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Targeted molecules in small cell lung cancer
Nevin Murray1, Ravi Salgia, Frank V Fossella
1British Columbia Cancer Agency, Vancouver.
Abstract:
Because small cell lung cancer is decreasing in frequency in North America, the tempo of clinical trials in general and investigation of molecular-targeted therapy is less active than for non-small cell lung cancer. Nevertheless, progress in the understanding of the molecular pathogenesis of small cell lung cancer has been substantial. Potentially relevant molecular targets have been identified and drugs have been developed to exploit them. This article discusses the common expression of c-Kit receptor tyrosine kinases in small cell lung cancer and its potential to serve as an effective target for small-molecule inhibitors such as imatinib mesylate. Another innovation described is the development of an immunoconjugate (BB-10901) that links an antibody targeting the CD56 antigen of the neural cell adhesion molecule family with a potent maytansinoid cytotoxic component. These novel strategies are currently in clinical trials and potentially will allow additional therapeutic options for patients resistant to conventional strategies. Should these proof-of-concept studies show promise, integration of these agents with conventional modalities in previously untreated patients will follow.
Insights
Novel targeted therapies, including c-Kit inhibitors and CD56-targeted immunoconjugates, show promise for small cell lung cancer. These agents offer new options for patients resistant to traditional treatments.
Area of Science:
- Oncology
- Molecular Biology
- Drug Development
Background:
- Small cell lung cancer (SCLC) research lags behind non-small cell lung cancer (NSCLC) due to decreasing incidence in North America.
- Significant advancements in understanding SCLC molecular pathogenesis have identified potential therapeutic targets.
- Conventional treatments for SCLC often face resistance, necessitating novel therapeutic strategies.
Purpose of the Study:
- To explore novel molecular-targeted therapies for small cell lung cancer.
- To discuss the potential of c-Kit receptor tyrosine kinases as a therapeutic target.
- To introduce an innovative immunoconjugate targeting the CD56 antigen.
Main Methods:
- Review of molecular targets in SCLC pathogenesis.
- Discussion of small-molecule inhibitors targeting c-Kit, such as imatinib mesylate.
- Description of an antibody-drug conjugate (BB-10901) linking anti-CD56 antibody with a cytotoxic agent.
Main Results:
- c-Kit receptor tyrosine kinases are commonly expressed in SCLC, making them a viable target for inhibitors.
- An immunoconjugate (BB-10901) has been developed, targeting CD56 on SCLC cells.
- These novel agents are currently undergoing clinical trials for SCLC treatment.
Conclusions:
- Targeted therapies like c-Kit inhibitors and CD56-directed immunoconjugates offer potential new treatment avenues for SCLC.
- These novel strategies may provide additional therapeutic options for patients resistant to conventional therapies.
- Successful clinical trials could lead to the integration of these agents into treatment regimens for both resistant and previously untreated SCLC patients.
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