Modern therapies of nonsmall cell lung cancer

Abstract

Lung cancer (LC), particularly nonsmall cell lung cancer (NSCLC), is one of the most prevalent types of neoplasia worldwide, regardless of gender, with the highest mortality rates in oncology. Over the years, treatment for NSCLC has evolved from conventional surgery, chemotherapy, and radiotherapy to more tailored and minimally invasive approaches. The use of personalised therapies has increased the expected efficacy of treatment while simultaneously reducing the frequency of severe adverse effects (AEs). In this review, we discuss established modern approaches, including immunotherapy and targeted therapy, as well as experimental molecular methods like clustered regularly interspaced short palindromic repeat (CRISPR) and nanoparticles. These emerging methods offer promising outcomes and shorten the recovery time for various patients. Recent advances in the diagnostic field, including imaging and genetic profiling, have enabled the implementation of these methods. The versatility of these modern therapies allows for multiple treatment options, such as single-agent use, combination with existing conventional treatments, or incorporation into new regimens. As a result, patients can survive even in the advanced stages of NSCLC, leading to increased survival indicators such as overall survival (OS) and progression-free survival (PFS).

Keywords: CRISPR; Immunotherapy; Lung cancer; NSCLC; Nanoparticles; Targeted therapy.

Fig. 1

Interaction between immune checkpoint inhibitor ligands, their corresponding receptors (A, C), and most commonly used immunotherapeutic drugs (B, D). PD-1, programmed death receptor; PD-L1, programmed death ligand 1; CTLA4, cytotoxic T-lymphocyte associated protein 4; B7, B7 compound family molecules; CD28, cluster differentiation protein 28; immunoterapeutic drugs are portrayed as symbols of antibodies, visualising their immune checkpoint blocking capabilities

Fig. 2

Interaction of VEGF and VEGFR with immunotherapeutic drugs. VEGF, vascular endothelial growth factor; VEGFR, vascular endothelial growth factor receptor; immunoterapeutic drugs are portrayed as symbols of antibodies, visualising their blocking capabilities. Red lines represent blood vessels; grey arrows visualize expanding tumour mass

Fig. 3

The simplified impact of selected drugs on the inhibition of the EGFR pathway. Medication is applied when proper mutations are detected in the genes that encode the pathway proteins. EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; ROS1, proto-oncogene C-Ros 1; ALK, anaplastic lymphoma kinase; RAS, KRAS proto-oncogene; RAF, B-Raf proto-oncogene; MEK, mitogen-activated protein kinase kinase 1; ERK, mitogen-activated protein kinase kinase 3

Fig. 4

Potential application of Crisp-Cas system in the treatment of NSCLC. Increasing the possibilities of drugs used in the cancer treatment (A); caveolin-1 is a structural protein in caveolae. Its overexpression in cancer cells leads to the upregulation of anti-apoptotic genes. Thus, the knockout of the caveolin-1 (CAV-1) gene by CRISPR-Cas9-mediated gene editing leads to a decrease in its synthesis and a decrease in its number in caveolae. This process causes the downregulation of anti-apoptotic gene transcription in targeted NSCLC cells which reverts them to be sensitive to radiation (B)