Rosa Avila-Costa

Keyword(s):

Lung Cancer ◽

Lung Adenocarcinoma ◽

Cancer Treatment ◽

Critical Role ◽

Lung Carcinogenesis ◽

Lung Cancer Treatment ◽

Incidence And Mortality ◽

Menopausal Women ◽

The Impact

Lung cancer incidence and mortality have significantly increased in women worldwide. Lung adenocarcinoma is the most common form of lung cancer globally. This type of lung cancer shows differences by sex, including the mutational burden, behavior, clinical characteristics, and response to treatment. The effect of sex on lung cancer patients' survival is still controversial; however, lung adenocarcinoma is considered a different disease in women and men. Moreover, lung adenocarcinoma is strongly influenced by estrogen and is also different depending on the hormonal status of the patient. Young pre-menopausal women have been explored as an independent group. They presented in more advanced stages at diagnosis, exhibited more aggressive tumors, and showed poor survival compared to men and post-menopausal women, supporting the role of sex hormones in this pathology. Several reports indicate the estrogen's role in lung carcinogenesis and tumor progression. Thus, there are currently some clinical trials testing the efficacy of antihormonal therapy in lung cancer treatment. This mini review shows the updated data about lung cancer in women, its characteristics, the etiological factors that influence carcinogenesis, and the critical role of estrogen in lung cancer and treatment.

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Role of the Glutathione Metabolic Pathway in Lung Cancer Treatment and Prognosis: A Review

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.7110 ◽

2006 ◽

Vol 24 (11) ◽

pp. 1761-1769 ◽

Cited By ~ 81

Author(s):

Ping Yang ◽

Jon O. Ebbert ◽

Zhifu Sun ◽

Richard M. Weinshilboum

Keyword(s):

Lung Cancer ◽

Drug Resistance ◽

Treatment Outcome ◽

Cancer Treatment ◽

Metabolic Pathway ◽

Drug Efficacy ◽

Glutathione System ◽

Lung Cancer Treatment ◽

The Impact

Inherent and acquired drug resistance is a cause of chemotherapy failure, and pharmacogenomic studies have begun to define gene variations responsible for varied drug metabolism, which influences drug efficacy. Platinum-based compounds are the most commonly used chemotherapeutic agents in the treatment of advanced stage lung cancer patients, and the glutathione metabolic pathway is directly involved in the detoxification or inactivation of platinum drugs. Consequently, genotypes corresponding to higher drug inactivation enzyme activity may predict poor treatment outcome. Available evidence is consistent with this hypothesis, although a definitive role for glutathione system genes in lung cancer prognosis needs to be elucidated. We present evidence supporting a role of the glutathione system in acquired and inherited drug resistance and/or adverse effects through the impact of either drug detoxification or drug inactivation, thus adversely effecting lung cancer treatment outcome. The potential application of glutathione system polymorphic genetic markers in identifying patients who may respond favorably, selecting effective antitumor drugs, and balancing drug efficacy and toxicity are discussed.

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Differential Impacts of Insulin-Like Growth Factor-Binding Protein-3 (IGFBP-3) in Epithelial IGF-Induced Lung Cancer Development

Endocrinology ◽

10.1210/en.2010-0693 ◽

2011 ◽

Vol 152 (6) ◽

pp. 2164-2173 ◽

Cited By ~ 13

Author(s):

Woo-Young Kim ◽

Mi-Jung Kim ◽

Hojin Moon ◽

Ping Yuan ◽

Jin-Soo Kim ◽

...

Keyword(s):

Lung Cancer ◽

Lung Tumor ◽

Binding Protein ◽

Cancer Development ◽

Lung Carcinogenesis ◽

Tobacco Carcinogen ◽

Igf I ◽

The Impact ◽

Igfbp 3

The IGF axis has been implicated in the risk of various cancers. We previously reported a potential role of tissue-derived IGF in lung tumor formation and progression. However, the role of IGF-binding protein (IGFBP)-3, a major IGFBP, on the activity of tissue-driven IGF in lung cancer development is largely unknown. Here, we show that IGF-I, but not IGF-II, protein levels in non-small-cell lung cancer (NSCLC) were significantly higher than those in normal and hyperplastic bronchial epithelium. We found that IGF-I and IGFBP-3 levels in NSCLC tissue specimens were significantly correlated with phosphorylated IGF-IR (pIGF-IR) expression. We investigated the impact of IGFBP-3 expression on the activity of tissue-driven IGF-I in lung cancer development using mice carrying lung-specific human IGF-I transgene (Tg), a germline-null mutation of IGFBP-3, or both. Compared with wild-type (BP3+/+) mice, mice carrying heterozygous (BP3+/−) or homozygous (BP3−/−) deletion of IGFBP-3 alleles exhibited decreases in circulating IGFBP-3 and IGF-I. Unexpectedly, IGFTg mice with 50% of physiological IGFBP-3 (BP3+/−; IGFTg) showed higher levels of pIGF-IR/IR and a greater degree of spontaneous or tobacco carcinogen [4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone]-induced lung tumor development and progression than did the IGFTg mice with normal (BP3+/+;IGFTg) or homozygous deletion of IGFBP-3 (BP3−/−; IGFTg). These data show that IGF-I is overexpressed in NSCLC, leading to activation of IGF-IR, and that IGFBP-3, depending on its expression level, either inhibits or potentiates IGF-I actions in lung carcinogenesis.

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Imaging Biomarkers of Tumour Proliferation and Invasion for Personalised Lung Cancer Therapy

Journal of Personalized Medicine ◽

10.3390/jpm10040222 ◽

2020 ◽

Vol 10 (4) ◽

pp. 222

Author(s):

Loredana G. Marcu

Keyword(s):

Lung Cancer ◽

Cancer Therapy ◽

Cancer Treatment ◽

Critical Role ◽

Imaging Biomarkers ◽

Lung Cancer Treatment ◽

Cancer Management ◽

Specificity And Sensitivity ◽

Lung Cancer Therapy ◽

Tumour Proliferation

Personalised treatment in oncology has seen great developments over the last decade, due to both technological advances and more in-depth knowledge of radiobiological processes occurring in tumours. Lung cancer therapy is no exception, as new molecular targets have been identified to further increase treatment specificity and sensitivity. Yet, tumour resistance to treatment is still one of the main reasons for treatment failure. This is due to a number of factors, among which tumour proliferation, the presence of cancer stem cells and the metastatic potential of the primary tumour are key features that require better controlling to further improve cancer management in general, and lung cancer treatment in particular. Imaging biomarkers play a key role in the identification of biological particularities within tumours and therefore are an important component of treatment personalisation in radiotherapy. Imaging techniques such as PET, SPECT, MRI that employ tumour-specific biomarkers already play a critical role in patient stratification towards individualized treatment. The aim of the current paper is to describe the radiobiological challenges of lung cancer treatment in relation to the latest imaging biomarkers that can aid in the identification of hostile cellular features for further treatment adaptation and tailoring to the individual patient’s needs.

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Prognostic Factors and Biomarkers of Responses to Immune Checkpoint Inhibitors in Lung Cancer

International Journal of Molecular Sciences ◽

10.3390/ijms20194931 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4931 ◽

Cited By ~ 13

Author(s):

Andrea Bianco ◽

Fabio Perrotta ◽

Giusi Barra ◽

Umberto Malapelle ◽

Danilo Rocco ◽

...

Keyword(s):

Lung Cancer ◽

T Cell ◽

Cancer Treatment ◽

Immune Checkpoint ◽

Immune Checkpoint Inhibitors ◽

Checkpoint Inhibitors ◽

T Cell Subsets ◽

Durable Response ◽

Lung Cancer Treatment ◽

The Impact

Manipulation of the immune response is a game changer in lung cancer treatment, revolutionizing management. PD1 and CTLA4 are dynamically expressed on different T cell subsets that can either disrupt or sustain tumor growth. Monoclonal antibodies (MoAbs) against PD1/PDL1 and CTLA4 have shown that inhibitory signals can be impaired, blocking T cell activation and function. MoAbs, used as both single-agents or in combination with standard therapy for the treatment of advanced non-small cell lung cancer (NSCLC), have exhibited advantages in terms of overall survival and response rate; nivolumab, pembrolizumab, atezolizumab and more recently, durvalumab, have already been approved for lung cancer treatment and more compounds are in the pipeline. A better understanding of signaling elicited by these antibodies on T cell subsets, as well as identification of biological determinants of sensitivity, resistance and correlates of efficacy, will help to define the mechanisms of antitumor responses. In addition, the relevance of T regulatory cells (Treg) involved in immune responses in cancer is attracting increasing interest. A major challenge for future research is to understand why a durable response to immune checkpoint inhibitors (ICIs) occurs only in subsets of patients and the mechanisms of resistance after an initial response. This review will explore current understanding and future direction of research on ICI treatment in lung cancer and the impact of tumor immune microenvironment n influencing clinical responses.

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