International Journal of Inflammation, Cancer and Integrative Therapy
Open Access

Lung cancer; Cancer stem cells; Molecular features; Therapeutic targets; Tumorigenesis; Metastasis; Therapy resistance; Tumor microenvironment; Self-renewal; Treatment susceptibility; Patient outcomes

Introduction

Lung cancer remains a formidable global health concern, responsible for a substantial portion of cancer-related deaths. The intricacies of this disease, characterized by its diverse subtypes and limited treatment options, have prompted a deeper investigation into the underlying mechanisms driving its progression and resistance to therapy [4]. Recent advancements in cancer research have illuminated the significance of a distinct subset of cells within lung tumors known as lung cancer stem cells (CSCs). These cells, endowed with unique properties reminiscent of stem cells, have emerged as key orchestrators of tumorigenesis, metastasis, therapeutic resistance, and disease recurrence [4].

Less than 15% of patients with lung cancer survive five years after diagnosis because the disease is very diverse and resistant to treatment drugs. Even with tremendous improvements in our understanding of genetic mutations and signalling pathway aberrations, it has been challenging to pinpoint the causes of lung cancer heterogeneity and medication resistance. Recent years have seen a substantial increase in interest in the cancer stem cell model as a possible explanation for the heterogeneity, drug resistance, dormancy, recurrence, and metastasis of diverse tumours [6]. Cancer stem cells have also been studied in lung tumours, though comparatively little. This overview provides an overview of our current knowledge of lung cancer stem cells, including their molecular characteristics and the signalling networks that support them. This evaluation also covers the prospective.

The objective of this article is to provide a comprehensive overview of the molecular features of lung CSCs and the potential therapeutic targets that hold promise for improving patient outcomes. By delving into the intricacies of lung CSC biology, including their identification [7], regulatory pathways, and interactions within the tumor microenvironment, we aim to shed light on novel strategies for combating the challenges posed by lung cancer.

Understanding lung cancer stem cells

Lung CSCs are a subpopulation of cells within the tumor that share characteristics with stem cells, including self-renewal and differentiation capabilities. These cells are implicated in the initiation and progression of lung cancer, driving the heterogeneous nature of the disease. Through their distinct molecular features, lung CSCs play a significant role in shaping the tumor's behavior, including its potential to metastasize and resist therapeutic interventions [8].

Molecular features and regulatory pathways

This article extensively explores the molecular signatures that define lung CSCs. These features include the expression of specific markers, activation of signaling pathways, and genetic alterations that contribute to their stem-like properties. Regulatory pathways such as Notch, Wnt, and Hedgehog are discussed in the context of their role in maintaining lung CSC self-renewal and survival, providing insights into potential targets for intervention [v].

Interactions within the tumor microenvironment

Lung CSCs do not operate in isolation; they exist within the dynamic milieu of the tumor microenvironment. Interactions with immune cells, stromal cells, and extracellular matrix components influence their behavior and contribute to disease progression. Understanding these interactions is pivotal for designing strategies that disrupt the supportive microenvironment and target lung CSCs effectively.

Molecular complexity of lung CSCs

Lung CSCs, characterized by their stem-like properties, contribute to tumor heterogeneity, metastasis, and therapy resistance. The diverse molecular features that define these cells underscore their capacity for self-renewal and tumor initiation. The discussion highlights the multifaceted nature of lung CSCs, emphasizing the importance of deciphering their molecular intricacies for therapeutic advancement [10].

Tumor microenvironment: influences on CSCs behaviour

The intricate interplay between lung CSCs and the tumor microenvironment significantly influences disease progression and therapeutic responses. The discussion delves into the reciprocal interactions between CSCs and various cellular components of the microenvironment. Strategies aimed at disrupting these interactions hold the potential to alter the supportive niche and enhance treatment efficacy.

Challenges and future directions

While the potential therapeutic targeting of lung CSCs offers promising opportunities, challenges persist. The heterogeneity of CSC populations within and between tumors, as well as the potential for normal stem cell disruption, necessitates careful consideration [11]. The discussion highlights the need for innovative technologies and approaches to characterize and target CSC subsets effectively.

Clinical translation and therapeutic impact

Translating the insights gained from understanding lung CSCs into clinical applications remains a critical objective. The discussion emphasizes the potential therapeutic impact of CSC-targeted strategies, including the ability to mitigate therapy resistance and improve patient outcomes. The integration of CSC-targeting approaches with existing therapies offers a comprehensive approach to address the complexities of lung cancer treatment.

Personalized medicine and future prospects

The era of personalized medicine holds great promise for the management of lung cancer. By tailoring treatments to the unique molecular profiles of individual tumors, including their CSC populations, researchers can optimize therapeutic strategies for maximum efficacy. The discussion underscores the potential of personalized approaches to redefine the landscape of lung cancer treatment [12].

Conclusion

In unraveling the molecular features of lung CSCs and their potential as therapeutic targets, we embark on a journey toward more effective lung cancer treatments. The intricate interplay between lung CSCs, their molecular characteristics, and the tumor microenvironment provides valuable insights that may pave the way for innovative therapeutic interventions. As we delve into the complexities of lung cancer stem cells, we aim to advance our understanding and ultimately improve patient outcomes in the challenging landscape of lung cancer.

Acknowledgement

None

Conflict of Interest

None

1. Winter JM, Cameron JL, Campbell KA (2006) 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg 10: 1199-1210.

Indexed at, Google Scholar, Crossref

2. Tempero MA, Malafa MP, Al-Hawary M (2021) Pancreatic adenocarcinoma, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 19: 439-457.

Indexed at, Google Scholar, Crossref

3. Muller SA, Hartel M, Mehrabi A (2009) Vascular resection in pancreatic cancer surgery: survival determinants. J Gastrointest Surg 13: 784-792.

Indexed at, Google Scholar, Crossref

4. Tseng JF, Raut CP, Lee JE (2004) Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 8: 935-949.

Indexed at, Google Scholar, Crossref

5. Marjanovic ND, Weinberg RA, Chaffer CL (2013) Cell plasticity and heterogeneity in cancer. Clin Chem 59: 168-179.

Indexed at, Google Scholar, Crossref

6. Vermeulen L, Todaro M, de Sousa Mello F, Sprick MR, Kemper K (2008) Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity. Proc Natl Acad Sci USA 105: 13427-13432.

Indexed at, Google Scholar, Crossref

7. Liu X, Johnson S, Liu S, Kanojia D, Yue W (2013) Nonlinear growth kinetics of breast cancer stem cells: implications for cancer stem cell targeted therapy. Sci Rep 3: 2473.

Indexed at, Google Scholar, Crossref

8. Luo Y, Yang Z, Su L, Shan J, Xu H (2016) NonCSCs nourish CSCs through interleukin-17E-mediated activation of NF-kappaB and JAK/STAT3 signaling in human hepatocellular carcinoma. Cancer Lett 375: 390-399.

Indexed at, Google Scholar, Crossref

9. Kickhoefer VA, Rajavel KS, Scheffer GL, Dalton WS, Scheper RJ, et al. (1998) Vaults are up-regulated in multidrug-resistant cancer cell lines. J Biol Chem 273: 8971-8974.

Indexed at, Google Scholar, Crossref

10. Lotsch D, Steiner E, Holzmann K, Kreinecher SS, Pirker C, et al. (2013) Major vault protein supports glioblastoma survival and migration by upregulating the EGFR/PI3K signalling axis. Oncotarget 4: 1904-1918.

Indexed at, Google Scholar, Crossref

11. Liu Z, Zhang W, Phillips JB, Arora R, McClellan S, et al. (2019) Immunoregulatory protein B7-H3 regulates cancer stem cell enrichment and drug resistance through MVP-mediated MEK activation. Oncogene 1: 88-102.

Indexed at, Google Scholar, Crossref

12. Kim E, Lee S, Mian MF, Yun SU, Song M, et al. (2006) Crosstalk between Src and major vault protein in epidermal growth factor-dependent cell signalling. FEBS J 273: 793-804.

Indexed at, Google Scholar, Crossref