Old Sonic Hedgehog, new tricks: a new paradigm in thoracic malignancies

Our plain-English summary of Old Sonic Hedgehog, new tricks: a new paradigm in thoracic malignancies, by E. Giroux Leprieur, D.M. Jablons, B. He (Oncotarget, 2018).

The study

• Authors: E. Giroux Leprieur, D.M. Jablons, B. He
• Journal: Oncotarget
• Published: 2018;9(18):14680-14691
• Type of article: Review
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The Sonic Hedgehog (Shh) pathway is physiologically involved during embryogenesis, but is also activated in several diseases, including solid cancers. Previous studies have demonstrated that the Shh pathway is involved in oncogenesis, tumor progression and chemoresistance in lung cancer and mesothelioma. The Shh pathway is also closely associated with epithelial-mesenchymal transition and cancer stem cells. Recent findings have revealed that a small proportion of lung cancer cells expressed an abnormal full-length Shh protein, associated with cancer stem cell features. In this paper, we review the role of the Shh pathway in thoracic cancers (small cell lung cancer, non-small cell lung cancer, and mesothelioma) and discuss the new perspectives of cancer research highlighted by the recent data of the literature.

In plain English

This was a review of published research; it did not say how studies were chosen and did not discuss asbestos. The authors described the Sonic Hedgehog (Shh) pathway in small cell lung cancer, non-small cell lung cancer and malignant pleural mesothelioma. In mesothelioma, earlier studies found Shh pathway proteins overexpressed in tumors but not in normal pleural tissue. Blocking the pathway reduced tumor growth in primary cultures and animal xenograft models; a Gli blocker acted synergistically with pemetrexed in mesothelioma cell lines. In lung cancer, one study found pathway activation in 87% of adenocarcinomas and 93% of squamous cell carcinomas among 120 samples. In small cell lung cancer, cited trials found no survival difference when vismodegib was added to chemotherapy, and a 79% response rate with sonidegib plus chemotherapy (15 patients). The authors' earlier work found a small proportion of non-small cell lung cancer cells making full-length Shh protein. They wrote that this does not seem restricted to lung cancer, as Shh-positive cells can also be found in mesothelioma. The authors concluded that Shh pathway inhibition opens a new avenue for therapies targeting cancer stem cells.

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
• Who was studied: Published laboratory, tissue and clinical studies on small cell lung cancer, non-small cell lung cancer and malignant pleural mesothelioma. The authors give no search method and no total number of reviewed studies.
• Exposure: None. The review concerns a cell signaling pathway in cancers and does not discuss asbestos or any occupational exposure.
• Main results:
  • In malignant pleural mesothelioma, the review reported that previous studies found Shh pathway proteins overexpressed in tumors, while normal pleural tissue did not express these proteins.
  • In earlier mesothelioma studies, Smo inhibition significantly decreased tumor growth in primary cultures and had anti-tumor action in animal xenograft models.
  • A cited study found that a Gli-inhibitor molecule had a synergistic cytotoxic effect with pemetrexed in mesothelioma cell lines.
  • In a cited study of 120 non-small cell lung cancer samples, 87% of adenocarcinomas and 93% of squamous cell carcinomas showed Shh pathway activation.
  • In a cited phase II trial (ECOG-1508) in advanced small cell lung cancer, adding vismodegib to chemotherapy showed no difference in progression-free or overall survival compared with chemotherapy alone.
  • In a cited phase I trial in advanced small cell lung cancer, sonidegib plus cisplatin-etoposide in 15 patients showed a 79% response rate.
  • The authors' own earlier work found that a small proportion of non-small cell lung cancer cells were Shh-positive and produced full-length Shh protein.
  • The authors wrote that full-length Shh production does not seem to be restricted to non-small cell lung cancer, because Shh-positive cells can also be found in mesothelioma, pancreatic adenocarcinoma and melanoma.
• The authors' conclusion: The authors concluded that a new avenue is beginning for therapies that target cancer stem cells through Shh pathway inhibition, and they expected clinical benefits for patients with thoracic cancers.

Topics

Medical terms in this study, explained in our Lexicon: Carcinogenesis, Lung Cancer, Mesothelioma, STEM, Small Cell Lung Cancer, Non-Small Cell Lung Cancer.

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