Special Issue "Targeting Hedgehog Signaling in Cancer"

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Signaling and Regulated Cell Death".

Deadline for manuscript submissions: 31 October 2018

Special Issue Editor

Guest Editor
Dr. Natalia Riobo-Del Galdo

Thomas Jefferson University, Department of Biochemistry and Molecular Biology, Philadelphia, United States
Website | E-Mail
Interests: signal transduction; cancer biology; Hedgehog pathway

Special Issue Information

Dear Colleagues,

The number of Hedgehog pathway publications about cancer is constantly increasing, but together with this increase, the confusion about the efficacy of targeted therapies also increases. In part, the problem is the need to identify the cancer types/subtypes that truly depend on Hedgehog signalling for proliferation, and the molecular mechanisms of that dependency, which range from mutations in Patched1 or Smoothened, upregulation of Hedgehog ligands, amplification of Gli1 or Gli2, or crosstalk with other signalling pathways that increase Gli activation.

The scope of this Special Issue is to generate a comprehensive and curated view of the types of Hedgehog-dependent cancers, the origin of that dependency, the most rational molecular targets for therapy, and the results of past or current clinical trials. The issue will review the use of Vismodegib, Sonidegib, and the other Smoothened inhibitors currently awaiting approval, the use of arsenic compounds, itraconazole, and animal experimentation with Gli inhibitors such as GANT61. It will also discuss the findings of studies supplementing vitamin D, a purported Smoothened inhibitor, and the impact of Statins use for the control of cardiovascular disease on the risk of developing Hedgehog dependent cancers. Furthermore, discussion of the alternative mechanisms of resistance to Smoothened inhibitors, as well as potential solutions, will be presented.

            We look forward to your valuable contributions.

Dr. Natalia Riobo-Del Galdo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • Hedgehog
  • Cancer
  • Smoothened inhibitors
  • Non-canonical activation of Gli
  • Efficacy and safety 
  • Mechanisms of treatment resistance

Published Papers (1 paper)

View options order results:
result details:
Displaying articles 1-1
Export citation of selected articles as:


Open AccessReview Targeting the Multidrug Transporter Ptch1 Potentiates Chemotherapy Efficiency
Received: 1 July 2018 / Revised: 8 August 2018 / Accepted: 11 August 2018 / Published: 14 August 2018
Cited by 1 | PDF Full-text (1691 KB) | HTML Full-text | XML Full-text
One of the crucial challenges in the clinical management of cancer is resistance to chemotherapeutics. Multidrug resistance (MDR) has been intensively studied, and one of the most prominent mechanisms underlying MDR is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Despite research efforts
[...] Read more.
One of the crucial challenges in the clinical management of cancer is resistance to chemotherapeutics. Multidrug resistance (MDR) has been intensively studied, and one of the most prominent mechanisms underlying MDR is overexpression of adenosine triphosphate (ATP)-binding cassette (ABC) transporters. Despite research efforts to develop compounds that inhibit the efflux activity of ABC transporters and thereby increase classical chemotherapy efficacy, to date, the Food and Drug Administration (FDA) has not approved the use of any ABC transporter inhibitors due to toxicity issues. Hedgehog signaling is aberrantly activated in many cancers, and has been shown to be involved in chemotherapy resistance. Recent studies showed that the Hedgehog receptor Ptch1, which is over-expressed in many recurrent and metastatic cancers, is a multidrug transporter and it contributes to the efflux of chemotherapeutic agents such as doxorubicin, and to chemotherapy resistance. Remarkably, Ptch1 uses the proton motive force to efflux drugs, in contrast to ABC transporters, which use ATP hydrolysis. Indeed, the “reversed pH gradient” that characterizes cancer cells, allows Ptch1 to function as an efflux pump specifically in cancer cells. This makes Ptch1 a particularly attractive therapeutic target for cancers expressing Ptch1, such as lung, breast, prostate, ovary, colon, brain, adrenocortical carcinoma, and melanoma. Screening of chemical libraries have identified several molecules that are able to enhance the cytotoxic effect of different chemotherapeutic agents by inhibiting Ptch1 drug efflux activity in different cancer cell lines that endogenously over-express Ptch1. In vivo proof of concept has been performed in mice where combining one of these compounds with doxorubicin prevented the development of xenografted adrenocortical carcinoma tumors more efficiently than doxorubicin alone, and without obvious undesirable side effects. Therefore, the use of a Ptch1 drug efflux inhibitor in combination with classical or targeted therapy could be a promising therapeutic option for Ptch1-expressing cancers. Full article
(This article belongs to the Special Issue Targeting Hedgehog Signaling in Cancer)

Graphical abstract

Back to Top