Mini Review •International Open Medical Journal. 1(1):e202504

Emerging Challenges in the Treatment of Lung Cancer: Insights from Recent Advances

Authors

John Smith¹, James Williams¹

Affiliations

1 Department of Biomedical Engineering, Duke University, Durham, NC, USA

Abstract:

Lung cancer remains one of the leading causes of cancer-related mortality worldwide, despite significant advancements in therapeutic strategies. This review examines the latest challenges in the treatment of lung cancer, focusing on therapeutic resistance, the limitations of current treatment modalities, and emerging strategies to overcome these hurdles. Immunotherapy, targeted therapy, and novel approaches such as personalized medicine, nanoparticle systems, and the integration of artificial intelligence in diagnostics are discussed in detail. Special emphasis is placed on overcoming treatment resistance, managing side effects, and improving patient outcomes. Recent advances in screening techniques and the role of multidisciplinary approaches in lung cancer management are also explored. This review aims to provide a comprehensive understanding of the current state of lung cancer treatment and the challenges that still need to be addressed to enhance clinical outcomes.

Keywords:

Lung cancer, treatment challenges, therapeutic resistance, immunotherapy, targeted therapy, personalized medicine, nanoparticle systems, screening, artificial intelligence

 Introduction

Lung cancer is the most common cause of cancer-related death worldwide. Despite significant progress in research and the development of targeted therapies and immunotherapies, the overall survival rate for lung cancer remains low. The management of lung cancer has evolved significantly over the past few decades, with therapies tailored to specific genetic mutations, such as epidermal growth factor receptor (EGFR) mutations, anaplastic lymphoma kinase (ALK) rearrangements, and programmed death-ligand 1 (PD-L1) overexpression. However, numerous challenges still exist, particularly with the development of therapeutic resistance, side effects, and the late-stage diagnosis of many lung cancer cases. This review highlights the current treatment challenges in lung cancer, examining both established and emerging therapies aimed at improving patient outcomes.

Therapeutic Resistance in Lung Cancer

Therapeutic resistance remains one of the most significant barriers to effective lung cancer treatment. Resistance can occur through multiple mechanisms, including genetic mutations, epigenetic alterations, and tumor microenvironment changes. Even with the development of targeted therapies and immunotherapies, many patients eventually develop resistance, leading to disease progression.

• Targeted Therapy Resistance: Although EGFR inhibitors such as gefitinib and osimertinib have demonstrated effectiveness in patients with EGFR-mutated non-small-cell lung cancer (NSCLC), resistance develops in a significant proportion of cases due to secondary mutations (e.g., T790M mutation) (Ashrafi et al., 2022; Guo et al., 2022).
• Immunotherapy Resistance: Immune checkpoint inhibitors (ICIs), such as pembrolizumab and nivolumab, have revolutionized the treatment of NSCLC. However, resistance to ICIs remains a significant issue, with around 70% of patients failing to respond or developing resistance after initial success (Mamdani et al., 2022; Li et al., 2022).
• Combination Therapies: Combining targeted therapies with immunotherapies, chemotherapy, or radiation has shown promise in overcoming resistance, but challenges remain in optimizing these combinations for better efficacy and reduced toxicity (Singh et al., 2022; Remon et al., 2023).

 Emerging Strategies for Overcoming Resistance

In the face of therapeutic resistance, novel strategies are being explored to improve the efficacy of existing treatments and overcome resistance mechanisms.

• Next-Generation Targeted Therapies: The development of next-generation inhibitors targeting resistant mutations, such as those targeting MET amplification or KRAS mutations, is underway. These therapies aim to address the genetic heterogeneity of lung cancer and prevent or overcome resistance (Guo et al., 2022; Sadik et al., 2022).
• Immunotherapy Combinations: Combining ICIs with targeted therapies or chemotherapy has been shown to enhance immune response and overcome immune resistance. Ongoing trials are evaluating the efficacy of such combinations in both first-line and second-line treatments (Meyer et al., 2023; Hendriks et al., 2024).
• Nanoparticle Drug Delivery Systems: Nanotechnology-based drug delivery systems offer targeted treatment to tumor sites, potentially reducing off-target effects and overcoming drug resistance. Nanoparticles can also be used to deliver gene therapies or immunotherapies directly to the tumor microenvironment (Singh et al., 2022).
• Artificial Intelligence in Diagnostics and Treatment Planning: AI is being utilized to predict resistance patterns, personalize treatment plans, and enhance early detection through advanced imaging and molecular profiling (Li et al., 2022; Guo et al., 2022).

Challenges in Current Treatment Modalities

Despite the promising advances in targeted therapies and immunotherapy, there are significant limitations to current treatment modalities, including the following:

• Adverse Side Effects: While targeted therapies and immunotherapies have improved survival, they are often associated with significant side effects, such as immune-related adverse events or drug resistance-associated toxicities (Mamdani et al., 2022; Ashrafi et al., 2022). Balancing efficacy and side effects is crucial for improving patient quality of life.
• Late-Stage Diagnosis: Most lung cancer patients are diagnosed at an advanced stage, when the disease is no longer amenable to curative therapies. Early detection remains a challenge, and current screening methods (e.g., low-dose CT) have limitations in terms of sensitivity and specificity (Li et al., 2022; Sadik et al., 2022).
• Cost and Accessibility: The high cost of novel therapies, including immunotherapy and personalized treatments, poses significant challenges for their widespread adoption, particularly in low- and middle-income countries (Meyer et al., 2023; Hendriks et al., 2024).

 The Role of Multidisciplinary Approaches

A multidisciplinary approach to lung cancer treatment involves the collaboration of various specialists, including oncologists, radiologists, pathologists, and surgeons, to optimize patient outcomes. This approach can help in personalized treatment planning, reducing unnecessary treatments, and providing a comprehensive treatment strategy for each patient.

• Surgical Resection and Adjuvant Therapy: For early-stage lung cancer, surgery remains the gold standard. However, for resectable NSCLC, the integration of chemotherapy or immunotherapy in the adjuvant setting has shown promising results (Mamdani et al., 2022).
• Palliative Care: For patients with advanced lung cancer, the integration of palliative care is essential to manage symptoms and improve quality of life. Personalized symptom management and timely interventions are key to improving patient satisfaction and survival (Temel et al., 2022; Sadik et al., 2022).

Conclusion

Lung cancer treatment continues to face several challenges, including therapeutic resistance, adverse side effects, late-stage diagnosis, and high treatment costs. However, the ongoing development of next-generation therapies, combination treatment strategies, and the integration of AI in diagnostics offer hope for overcoming these challenges. A multidisciplinary approach is crucial to optimizing treatment outcomes and improving the quality of life for lung cancer patients. Continued research is needed to explore innovative solutions that can effectively address these challenges and provide more personalized treatment options.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

References

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10. Remon, J., Mountzios, G., Hendriks, L. E. L., et al. (2023). Emerging strategies for the treatment of small cell lung cancer: A review. JAMA Oncology. Link

• Publication Dates
•  Publication in this collection
• • 07 July 2025
  •  Date of issue
    2025
  • History
  • Received 16 March2025
  •  Accepted 12 June 2025