Hedgehog signaling inhibitors in solid and hematological cancers

Cortes, Jorge; Gutzmer, Ralf; Kieran, Mark W.; Solomon, James A.

doi:10.1016/j.ctrv.2019.04.005

Cited by 95 publications

(73 citation statements)

References 94 publications

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“…Interfering collagen biosynthesis enzymes Collagen genes MiR-129-5p, MiR-29b, MiR-384 [275][276][277] Prolyl 4-hydroxylase Budesonide, catechol, N-oxalylglycine, coumalic acid, ethyl dihydroxybenzoic acid [278][279][280] Heat shock protein 90 1G6-D7, dipalmitoyl-radicicol, 17-DMAG, ganetespib [281][282][283][284] Heat shock protein 47 MiR-29, 1,3-dimethylol-5-FU, AK778, pirfenidone, terutroban [285,286] Matrix metalloproteinases Gallium complex GS2, isoflavonoids, bisphosphonates [287,288] Lysyl oxidases Beta-aminopropionitrile [289] Disturbing cancer cell signaling pathways Snail transcription factors Toosendanin, ponicidin, ferulic acid [290] Hypoxia-inducible factor Tamoxifen, 28-O-propynoylbetulin [291,292] STAT3 signaling pathway VS-4718, stattic, ruxolitinib, S3I-201 [293,294] TGF-β signaling pathway LY2157299 monohydrate, trabedersen, fresolimumab, galunisertib [295,296] NF-κB signaling pathway Honokiol, aspirin, ormeloxifene [297][298][299] AKT signaling pathway Quetiapine, pirfenidone [300] Notch signaling pathway Rovalpituzumab tesirine, taladegib, crenigacestat, MiR-148a [301] Hedgehog signaling pathway Itraconazole, sonidegib, vismodegib [302] RAS signaling pathway Perindopril, losartan [100,303] Tyrosine kinase receptor Bevacizumab, imatinib, ponatinib, dasatinib [304,305] Discoidin domain receptor WRG-28, 7rh, AZD0156 [306][307][308] G protein family receptor AT13148, KD025, Azaindole 1, chelerythrine…”

Section: Effects Of Inhibitors Targeted Sites Of Inhibitors Typical Imentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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Collagen is the major component of the tumor microenvironment and participates in cancer fibrosis. Collagen biosynthesis can be regulated by cancer cells through mutated genes, transcription factors, signaling pathways and receptors; furthermore, collagen can influence tumor cell behavior through integrins, discoidin domain receptors, tyrosine kinase receptors, and some signaling pathways. Exosomes and microRNAs are closely associated with collagen in cancer. Hypoxia, which is common in collagen-rich conditions, intensifies cancer progression, and other substances in the extracellular matrix, such as fibronectin, hyaluronic acid, laminin, and matrix metalloproteinases, interact with collagen to influence cancer cell activity. Macrophages, lymphocytes, and fibroblasts play a role with collagen in cancer immunity and progression. Microscopic changes in collagen content within cancer cells and matrix cells and in other molecules ultimately contribute to the mutual feedback loop that influences prognosis, recurrence, and resistance in cancer. Nanoparticles, nanoplatforms, and nanoenzymes exhibit the expected gratifying properties. The pathophysiological functions of collagen in diverse cancers illustrate the dual roles of collagen and provide promising therapeutic options that can be readily translated from bench to bedside. The emerging understanding of the structural properties and functions of collagen in cancer will guide the development of new strategies for anticancer therapy.

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Section: Effects Of Inhibitors Targeted Sites Of Inhibitors Typical Imentioning

confidence: 99%

The role of collagen in cancer: from bench to bedside

et al. 2019

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“…On the other hand, PTCH1 has the highest FPKM value among all the genes with expression change, and the degree of its reduction almost reached one hundred folds. PTCH1 is a negative regulator of SHH signaling pathway, which is involved in oncogenesis of multiple cancers 27 and is one of the downstream pathways activated by ALK. 28,29 Basal cell carcinoma (BCC) tumors had increased expression of ALK and the genes in SHH pathway.…”

Section: Discussionmentioning

confidence: 99%

<p>Efficacy and Resistance of ALK Inhibitors in Two Inflammatory Myofibroblastic Tumor Patients with ALK Fusions Assessed by Whole Exome and RNA Sequencing</p>

Zhang¹,

Wang²,

Zhuang³

et al. 2020

OTT

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We report two inflammatory myofibroblastic tumor (IMT) patients with ALK fusions (RRBP-ALK and TNS1-ALK, respectively). They both received tumor resection surgery and treatment with ALK inhibitors crizotinib followed by alectinib, and upon receiving each of the drugs, showed a brief response, then experienced recurrence or progression of the disease. During the treatment, whole exome sequencing (WES) and RNA sequencing (RNA-Seq) were applied to monitor potential drug-induced gene mutation and expression changes. A novel, secondary mutation in ALK exon 23 (L1196Q) was identified in patient 1 after alectinib resistance developed. Guided by this result, a newer ALK inhibitor, ceritinib was prescribed. The patient was able to achieve a partial response (PR) and is in good condition as of the manuscript date. On the contrary, there was no secondary mutation identified in ALK in patient 2 after drug resistance. While the expression of PTCH1, a negative regulator of the sonic hedgehog (SHH) signaling pathway, was significantly reduced at the time after the treatment with crizotinib before that of alectinib. The expression of PTCH1 was also reduced after the treatment with alectinib. It was reported that ALK can exert its biological functions partially by activating SHH signaling pathway. The down-regulation of PTCH1 suggests the compensatory activation of SHH pathway may cause resistance to ALK inhibitors in IMT. Going forward, monitoring gene mutation and expression changes through DNA and RNA sequencing will be able to offer opportunities to investigate potential mechanisms of drug resistance and will help to achieve precise prescription for better treatment outcomes.

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“…In mammals, Hh signaling is comprise of three known ligands, Sonic hedgehog (Shh), Desert hedgehog (Dhh), and Indian hedgehog (Ihh) [ 200 ]. Inappropriate activation of the Hh signaling has been described in a variety of human cancers including pancreatic, skin, and gastrointestinal cancers [ 201 , 202 ]. The Hh signaling cascade is initiated upon binding of the Hh ligand to the PTCH receptor and subsequent inhibition of the smoothened (SMO) [ 203 ].…”

Section: Signaling Pathway-based Therapiesmentioning

confidence: 99%

Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

Lee

Hong

2020

Cancers

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The first report of cancer stem cell (CSC) from Bruce et al. has demonstrated the relatively rare population of stem-like cells in acute myeloid leukemia (AML). The discovery of leukemic CSCs prompted further identification of CSCs in multiple types of solid tumor. Recently, extensive research has attempted to identity CSCs in multiple types of solid tumors in the brain, colon, head and neck, liver, and lung. Based on these studies, we hypothesize that the initiation and progression of most malignant tumors rely largely on the CSC population. Recent studies indicated that stem cell-related markers or signaling pathways, such as aldehyde dehydrogenase (ALDH), CD133, epithelial cell adhesion molecule (EpCAM), Wnt/β-catenin signaling, and Notch signaling, contribute to the initiation and progression of various liver cancer types. Importantly, CSCs are markedly resistant to conventional therapeutic approaches and current targeted therapeutics. Therefore, it is believed that selectively targeting specific markers and/or signaling pathways of hepatic CSCs is an effective therapeutic strategy for treating chemotherapy-resistant liver cancer. Here, we provide an overview of the current knowledge on the hepatic CSC hypothesis and discuss the specific surface markers and critical signaling pathways involved in the development and maintenance of hepatic CSC subpopulations.

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Hedgehog signaling inhibitors in solid and hematological cancers

Cited by 95 publications

References 94 publications

The role of collagen in cancer: from bench to bedside

The role of collagen in cancer: from bench to bedside

<p>Efficacy and Resistance of ALK Inhibitors in Two Inflammatory Myofibroblastic Tumor Patients with ALK Fusions Assessed by Whole Exome and RNA Sequencing</p>

Targeting Liver Cancer Stem Cells: An Alternative Therapeutic Approach for Liver Cancer

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