Precision Reprogramming of Lung Cancer Biomarkers via CRISPR/Cas9: A Paradigm Shift in Personalized Immunotherapy

• Mohd Rizwan Jameel

  Centre for Interdisciplinary Research in Basic Science, Jamia Milia Islamia, New Delhi – 110025, India

• Amar Arora

  Banasthali Vidyapith, Banasthali -304022, Rajasthan, India

• Prem Shankar Mishra

  Faculty of Pharmacy, Vidya University, Meerut 250002, Uttar Pradesh, India

• Hina Jameel

  Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh-202001, India

• Mudassir Jan Makhdoomi

  All India Institute of Medical Sciences, Ansari Nagar, New Delhi, 110029, India

• Abid Ali Sheikh

  National Institute of Biologicals, Sector 62, Noida -201309, Uttar Pradesh, India

Lung cancer persists as the leading cause of cancer-related mortality globally, largely due to late detection, genomic complexity, and limited durability of existing therapeutic interventions. The integration of CRISPR/Cas9 gene-editing systems with biomarker-driven therapeutic strategies represents a transformative advance in precision oncology. Biomarkers—including genetic mutations, epigenetic alterations, protein signatures, and circulating analytes—enable early detection, patient stratification, and dynamic monitoring of therapeutic response. CRISPR/Cas9 offers a unique opportunity to directly reprogram these biomarkers or the pathways regulating them, enhancing tumor immunogenicity, reversing immune evasion mechanisms, and strengthening anti-tumor immune responses. Preclinical models demonstrate that CRISPR-mediated biomarker editing can restore antigen presentation, augment T-cell cytotoxicity, sensitize resistant tumors to immunotherapy, and improve tumor regression. Early clinical trials further validate the feasibility and safety of CRISPR-engineered immune cells in patients.

However, major challenges persist, including off-target editing, inefficient delivery to solid tumors, tumor microenvironment–mediated suppression, and ethical considerations linked to genome manipulation. Rapid advancements in editing fidelity, lipid nanoparticle systems, viral vectors, engineered vesicles, high-throughput biomarker discovery, and artificial intelligence–assisted CRISPR design are expected to accelerate clinical translation. This review synthesizes the current landscape, mechanistic underpinnings, emerging applications, and future directions of CRISPR/Cas9-enabled biomarker engineering for lung cancer immunotherapy, positioning this technology as a cornerstone of next-generation personalized oncology.

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