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Updated: Aug 11, 2026
Detection of Targetable Alterations in Non-small Cell Lung Cancer using Next-generation Sequencing
Published on: October 10, 2025
Other compounds and targets in non-small cell lung cancer
Victoria Villaflor1, Philip Bonomi
1Division of Hematology & Medical Oncology, Rush University Medical Center, Chicago, IL 60612, USA. Victoria_Villaflor@rsh.net
Abstract:
It has become increasingly apparent in recent years that a therapeutic plateau has been reached for patients with advanced stage non-small cell lung cancer (NSCLC) treated with conventional cytotoxic agents. As a result, investigators have directed their efforts toward the development of treatments encompassing novel targeted agents. Apoptosis is one of many cellular pathways currently under investigation as a therapeutic target for the treatment of NSCLC. Anti-inflammatory agents, including cyclooxygenase inhibitors, have been shown to inhibit apoptosis and appear promising based on preclinical studies. However, several phase II studies indicate that this therapeutic strategy is unlikely to be successful. In contrast, the proteosome inhibitor bortezomib has shown promise in preliminary studies, and further efforts to elucidate the role this agent may play in the treatment of NSCLC are ongoing. Agonists of the tumor necrosis factor-related, apoptosis-inducing ligand have also entered into early clinical studies in patients with NSCLC. Further studies will be needed to fully clarify how agents targeting the apoptotic pathway can be used in the treatment of NSCLC, but the results of current clinical trials suggest that certain agents may be active.
Insights
Conventional treatments for advanced non-small cell lung cancer (NSCLC) show limited efficacy. Novel targeted therapies, particularly those modulating apoptosis, are under investigation, with some agents showing promise.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Advanced non-small cell lung cancer (NSCLC) treatment has plateaued with conventional cytotoxic agents.
- Novel targeted therapies are being explored to overcome treatment resistance.
- Apoptosis, a key cellular pathway, is a focus for developing new NSCLC treatments.
Purpose of the Study:
- To review emerging targeted agents and their role in modulating apoptosis for NSCLC treatment.
- To evaluate the potential of novel therapeutic strategies beyond traditional chemotherapy.
Main Methods:
- Review of preclinical studies and early-phase clinical trials.
- Investigation of agents targeting the apoptosis pathway, including anti-inflammatory drugs, proteasome inhibitors, and TNF-related apoptosis-inducing ligands.
Main Results:
- Anti-inflammatory agents (cyclooxygenase inhibitors) showed preclinical promise but failed in Phase II studies for NSCLC.
- The proteasome inhibitor bortezomib demonstrates preliminary promise in NSCLC treatment.
- Agonists of tumor necrosis factor-related, apoptosis-inducing ligand are in early clinical investigation for NSCLC.
Conclusions:
- Targeting the apoptosis pathway represents a promising avenue for advanced NSCLC treatment.
- While some agents like bortezomib show potential, further research is needed to clarify their role.
- Current clinical trials suggest that specific apoptosis-targeting agents may be active in NSCLC therapy.
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