Somatostatin, Its Receptors and Analogs, in Lung Cancer

Abstract

Despite developments in diagnosis and treatment, lung cancer is the commonest cause of cancer death in Europe and North America. Due to increasing cigarette consumption, the incidence of the disease and resultant mortality is rising dramatically in women. Novel approaches to the management of lung cancer are urgently required. Somatostatin is a tetradecapeptide first identified in the pituitary and subsequently throughout the body particularly in neuroendocrine cells of the pancreas and gastrointestinal tract and the nervous system. The peptide has numerous functions including inhibition of hormone release, immunomodulation and neurotransmission and is an endogenous inhibitor of cell proliferation and angiogenesis. Somatostatin and its analogs, including octreotide (SMS 201–995), somatuline (BIM 23014) and vapreotide (RC-160), act by binding to specific somatostatin receptors (SSTR) of which there are 5 principal subtypes, SSTR-1–5. Although elevated plasma somatostatin levels may be detected in 14–15% of patients, tumor cell expression appears rare. SSTR may be expressed by lung tumors, particularly small cell lung cancer and bronchial carcinoid disease. [¹¹¹In]pentetreotide scintigraphy may have a role to play in the localization and staging of lung cancers both before and following treatment, and in detecting relapsed disease. The potential role of radiolabelled somatostatin analogs as radiotherapeutic agents in the management of lung cancer is currently being explored. Somatostatin analog therapy results in significant growth inhibition of both SSTR-positive and SSTR-negative lung tumors in vivo. Recent work indicates that these agents may enhance the efficacy of chemotherapeutic agents in the treatment of solid tumors including lung cancer.

Hypothalamic hormones a.k.a. hypothalamic releasing factors

“…Somatostatin analogs have been proposed in the treatment of these tumors, either alone particularly as high-energy radioisotope-labeled peptide (octreotide) or as adjuvant therapy. Similar observations and conclusions have been made and proposed in cases of small cell lung cancer and bronchial carcinoid disease (O'Byrne et al 2001). In fact, all so-called neural crest or neuroendocrine tumors (insulinomas, glucagonomas, gastrinomas) have been shown to express somatostatin receptors and to respond, sometimes dramatically, to long-acting analogs of somatostatin.…”

Efficacy and Safety of Carboplatin and Etoposide Combination Chemotherapy for Extrapulmonary Neuroendocrine Carcinoma: A Retrospective Case Series

“…The National Comprehensive Cancer Network Guidelines (NCCN) recommends application of chemotherapy for small-cell lung cancer in extrapulmonary NEC patients because of histopathological similarities between small-cell lung cancer and NEC [16]. A randomized controlled trial that compared cisplatin-irinotecan combination therapy with cisplatin-etoposide combination therapy for extensive small-cell lung cancer was conducted in Japan [17] and demonstrated that cisplatin-irinotecan combination therapy is more suitable for extensive disease of small-cell lung cancer than cisplatin-etoposide combination therapy.…”

Hypermethylation of the somatostatin promoter is a common, early event in human esophageal carcinogenesis

“…4 In recent years, several studies have suggested that SST functions as a tumor suppressor gene and possesses potent antitumor and antisecretory activity in several human cancers in vitro and in vivo. [5][6][7][8] Aberrant methylation of promoter CpG islands upstream of tumor suppressor genes is now well established as a major epigenetic mechanism of gene inactivation in tumorigenesis, 9 including ESCC and EAC. 10,11 More recently, data from our laboratory have shown that the SST promoter is methylated in 80% of human colon cancers, and that 5-aza-2 0 -deoxycytidine (5-Aza-dC) reverses SST promoter hypermethylation and restores SST mRNA expression in colon cancer cell lines.…”