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Published on: February 27, 2026
Second-line therapy for non-small-cell lung cancer
Belisario A Arango1, Aurelio B Castrellon, Edgardo S Santos
1Division of Hematology and Oncology, University of Miami Miller School of Medicine and Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA.
Abstract:
Carcinogenesis is a complex pathological process induced by abnormalities in the genome, cell-cycle dysregulation, loss of the programmed cell death process, and upregulation of oncogenic pathways associated with proliferation, migration, and survival, among others. Despite recent advances in molecular and tumor biology in non-small-cell lung cancer (NSCLC) and the introduction of several targeted agents, the disease continues to have a dismal survival. Nonetheless, the future looks promising; conventional cytotoxic chemotherapy regimens in combination with targeted agents have shown better response rates and survival than those seen in the past. These targeted agents have the advantage of blocking or inhibiting specific pathways necessary for tumor growth, proliferation, and metastases, without significantly affecting quality of life by having an acceptable toxicity profile. Thus, these novel agents harbor a hope in the treatment of NSCLC and many other malignant diseases when they can be used either in combination with other chemotherapy drugs in several lines of treatment or as a single agent in maintenance therapy until progression of disease, or even more attractively, in combination with other targeted agents themselves. In this review, we discuss second-line treatments for patients who have NSCLC, including targeted agents and their development in this specific setting as part of our armamentarium in lung cancer.
Insights
Targeted agents offer hope for non-small-cell lung cancer (NSCLC) treatment, improving survival rates when combined with chemotherapy. This review focuses on second-line targeted therapies for NSCLC patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Carcinogenesis involves genomic instability, cell-cycle disruption, and aberrant signaling pathways promoting cancer growth.
- Non-small-cell lung cancer (NSCLC) treatment remains challenging despite advances, with historically poor survival rates.
- Targeted agents represent a significant advancement, offering specific pathway inhibition with improved tolerability.
Purpose of the Study:
- To review the current landscape of second-line treatments for non-small-cell lung cancer (NSCLC).
- To discuss the development and role of targeted agents in the second-line setting for NSCLC.
- To highlight the potential of targeted therapies in combination strategies for advanced lung cancer.
Main Methods:
- Literature review of studies on targeted agents in NSCLC.
- Analysis of clinical trial data for second-line NSCLC treatments.
- Synthesis of information on efficacy, safety, and development of targeted therapies.
Main Results:
- Combination regimens of chemotherapy and targeted agents show improved response rates and survival in NSCLC.
- Targeted agents demonstrate efficacy by inhibiting specific oncogenic pathways crucial for tumor progression.
- Novel targeted agents offer a favorable toxicity profile compared to traditional chemotherapy.
Conclusions:
- Targeted agents are a promising addition to the NSCLC treatment armamentarium, particularly in the second-line setting.
- Combination therapies involving targeted agents hold significant potential for improving patient outcomes in NSCLC.
- Further development and strategic application of targeted therapies are crucial for advancing lung cancer care.
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