Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets

Our plain-English summary of Molecular genetics and mechanisms of apoptosis in carcinomas of the lung and pleura: therapeutic targets, by L.R. Motadi, N.L. Misso, Z. Dlamini, et al (International Immunopharmacology, 2007).

The study

• Authors: L.R. Motadi, N.L. Misso, Z. Dlamini, K.D. Bhoola
• Journal: International Immunopharmacology
• Published: 2007;7(14):1934-47
• Type of article: Review
• Cited by: 21 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Cancers of the lung and pleura remain a major cause of cancer deaths, both in men and women, with strong causal relationships between cigarette smoking and asbestos fibres, and deaths from lung cancer and mesothelioma, respectively. The poor survival rates for small cell lung cancer and mesotheliomas argue powerfully for greater understanding of mechanisms of carcinogenesis, genetic abnormalities and the role of tumour suppressor genes and proteins in carcinomas of the lung and pleura. Despite progress in the development of newer cytotoxic drugs, lung cancer remains a lethal disease. Chemotherapy and radiotherapy produce only a modest improvement in survival of patients with advanced disease. Increased knowledge of molecular mechanisms of lung cancer and apoptosis are providing opportunities for treating lung cancer with new classes of molecularly targeted drugs. These novel therapies should target the abnormalities in lung cancer by maximizing the effects of anti-tumour molecules, with minimal side effects on normal tissues. Of the several molecular targets, those receiving attention are p53 gene replacement, Bcl-2 downregulation, apoptosis by induced by TNF, the FAS/CD95 receptor system and TRAIL, and inhibition of NF-kappaB. Although several studies have shown benefits, there is a need for well planned clinical trials of drugs that target the apoptotic cascade. Stem cell therapy and gene replacement offer the prospect of novel approaches that are likely in the near future to play a definitive role in the treatment of advanced lung cancer. Furthermore, with their apparent minimal toxicity to normal tissues, the newer molecular targets represent attractive investigational directions for innovative cancer therapies.

In plain English

This article was a narrative review, not an original study. It reported no new patients, measurements or experiments, and it did not describe how the published research it discussed was chosen. The authors summarized earlier work on the genetics of lung cancer and of malignant mesothelioma of the pleura, and on apoptosis, the process by which cells are programmed to die. As background, they described mesothelioma as linked to asbestos exposure, particularly crocidolite, and, citing another study, described crocidolite as 5 times more dangerous than amosite. They described a latent period of 15 to 40 years between exposure and symptoms, and survival of 5 to 16 months, for mesothelioma. Most of the review covered lung cancer. It discussed genes such as p53, which earlier studies cited by the authors found mutated in almost 90% of small cell and 50% of non-small cell lung cancers. It also discussed possible drug targets including Bcl-2, TNF, Fas, TRAIL and NF-kappaB. The authors concluded that the most promising treatment approaches for lung cancer are likely to be those that target apoptotic pathways.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research on the molecular genetics and apoptosis mechanisms of lung and pleural cancers as therapeutic targets. No original data and no stated method for selecting literature.
• Who was studied: No study population. The review discussed published laboratory, animal and clinical research on lung cancers (small cell and non-small cell) and malignant mesothelioma.
• Exposure: No exposure was studied. As background, the authors stated that mesothelioma is linked to asbestos exposure (particularly crocidolite) and, citing another study (reference 17), that crocidolite is 5 times more dangerous than amosite. Cigarette smoking was described as the major cause of lung carcinoma.
• Main results:
  • Background description, not a finding of this article: mesothelioma has a latent period of 15 to 40 years between exposure and onset of symptoms. Survival ranges from 5 to 16 months, with 75% of patients dying within one year of diagnosis.
  • Background description: the authors reported mesothelioma histological subtypes as epitheloid (50%), sarcomatous (15 to 20%), biphasic (15 to 20%) and desmoplastic (15 to 20%), citing another source.
  • Citing another study (reference 34), the review reported loss of heterozygosity in malignant mesotheliomas at several chromosome regions.
  • Citing other studies (references 42 and 43), the review reported p53 mutations in almost 90% of small cell lung cancers (SCLC) and 50% of non-small cell lung cancers (NSCLC).
  • Among the treatment targets reviewed for lung cancer, the authors reported that antisense targeting of Bcl-2 had reached phase III clinical trials for several cancers. They reported that lung cancer appears resistant to apoptosis induced by TRAIL.
• The authors' conclusion: The authors concluded that the most promising therapeutic approaches for lung cancer are likely to be those aimed at eliminating cancer cells by targeting apoptotic pathways.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Apoptosis, Carcinoma, Pleura, Lung Cancer, Mesothelioma, Small Cell Lung Cancer, Carcinogenesis, Chemotherapy.

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