Targeted molecules in small cell lung cancer
Section snippets
c-Kit inhibition in small cell lung cancer
Certain receptor tyrosine kinases (RTKs) are overexpressed in SCLC. The RTKs contain an N-terminal extracellular binding domain, a single transmembrane helix, and a cytosolic C-terminal domain with tyrosine kinase activity. Some RTKs are proto-oncogenes involved in alterations of reactive oxygen species; activation of downstream signal-transduction molecules; and cellular proliferation, migration, and survival, all key events in metastasis.4 Accordingly, inhibition of RTKs may be effective
Development of the immunoconjugate BB-10901 (huN901-DM1) for small cell lung cancer
BB-10901 (huN901-DM1) is an immunoconjugate tumor-activated prodrug under development for the treatment of SCLC and other neuroendocrine malignancies. A tumor-activated prodrug is a conjugate of a cytotoxin bound to an antibody. The cytotoxic component of the complex is inactive until it reaches its target site. At the target site, the conjugate binds to the tumor cell and is internalized to release the cytotoxin intracellularly. BB-10901 is an immunoconjugate consisting of the humanized
Investigation of BB-10901 for relapsed and refractory small cell lung cancer
We are conducting an ongoing phase I trial of BB-10901 for SCLC and other neuroendocrine malignancies.20 Eligible patients have SCLC that is either relapsed or refractory to prior chemotherapy. We are also enrolling patients with extrapulmonary small cell cancers and other neuroendocrine tumors, provided that CD56 positivity is confirmed. Eligible patients may have had no more than three prior chemotherapy regimens. Because of the possibility of neurotoxicity with the drug, patients with a
Conclusions
As the understanding of the molecular basis of SCLC increases, changes in the natural history of this cancer become possible with treatments using a combination of cytotoxic chemotherapy and target-specific drugs. Tailoring therapy based on genetic or protein expression profiles of individual tumors is likely to be a requirement in this anaplastic tumor. Disruption of signal-transduction pathways such as the c-Kit autocrine loop with a tyrosine kinase inhibitor and creation of an
References (20)
- et al.
Molecular pathogenesis of lung cancer
J Thorac Cardiovasc Surg
(1999) - et al.
Molecular and cellular biology of small cell lung cancer
Semin Oncol
(2003) - et al.
Selective Sp1 binding is critical for maximal activity of the human c-kit promoter
Blood
(1998) - et al.
Overview of rationale and clinical trials with signal transduction inhibitors in lung cancer
Semin Oncol
(2002) - et al.
NCAMA surface marker for human small cell lung cancer cells
FEBS Lett
(1990) - et al.
The epidemiology of small cell lung carcinoma
Proc Am Soc Clin Oncol
(2002) - et al.
Molecular abnormalities in lung cancer
J Clin Oncol
(1998) - et al.
Growth inhibition and modulation of kinase pathways of small cell lung cancer cell lines by the novel tyrosine kinase inhibitor STI 571
Oncogene
(2000) - et al.
Lck associates with and is activated by Kit in a small cell lung cancer cell lineInhibition of SCF-mediated growth by the Src family kinase inhibitor PP1
Cancer Res
(1998) - et al.
Inhibition of KIT tyrosine kinase activityA novel molecular approach to the treatment of KIT-positive malignancies
J Clin Oncol
(2002)
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Dr Murray has received honoraria and served as a consultant to AstraZeneca Pharmaceuticals, LP, and Aventis Oncology. Dr Fossella has received research grant support from British Biotech.