The Clinical Relevance of Recent Developments in Pathology and Biology of Small Cell Lung Cancer: Monoclonal antibodies

In: Lung Cancer

16 Nov 2014

C. “Natural killer cell” antigens: In 1984 Ruff and Pert reported the presence of reactive sites on SCLC shared by specific markers for macrophages. They suggested a hemopoietic stem cell origin for SCLC. Later, the expression of certain natural killer cell antigens such as Leu-725 and NKH-l were identified. Leu-7 was demonstrated in 16/20 SCLC tumors, in occasional non-SCLC tumors (7/33) and in all the carcinoids (6/6). These antibodies seem to react with a number of neuroendocrine cells, but are apparently quite suggestive of SC IX when present in malignant lung tumors.

D. Monoclonal antibodies (MoAb) against “SCLC-anti-gens” Within recent years multiple antibodies have been raised against SCLC antigens, which have been stressed to be more or less specific for SCLC compared with the non-SC LC tumors. The interpretation of most of these data must be cautious, as the antibodies are often poorly characterized, the epitopes poorly defined, and the reproducibility of the results not confirmed in other laboratories. To coordinate the considerable amount of work in this field, and to cluster the antibodies according to their specificity and characterization, the First International Workshop on SCLC antigens was held in London 1987. The follow-up of this workshop will be of considerable clinical interest.
Today, the clinical utility of these antibodies is mainly focused on the primary diagnosis of SCLC vs non-SCLC, and in the detection of metastases, especially micrometas-tases. In the primary diagnosis of SCLC some of the antibodies seem to be of special interest,and the findings of micrometastases in the bone-marrow by the use of MoAb might be of clinical significance in the treatment planning of patients otherwise staged as having “limited” disease and in the early detection of treatment failure. The role of MoAb in the imaging of patients with SCLC is still under investigation and no significant data are yet available. in detail

Oncogenes
Studies with oncogenes in SCLC have mainly been done on the many continuous cell lines established. Considerable amplification of especially the myc-family of the protooncogenes has been recognized in cell lines (33-41) as well as in paraffin fixed SCLC tissue. Three myc-oncogenes have been demonstrated in SCLC: c-myc, n-myc, and l-myc. The demonstration of c-myc DNA amplification in tumor cell lines established from treated SCLC patients seem to be associated with shortened survival. However, a later study of myc family DNA amplification in tumor specimens obtained from SCLC patients showed that the patients, whose tumors had myc amplification did not have a remarkably different clinical course than patients with tumors in which myc amplification was not demonstrated. The role of these protooncogenes in the genesis and progression of SCLC is not at present clearified.
Growth Factors
Within recent years several hormones have been demonstrated to act as autocrine growth factors, including gastrin-releasing peptide (GRP) (“bombesin”), somatomedin C/insulin-like growth factor l, and neurotensin. A phase 1 study has been initiated with anti-GRP, but at present the dose-level of anti-GRP has not yet reached the level of expected tumor response.
Chromosome 3p-Deletion
Molecular probes have established that deletion of the short arm of chromosome 3 occurs frequently in SCLC tumors.® However, other studies have also demonstrated this abnormality to occur in non-SCLC. The clinical relevance of this finding is still awaiting the results from ongoing studies.


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