Lung Cancer Introduction

 Introduction

Lung. Cancer Introduction

Extracellular vesicles (EVs) are lipid bilayer-enclosed extracellular structures which can be formed by outward budding of the plasma membrane or by an intracellular endocytic trafficking pathway involving fusion of multivesicular late endocytic compartments with the plasma membrane. 

These fusion events result in the extracellular release of the intraluminal vesicles of these compartments, generating a subtype of EVs termed ‘exosomes’ [1]. 

Information transmission between tumor cells and various cells in the microenvironment plays an important role in tumor metastasis, and exosomes are one of the important mediums of intercell communication [1, 2].

 Exosomes are vesicles with a diameter of 30–100 nm secreted by different types of cells [3]. 

They carry many kinds of substances, such as lipids, nucleic acids, and proteins, and are widely distributed in body fluids, including urine, plasma, lavage fluid, serosal effusion, and cerebrospinal fluid [4].

 Exosomes have important roles in multiple physiological and pathological processes, exerting biological functions. On the one hand, they are necessary to maintain normal physiological responses. On the other hand, in the pathological state, especially in the tumor environment, they promote carcinogenesis, proliferation, migration, invasion, immunosuppression, and angiogenesis as well as reshape the microenvironment [5].

In recent years, the study of exosomes in tumor has received enormous interest.

 Exosomes contain bio-macromolecules to participate in information exchange between cells [6]. 

They can increase the invasion ability of tumor cells and promote tumor metastasis, which has become a research hotspot in the field of cancer recently [7, 8]. 

Different types of tumor cells secrete different exosome contents. Additionally, factors affecting cell homeostasis, such as a hypoxic microenvironment, survival pressure, and chemotherapy drugs, induces tumor cells to secrete exosomes [9, 10]. 

Therefore, the volume of exosomes secreted by tumors is much higher than that of normal cells. Although the role of most exosomal compounds in cancer is unclear, previous studies have shown that tumor-derived exosomes promote tumor growth and metastasis by inducing epithelial–mesenchymal transformation (EMT) of tumor cells.

 They also promote angiogenesis, the transformation of cancer-associated fibroblasts, immunosuppression, and formation of a premetastatic microenvironment by acting on stromal cells in the microenvironment [11–15].

Several studies have shown that differential expression of exosome contents is closely related to lung cancer metastasis, playing an important role in the multilink and multistep process [16, 17].

 The multiple mechanisms of tumor-derived exosomes promoting cancer metastasis are mainly summarized in Fig. 1.

 The abscission of cancer cells is essentially a manifestation of increased migration and invasion of tumor cells. Compared with those in healthy people, exosomes are more abundant in circulating body fluids of patients with lung cancer. 

A number of studies have found that exosomes promote the occurrence and development of lung cancer by promoting the formation of the lung cancer microenvironment, 

increasing the ability of tumor cell invasion and metastasis, mediating tumor immunosuppression, and participating in chemo-radiotherapy resistance [18].

 The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis. Therefore, in this article, the relevant research status of the role of exosomes in lung cancer migration and invasion, immunosuppression and escape, angiogenesis, and other processes is reviewed.

Fig. 1.

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Tumor-derived exosomes promote cancer metastasis. Tumor-derived exosomes through multiple mechanisms participate in cancer metastasis by reshaping the tumor microenvironment; promoting cellular epithelial–mesenchymal transformation (EMT); promoting cell proliferation, inhabiting apoptosis; immunosuppression; promoting hematogenous metastasis and angiogenesis of metastasitic tumor to promote cancer metastasis

Ref

Mol Cancer. 2021 Sep 13;20:117. doi: 10.1186/s12943-021-01411-w

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms

Chunyang Jiang 1,✉, Na Zhang 2, Xiaoli Hu 3, Hongyan Wang 4,✉

Lung cancer (Tumour exosomes ,,Metastasis)

 

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms 

 Metastasis is the spread of cancer cells from their original location to other parts of the body. 

Exosomes are 40–160 nm extracellular vesicles produced by cancer cells (tumor-derived exosomes) that facilitate tumor progression, metastasis, angiogenesis, and immune evasion. 

Angiogenesis is the physiological process of forming new capillary blood vessels from pre-existing vasculature, 

Abstract

As an important medium of intercellular communication, exosomes play an important role in information transmission between tumor cells and their microenvironment. 

Tumor metastasis is a serious influencing factor for poor treatment effect and shortened survival. 

Lung cancer is a major malignant tumor that seriously threatens human health.

 The study of the underlying mechanisms of exosomes in tumor genesis and development may provide new ideas for early and effective diagnosis and treatment of lung cancer metastasis.

 Many studies have shown that tumor-derived exosomes promote lung cancer development through a number of processes. 

By promoting epithelial–mesenchymal transition of tumor cells, they induce angiogenesis, establishment of the pretransfer microenvironment, and immune escape. 

This understanding enables researchers to better understand the mechanism of lung cancer metastasis and explore new treatments for clinical application.

 In this article, we systematically review current research progress of tumor-derived exosomes in metastasis of lung cancer. 

Although positive progress has been made toward understanding the mechanism of exosomes in lung cancer metastasis, systematic basic research and clinical translational research remains lacking and are needed to translate our scientific understanding toward applications in the clinical diagnosis and treatment of lung cancer metastasis in th,✉,✉e near future.

Ref

. 2021 Sep 13;20:117. doi: 10.1186/s12943-021-01411-w

Tumor-associated exosomes promote lung cancer metastasis through multiple mechanisms

Chunyang Jiang ^1,✉, Na Zhang ², Xiaoli Hu ³, Hongyan Wang ^4,✉

 वायु प्रदूषण आणि फुफ्फुसांचा कर्करोग

संदर्भ

Curr Environ Health Rep. 2023 Dec 6;10(4):478–489. doi: 10.1007/s40572-023-00421-8

वायु प्रदूषण आणि फुफ्फुसांचा कर्करोग: रोगजनक यंत्रणा आणि क्लिनिकल उपयुक्तता म्हणून एक्स्ट्रासेल्युलर वेसिकल्सचे योगदान

जोनाथन गोन्झालेझ-रुइझ १, अँड्रिया ए. बकारेली २, डेव्हिड कांतू-डी-लिओन १, डिडियर प्राडा ३

प्रस्तावना

अलीकडच्या वर्षांत, मानवी आरोग्यावर वायुप्रदूषणाचे होणारे प्रतिकूल परिणाम जगभरात चिंतेचा विषय बनले आहेत [१, २].

आपण श्वास घेत असलेल्या हवेची गुणवत्ता आपले आरोग्य राखण्यात, विशेषतः फुफ्फुसांच्या आरोग्याच्या बाबतीत, महत्त्वपूर्ण भूमिका बजावते [३].

वायुप्रदूषकांना दीर्घकाळ संपर्क आल्याने खोकला, घरघर, श्वास लागणे आणि छातीत घट्टपणा यांसारखी विविध प्रकारची श्वसन लक्षणे दिसू शकतात, जी सर्व तीव्र आणि दीर्घकालीन परिणामांशी संबंधित आहेत [४].

हानिकारक कण आणि वायूंच्या जटिल मिश्रणाने बनलेल्या वायुप्रदूषकांचा संबंध दमा, क्रॉनिक ऑब्स्ट्रक्टिव्ह पल्मोनरी डिसीज (COPD), फुफ्फुसांची कार्यक्षमता कमी होणे आणि फुफ्फुसांचा कर्करोग यासह विविध प्रकारच्या श्वसन विकारांशी जोडला गेला आहे,

विशेषतः, नॉन-स्मॉल सेल लंग कॅन्सर (NSCLC) [५]. पर्यावरणीय वायुप्रदूषक आणि फुफ्फुसांचा कर्करोग यांच्यातील संबंधाचा सखोल अभ्यास करण्यात आला आहे [३].

ऑक्टोबर २०१३ मध्ये, जागतिक आरोग्य संघटनेच्या कर्करोगावरील विशेष संस्थेने, म्हणजेच इंटरनॅशनल एजन्सी फॉर रिसर्च ऑन कॅन्सर (IARC) ने जाहीर केले की बाह्य वायू प्रदूषण मानवांसाठी कर्करोगजन्य (गट १) म्हणून वर्गीकृत केले गेले आहे [६].

पुढील महामारीविज्ञान अभ्यासांनी वायू प्रदूषकांच्या दीर्घकाळ संपर्कात राहणे आणि फुफ्फुसाच्या कर्करोगाचा विकास यांच्यात एक मजबूत संबंध सातत्याने दर्शविला आहे [७].

फुफ्फुसाचा कर्करोग हा सर्वात प्रचलित कर्करोग आहे आणि तो कर्करोगाशी संबंधित मृत्यूंचे प्रमुख कारण आहे, तसेच ही एक महत्त्वपूर्ण जागतिक आरोग्य समस्या आहे,

ज्याची व्याप्ती सध्याची जागतिक आकडेवारी दर्शवते. जगभरात, फुफ्फुसाचा कर्करोग हा सर्वात सामान्य कर्करोग आहे आणि त्याचा प्रभाव लक्षणीय आहे.

२०२२ मध्ये, फुफ्फुसाच्या कर्करोगाची २० लाखांहून अधिक नवीन प्रकरणे नोंदवली गेली, जी सर्व नवीन कर्करोगाच्या निदानांपैकी अंदाजे ११% होती [८].

g in the lungs [23].वायू प्रदूषणाच्या वायूंमध्ये नायट्रोजन ऑक्साईड (NOx: NO आणि NO2) आणि सल्फर डायऑक्साइड (SO2) यांचा समावेश होतो, जे प्रामुख्याने ज्वलन प्रक्रियेतून तयार होतात, जसे की वाहनांच्या इंजिनमध्ये, ऊर्जा प्रकल्पांमध्ये आणि औद्योगिक सुविधांमध्ये [24]. हे प्रदूषक वातावरणातील इतर संयुगांशी अभिक्रिया करून नायट्रिक ॲसिड (HNO3) आणि ओझोन (O3) सारखे दुय्यम प्रदूषक तयार करू शकतात [25].

अभ्यासातून असे दिसून आले आहे की, नायट्रोजन ऑक्साईडच्या संपर्कात आल्याने, विशेषतः इतर प्रदूषकांसोबत, फुफ्फुसाच्या कर्करोगाचा धोका वाढतो [26].

O3, जो प्रकाशरासायनिक धुराचा एक प्रमुख घटक आहे, हे आणखी एक महत्त्वाचे वायू प्रदूषक आहे जे सूर्यप्रकाशाच्या उपस्थितीत नायट्रोजन ऑक्साईडची अस्थिर सेंद्रिय संयुगांशी (VOCs) अभिक्रिया होऊन तयार होते [27].

ओझोनच्या दीर्घकाळ संपर्कात राहण्याचा संबंध श्वसनसंस्थेवरील प्रतिकूल परिणामांशी जोडला गेला आहे, आणि अलीकडील संशोधनात ओझोनच्या संपर्कात येणे आणि फुफ्फुसाच्या कर्करोगाचा विकास यांच्यात संभाव्य संबंध असल्याचेही सूचित केले आहे [28].

अस्थिर सेंद्रिय संयुगे देखील वायू प्रदूषणात उपस्थित असतात आणि ती औद्योगिक प्रक्रिया, वाहनांमधून होणारे उत्सर्जन आणि विद्रावक (solvents) यासह विविध स्रोतांमधून उत्सर्जित होतात [29].

बेंझिन, फॉर्मल्डिहाइड आणि 1,3-ब्युटाडाइन यांसारख्या काही VOCs चे IARC द्वारे कर्करोगजन्य पदार्थ म्हणून वर्गीकरण केले गेले आहे [30].

ही सर्व प्रदूषके पेशी आणि ऊतींमध्ये स्वतंत्रपणे तसेच मिश्रणाच्या स्वरूपात कार्य करू शकतात. त्यामुळे, वायू प्रदूषणामध्ये विविध संयुगांचा समावेश असतो, जी दीर्घकाळ संपर्कात राहिल्यास फुफ्फुसाच्या कर्करोगाचा, विशेषतः नॉन-स्मॉल सेल फुफ्फुसाच्या कर्करोगाचा (NSCLC) धोका वाढण्यास हातभार लावू शकतात [31].

वायू प्रदूषण आणि फुफ्फुसाच्या कर्करोगाचा विकास: नुकसानीच्या संभाव्य यंत्रणा आणि EVs चे महत्त्व

फुफ्फुसाच्या कर्करोगास कारणीभूत ठरू शकणाऱ्या अनेक यंत्रणा वायू प्रदूषकांमुळे, स्वतंत्रपणे आणि मिश्रणाच्या स्वरूपात, सक्रिय होतात.

फुफ्फुसाच्या कर्करोगास हातभार लावणाऱ्या सर्वात अभ्यासलेल्या घटकांमध्ये कमी-तीव्रतेची, दीर्घकालीन जळजळ, ऑक्सिडेटिव्ह ताण, थेट उत्परिवर्तन, एपिजेनेटिक बदल आणि माइटोकॉन्ड्रियल व एंडोथेलियल बिघड यांचा समावेश आहे, परंतु इतरही अनेक घटक आहेत. EVs यापैकी काही यंत्रणांमध्ये योगदान देऊन इतर पेशींपर्यंत संकेत पोहोचवू शकतात आणि वायू प्रदूषणाच्या नुकसानीशी जुळवून घेण्यासही मदत करू शकतात. वायू प्रदूषण-संबंधित नुकसान आणि EVs च्या भूमिकेचा सारांश आकृती 1 मध्ये दर्शविला आहे

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Air pollution and Lung Cancer

Ref

Curr Environ Health Rep. 2023 Dec 6;10(4):478–489. doi: 10.1007/s40572-023-00421-8

Air Pollution and Lung Cancer: Contributions of 

Extracellular Vesicles as Pathogenic Mechanisms and Clinical Utility

Jonathan González-Ruíz 1, Andrea ABaccarelli 2, David Cantu-de-Leon 1, Diddier Prada3

Introduction

In recent years, the adverse effects of air pollution on human health have become a growing concern worldwide [1, 2]. 

The quality of the air we breathe plays a crucial role in maintaining our well-being, particularly when it comes to lung health [3]. 

Prolonged exposure to air pollutants may induce a wide range of respiratory symptoms, including coughing, wheezing, shortness of breath, and chest tightness, all of them linked with acute and long-term effects [4].

 Air pollutants, consisting of a complex mixture of harmful particles and gases, have been linked to a wide range of respiratory disorders, including asthma, chronic obstructive pulmonary disease (COPD), reduced lung function, and lung cancer,

 in particular, non-small cell lung cancer (NSCLC) [5]. The association between environmental air pollutants and lung cancer has been extensively studied [3].

 In October 2013, the specialized cancer agency of the World Health Organization, the International Agency for Research on Cancer (IARC) announced that outdoor air pollution was classified as carcinogenic to humans (Group 1) [6].

 Further epidemiological studies have consistently demonstrated a strong link between prolonged exposure to air pollutants and the development of lung cancer [7].

Lung cancer ranks as the most prevalent cancer and remains the primary cause of cancer-related deaths and is a significant global health issue,

 with current worldwide statistics reflecting its magnitude. Across the globe, lung cancer stands as the most common cancer, and its impact is substantial.

 In 2022, there were over 2 million new cases of lung cancer reported, accounting for approximately 11% of all new cancer diagnoses [8].

 Unfortunately, lung cancer continues to be the leading cause of cancer-related deaths globally. While this cancer affects both men and women, the statistics reveal significant sex disparities.

 Among men, lung cancer remains the leading cause of cancer-related mortality. 

Among women, it ranks second only to breast cancer, being a major cause of mortality among them.

 These statistics underscore the importance of understanding both the overall prevalence of lung cancer and the gender-specific differences in its incidence and consequences [9].

 It is also the third most common cancer, following breast and colorectal cancers, and the second leading cause of cancer death after breast cancer among women vulnerable groups around the world include individuals with limited access to healthcare, low socioeconomic status, heavy tobacco user, and those living in highly polluted areas [10].

Air pollution may activate several cellular, molecular, and systemic changes, including inflammation, oxidative damage, microthrombosis, epigenomic changes, and activation of several other cellular responses, including the release of extracellular vesicles (EVs) [11••].

 EVs encompass a heterogeneous group of vesicles that can be classified into three main subtypes, microvesicles, exosomes, and apoptotic bodies [12].

 EVs are membrane-bound structures that are shed from the plasma membrane of cells [13]. They encapsulate a diverse range of molecules, including peptides, nucleic acids (such as microRNAs, mRNAs, and long noncoding RNAs), lipids, and metabolites. This cargo can be transferred to recipient cells, modulating their function and behavior [14].

 In normal cells, EVs play an important role in intercellular communication by allowing cells to exchange information and signals with each other [15]. EVs have been shown to be involved in a variety of physiological and pathological processes, including immune regulation, tissue repair and regeneration, inflammation, and angiogenesis [16]. EVs can be released practically by any cell, including cancer cells [17], and have been implicated in tumor growth, metastasis, and drug resistance [18]. This review examines the mechanisms of air pollution’s impact on lung cancer development, with a focus on the contribution of extracellular vesicles to carcinogenesis and cancer progression. Additionally, it explores the potential utility of these vesicles in clinical settings for lung cancer (i.e., NSCLC).

Air Pollution and Its Impact on Human Health

Air pollution components contain particulate matter (PM) and gases, including volatile organic compounds. 

Particulate matter is a common component of air pollution and consists of tiny particles suspended in the air [19].

 These particles can be classified based on their size, with particles with a diameter of 2.5 µm or less (PM2.5) and PM10 (10 µm or less), also called coarse particles, and ultrafine particles (PM0.1), all of them being studied in 

relation to lung cancer [20].

 PM2.5 can penetrate deep into the respiratory system, reaching the lungs’ alveolar regions [21]. 

Inhaled fine PM deposited on the surface of the airways may either stay intact or partially dissolve but can also be cleared by mucociliary clearance and phagocytosis [22]

. PM can carry various carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), heavy metals, and organic compounds, which have been linked to cancer development, including in the lungs [23].

 Air pollution gases include nitrogen oxides (NOx: NO and NO2) and sulfur dioxide (SO2), which are produced primarily from combustion processes, such as those occurring in vehicle engines, power plants, and industrial facilities [24]. These pollutants can react with other compounds in the atmosphere to form secondary pollutants, such as nitric acid (HNO3) and ozone (O3) [25].

 Studies have shown that exposure to nitrogen oxides, particularly in combination with other pollutants, increases the risk of lung cancer [26].

 O3, a key component of photochemical smog, is another important air pollutant formed by the reaction of nitrogen oxides with volatile organic compounds (VOCs) in the presence of sunlight [27].

 Prolonged exposure to ozone has been associated with adverse respiratory effects, and recent research also indicates a potential link between ozone exposure and lung cancer development [28]. 

Volatile organic compounds are also present in air pollution and are emitted from a wide range of sources, including industrial processes, vehicle emissions, and solvents [29].

 Some VOCs, such as benzene, formaldehyde, and 1,3-butadiene, have been classified as carcinogens by the IARC [30]. 

All these pollutants may act in cells and tissues individually but also as mixtures. Therefore, air pollution includes a variety of compounds that, after long-term exposure, can contribute to an increased risk of developing lung cancer, particularly non-small cell lung cancer (NSCLC) [31].

Air Pollution and the Development of Lung Cancer: Potential Mechanisms of Damage and Relevance of EVs

Several mechanisms that could lead to lung carcinogenesis are activated by air pollutants, individually and as mixtures. 

The most studied factors contributing to lung carcinogenesis include low-grade, chronic inflammation, oxidative stress, direct mutagenesis, epigenetic changes, and mitochondrial and endothelial dysfunction, but there are many others. EVs can contribute to some of these mechanisms to carry on signals to other cells and even contribute to adapting to air pollution damage. A summary of air pollution-related damage and the role

 of EVs is shown in Fig. 1.

Fig. 1.

 The fig shores pathway of air pollutants malignant tumouurs and metastasis

Conclusions 

Addressing the impact of ambient air pollutants on lung health is highly relevant due to the adverse effects these pollutants have on respiratory symptoms,

 lung function, and the development of lung cancer [121••]. This risk is more prominent in a climate change context with an increased number of wildfires worldwide [122].

 The link between air pollutants and lung cancer is now well-established, with particulate matter, NOx, PM2.5, and volatile organic compounds being key contributors [26, 121••].

 These pollutants can carry direct carcinogens and induce systemic, long-term inflammation, and oxidative stress in the lung cells, leading to DNA damage, mutations, epigenetic changes, the release of EVs, and the promotion of tumor growth and progression [59, 123]. Inflammatory signaling pathways, sometimes modulated by EVs, facilitate a tumor-promoting microenvironment that supports the development of lung cancer [124•].

 Effective strategies and interventions to mitigate the harmful effects of air pollutants, including developing biomonitoring of these interventions, which could include EV and EV-cargo, on lung health are needed [125•]

. By addressing air pollution exposures in multiple ways (e.g., promoting clean energy sources, improving industrial practices with stricter emission standards, mandating and incentivizing stricter fuel efficiency standards for vehicles, strengthening air quality standards and regulations, reduce deforestation),

 we can protect public health and improve outcomes for individuals affected by air pollution-related lung cancer [121••, 126].

 EVs are critical components of liquid biopsy that will revolutionize medical follow-up in clinical oncology, especially in lung cancer, analyzing not only their number but their composition (miRNAs, lncRNAs, metabolites, peptides) and understanding tumor phenotypes in plasma without needing access to the tumors directly [127].

   

Tobacco Cessation in Lung cancer

 3.6. The Importance of Tobacco Cessation

Tobacco is a known cause of various types of tumors, accounting for approximately 85% of lung cancer cases and 30% of cancer mortality [84].

Optimizing smoking cessation services within an LDCT lung cancer screening program has the potential to improve the cost-effectiveness and the overall efficacy [85].

However, there is limited evidence regarding the optimal design and integration of tobacco cessation services.

A personalized intervention booklet, utilizing LDCT scan images, has been developed for delivery by trained smoking cessation practitioners. The results highlight the benefits of co-development during intervention creation and emphasize the need for further evaluating its effectiveness [86].

In a study by Park et al. [86], the impact of counseling using the 5As approach (Ask about smoking, Advise to quit, Assess readiness to quit, Assist with tobacco dependence treatment, and Arrange follow-up) on smoking cessation was evaluated. The study focused on a subset of smokers enrolled in the National Lung Screening Trial (NLST). The results showed that the “assist” and “arrange” steps of 5As counseling were associated with increased odds of quitting at 12 months.

In a study by Bade et al. [87], smoking cessation rates were compared between patients who underwent LDCT screening and those who did not. The study revealed higher smoking cessation rates among patients who attended counseling sessions in the LDCT screening group at 12 months (14.6%) and 24 months (12.9%) compared to those who did not attend counseling (12 months: 6.7%, 24 months: 7.6%, p-values from the analysis: p < 0.0001 and p = 0.002, respectively).

In order to be effective, lung cancer screening requires a multidisciplinary approach, encompassing individualized risk assessment, shared decision making, smoking cessation, structured reporting, high-quality multi-specialty cancer care, and reliable follow-up. Specialized organizations have outlined the key components and metrics that screening programs should incorporate. Ongoing research focuses on long-term outcomes, the refinement of screening criteria, and the use of biomarkers for early cancer detection [88].

A quasi-experimental study by Luh et al. examined a screening program emphasizing primary prevention by encouraging smoking cessation [89]. The study found that patients who received counseling from physicians and nurses showed greater odds of advancing in terms of readiness to quit compared to a control group (OR 2.27, 95% CI 1.07–4.84), while patients who received a smoking cessation leaflet had no significant difference (OR 0.99, 95% CI 0.44–2.25). [90].

Zeliadt et al. conducted a pilot feasibility trial to evaluate the impact of proactive outreach telephone counseling on behavioral cessation support and quit rates [90]. The study showed that patients who received the intervention had higher rates of using behavioral cessation support programs than the control group (44% vs. 11%, RR 4.1, 95% CI 1.7–9.9).

Lung cancer screening could prompt current smokers to reflect on their health and might present an opportunity to engage them in discussions about smoking cessation.

Ref

Healthcare (Basel). 2023 Jul 21;11(14):2085. doi: 10.3390/healthcare11142085

Systematic Review of Lung Cancer Screening: Advancements and Strategies for Implementation

Daniela Amicizia 1,2, Maria Francesca Piazza 1,*, Francesca Marchini 1, Matteo Astengo 1, Federico Grammatico 1,2, Alberto Battaglini 1, Irene Schenone 1, Camilla Sticchi 1, Rosa Lavieri 1, Bruno Di Silverio 1, Giovanni Battista Andreoli 1, Filippo Ansaldi 1,2

Editor: Clara Benna

Lung Cancer conclusions

 Conclusions

Risk factors for lung cancer have been mostly understood and well characterized. Primary prevention of this disease therefore 

seems to be easy to implement by eliminating environmental hazards and smoking.

 Despite this, lung cancer remains the leading cause of death among malignant cancers in all highly developed countries. The causes of this

 phenomenon should be sought in the growing problem of environmental pollution,

 but above all in the difficulty of eliminating the addiction to smoking. In the prevention of lung cancer, the basic factor is not smoking. 

Tobacco smoke is the most common cause of lung cancer. It is worth noting that electronic cigarettes are also not recommended in the context of prevention. The lack of proper education means that young people continue to reach for nicotine-containing products, first e-cigarettes and then traditional cigarettes. However, nicotine addiction is extremely strong in many people, and eliminating the addiction using traditional methods (psychotherapy, nicotine replacement therapy, pharmacotherapy) turns out to be impossible. In such cases, reducing the health risk associated with smoking cigarettes can be achieved by replacing them with smokeless products containing nicotine. Many scientific studies have shown that aerosols from e-cigarettes and tobacco heating devices contain over 90% less carcinogenic substances than cigarette smoke [145].

However, it should be remembered that while the composition of the aerosol is known in tobacco heating devices, in the case of e-liquids, it can be modified by the owners of e-cigarettes or the companies producing them (this has been the cause of many cases of acute lung injury in people using e-liquids containing THC and vitamin E acetate). Therefore, in many countries (USA, the Netherlands, Belgium, Germany), HnB devices have been defined as products with a reduced health risk compared to traditional cigarettes, and international experts issue cautious recommendations on the possibility of reducing the health risk in cigarette smokers by replacing them with tobacco heating products [146].

It has been proven that proper nutrition, with particular emphasis on vegetables and fruits, as well as regular physical activity have a positive effect on reducing the risk of lung cancer [147].

Preventive programs are also being carried out for people who are potentially at risk of developing this type of cancer. The screening test involves performing a low-dose computed tomography scan to detect lung cancer at an early stage [148].

To sum up, the vast majority of lung cancer

 cases are the result of inhalation of substances that promote their formation, e.g., tobacco smoke, car exhaust fumes and smoke from burning coal. Proper prevention of lung cancer and reduction

 in exposure to carcinogens increase the chance of staying healthy.

Ref

Int J Mol Sci. 2025 Feb 26;26(5):2049. doi: 10.3390/ijms26052049

Lung Cancer—Epidemiology, Pathogenesis, Treatment and

 Molecular Aspect of literature 

 Beata Smolarz 1,*, Honorata Ł

ukasiewicz 2, Dariusz Samulak 3,4, Ewa Piekarska 5, Radosław Kołaciński 5, Hanna Romanowicz 1

Editor: Verena Trett

Lung cancer Risk Factors

 8. Risk Factors

The most important risk factor for lung cancer is smoking, primarily active smoking, but there is objective 

evidence that passive smoking is also important. Smoking is the cause of 80–90% of lung cancer cases, and the lifetime risk of developing lung cancer among male smokers is about 17%, among smoking women is about 12%, and among non-smokers is about 1.5% [36,78].

The literature emphasizes the higher risk of lung cancer in people with long-term exposure to compounds such as radon, asbestos, polycyclic aromatic hydrocarbons, arsenic, beryllium, cadmium, silicone, vinyl chloride, nickel and chromium compounds and diesel engine exhaust [79,80].

 The compounds mentioned above are characterized by a high genotoxic potential, which contributes to the formation of numerous oxidative and nitrative damages.

 In addition, multidirectional activation of signal transduction pathways is observed, as well as the production of the “cross-talk” phenomenon, which leads to an increase in uncontrolled cellular proliferation [81]. 

Exposure of the lung area to ionizing radiation applied for other cancers (e.g., early Hodgkin lymphoma or breast cancer) as well as environmental pollution also increases the risk of lung cancer [36].

 The occurrence of lung cancer in first-degree relatives is associated with a higher risk of developing the disease than in the general population [82,83].

Lung cancer is most often caused by smoking, but in some patients, it is associated with genetic predisposition, according to a study published by the American Society of Clinical Oncology (ASCO).

 American specialists have shown that the same predisposition can cause other types of cancer in patients with lung cancer, such as pancreatic cancer, ovarian cancer in women and prostate cancer in men. 

They warn that the patient’s closest relatives may also be at greater risk of cancer. 

Experts from the American Society of Clinical Oncology point out that most lung cancers can be associated with cigarette smoking, as well as other environmental factors, such as exposure to asbestos, but in the case of thousands of patients, the development of this disease is driven by inherited genetic factors.

 Until now, it seemed that adverse genetic changes conducive to lung cancer could be caused by adverse environmental factors, as well as improper lifestyle, including, above all, smoking. However, some people have inherited genetic changes that predispose them more to this cancer. 

Research by American specialists shows that the detection of inherited genetic changes (pathogenic germline variants—PGV) is therefore of great importance in predicting the risk of lung cancer.

 It has been established that it occurs in a fairly large group, 15% of patients with lung cancer. This is also important information for the closest relatives of these patients. 

Early detection of genetic predisposition allows one to reduce the risk of this disease, as well as detect it early, when even more effective treatment is possible [84]. 

The study included 7788 patients with lung cancer, among whom 1161 patients were found to have inherited genetic changes in 81 known cancer mutations so far. 

Approximately 95.1% of patients with these lesions could be treated with available therapies or could be covered by early detection of the disease ,(84)

Fig 6 Risk factors

Smoking

 Smoking is the cause of 90% of lung cancer cases in men and 80% in women. Smokers have a 30 times higher risk of death from lung cancer than non-smokers. Cigarette smoke hides over 7000 chemical compounds, including over 70 compounds considered carcinogenic.

Secondhand smoke is also associated with a higher risk of lung cancer compared to people who are not exposed to tobacco smoke. It is estimated that about 20–50% of “non-smokers” who suffer from lung cancer are passive smokers [85].

Alcohol

alcohol Studies indicate that people who abused alcohol were more likely to develop lung cancer.

 Researchers do not provide exact data but estimate that it may be related to another factor: smoking. Studies show that people are more likely to reach for cigarettes when they drink.

 Researchers at the University of Liverpool studied 125,249 British drinkers and 47,967 Americans. As many as six genes have been identified that, in their opinion, are associated with excessive alcohol consumption and, consequently, with lung cancer [86].

Genetic predisposition

genetic predisposition The role of genetic factors is still quite poorly understood. The high incidence of lung cancer 

in some families is associated with a genetically determined tendency to overactivate carcinogenic compounds contained in tobacco smoke or to remove these compounds from the body too slowly. A tendency to slowly repair DNA damage in respiratory epithelial cells after the action of carcinogens is also inherited. To sum up, it can be stated that the hereditary condition is primarily a special susceptibility to the carcinogenic effects of tobacco. This inheritance is the result of the presence of polymorphisms (population variants) in many genes, and there are currently no reliable genetic tests to determine the high risk of developing lung cancer.

Research by American specialists shows that the detection of inherited genetic changes (pathogenic germline variants—PGV) is of great importance in predicting the risk of lung cancer. It has been established that it occurs in a fairly large group, i.e., 15% of patients with lung cancer [84].

Occupational factors

occupational factors Exposure to many occupational factors has consequences in the form of the development of lung diseases, including lung cancer. The most important occupational carcinogens include asbestos, silica, heavy metals and polycyclic aromatic hydrocarbons [87]. All forms of asbestos (chrysotile and amphiboles, including crocidolite, amosite and tremolite) are carcinogenic, although the potency of chrysotile is less than that of other types, likely due to its more effective removal from the lungs. In many underdeveloped countries, occupational exposure to asbestos remains widespread [87,88].

Elevated risk of lung cancer has been reported in several industries and occupations associated with exposure to polycyclic aromatic hydrocarbons, such as aluminum production, coal gasification, coke production, iron and steel foundries, tar distillation, roofing and chimney cleaning. It has also been suggested that people employed in several other industries have increased risk of lung cancer, including shale oil mining, wood impregnation, roofing and carbon electrode manufacturing [88].

Environmental  factors 

environmental factors Air pollution data show that lung cancer incidence increases by 30–50% in areas with high levels of ambient air pollution compared to areas with lower levels [89,90].

Many studies carried out so far clearly show that the risk of developing lung cancer is much higher in highly urbanized, industrialized regions with a developed transport network, in particular based on the use of internal combustion engines [37].

age The risk of developing lung cancer also increases with age. 

The majority of lung cancers occur after the age of 50

 (96% of cases in men and 95% of cases in women), with about 50% of cases in both sexes occurring in the population over 65 years of age. The risk of developing lung cancer peaks in men in the eighth decade of life and in women at the turn of the sixth and seventh decades of life [25].

Ref

Int J Mol Sci. 2025 Feb 26;26(5):2049. doi: 10.3390/ijms26052049

Lung Cancer—Epidemiology, Pathogenesis, Treatment and

 Molecular Aspect of literature 

 Beata Smolarz 1,*, Honorata Ł

ukasiewicz 2, Dariusz Samulak 3,4, Ewa Piekarska 5, Radosław Kołaciński 5, Hanna Romanowicz 1

Editor: Verena Trett