Integrated clinical and basic studies related to circumventing non-small cell lung cancer drug resistance.
Consideration of a range of clinical and basic studies conducted at the National Cancer Institute which explore the nature of the tumor biology of lung identify the limitations of using chemotherapy for the treatment of advanced lung cancer. No single mechanistic explanation for lung cancer's chemoresistance is apparent, although considerable information about the biology of lung cancer and some of its clinical consequences have been elucidated. In contrast to previous works from our group, this presentation will focus principally on studies of the nature of drug resistance with non-small cell cancer. An alternative combined modality strategy for lung cancer control is to focus on epithelial progression of lung cancer using local modalities while it is still confined to the bronchial epithelium. Particular high risk populations may be appropriate to determine if local tools such as photodynamic laser therapy can be effective in this application. To deal with the underlying biochemical perturbations resulting from critical exposure of the bronchial epithelium to carcinogens, rational biochemical intervention with 13 cis retinoic acid are being evaluated in several clinical trials. An evolution towards more effective lung cancer control may involve the combined modalities of laser ablation of accessible dysplastic epithelium and chronic administration of intervention agents, such as retinoids, to neutralize cancer promotion dynamics in the more remote areas of the lung epithelium.
Mulshine
J L
JL
Biomarkers and Prevention Research Branch, National Cancer Institute, National Institutes of Health, Rockville, MD 20850-3300.
Johnson
B E
BE
Gazdar
A F
AF
Shaw
G L
GL
Kramer
B S
BS
Mitsudomi
T
T
Minna
J D
JD
Pass
H
H
Phelps
R
R
Ghosh
B
B
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage / Q000627:therapeutic use; D017322:Clinical Trials, Phase II as Topic; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005047:Etoposide / Q000008:administration & dosage; D006801:Humans; D015474:Isotretinoin / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D016609:Neoplasms, Second Primary; D014411:Neoplastic Stem Cells / Q000187:drug effects; D009857:Oncogenes; D010641:Phenotype; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D005047:Etoposide; D016190:Carboplatin; D015474:Isotretinoin; D002945:Cisplatin