Improving the Efficacy of EGFR Inhibitors by Topical Treatment of Cutaneous Squamous Cell Carcinoma with miR-634 Ointment

Inoue, Jun; Fujiwara, Kyoko; Hamamoto, Hidetoshi; Kobayashi, Katsunori; Inazawa, Johji

doi:10.1016/j.omto.2020.10.009

Cited by 19 publications

(38 citation statements)

References 62 publications

(44 reference statements)

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“…A Japanese group studied the effectiveness of a topical ointment with microRNA (miRNA) 634 combined with a systemic EGFR inhibitor in vitro and then in vivo on mice. If the findings of this study are confirmed in human studies, this combination therapy may become an alternative for cutaneous SCC ineligible for surgery [ 44 ].…”

Section: Discussionmentioning

confidence: 85%

Local Chemotherapy as an Adjuvant Treatment in Unresectable Squamous Cell Carcinoma: What Do We Know So Far?

Bennardo

Giudice

et al. 2021

Current Oncology

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Background: Squamous cell carcinoma (SCC) is one of the most common cancers involving skin and oral mucosa. Although this condition’s gold-standard treatment is the surgical removal of the lesions, the physician must propose alternative treatments in some cases due to the patient’s ineligibility for surgery. Among the available alternative therapies, local chemotherapy may represent an initial treatment in combination with radiotherapy or systemic chemotherapy due to the low frequency of side-effects and the lack of necessity for expensive devices. Methods: In this paper, we review all available literature in various databases (PubMed, Scopus-Embase, Web of Science), proposing local chemotherapy as a treatment for cutaneous and oral SCC. Exclusion criteria included ocular lesions (where topical treatments are common), non-English language, and non-human studies. Results: We included 14 studies in this review. The majority were case reports and case series describing the treatment of non-resectable localized SCC with either imiquimod or 5-fluorouracil. We also analyzed small studies proposing combination treatments. Almost all studies reported an excellent clinical outcome, with a low risk of relapses in time. Conclusions: Resection of the lesion remains the gold-standard treatment for SCC. When this approach is not feasible, local chemotherapy may represent a treatment alternative, and it may also be associated with radiotherapy or systemic chemotherapy.

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Section: Discussionmentioning

confidence: 85%

Local Chemotherapy as an Adjuvant Treatment in Unresectable Squamous Cell Carcinoma: What Do We Know So Far?

Bennardo

Giudice

et al. 2021

Current Oncology

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“…Cells (1 × 10 4 cells/well) were plated in 96‐well plates and siRNA was transfected the next day at 10 nmol/L using Lipofectamine RNAiMAX (Thermo Fisher Scientific) according to the manufacturer's instructions. After 3 days, cells were stained with 0.1% crystal violet (CV) as described in previous papers 25,26 . The stained cells were lysed with a 2% SDS solution and the optical density (OD) was measured at 560 nm using a microplate reader.…”

Section: Methodsmentioning

confidence: 99%

“…After 3 days, cells were stained with 0.1% crystal violet (CV) as described in previous papers. 25,26 The stained cells were lysed with a 2% SDS solution and the optical density (OD) was measured at 560 nm using a microplate reader. The OD values of cells relative to the control cells transfected with pooled siRNA for the negative control (siNC) were arbitrarily set to 100% to determine the percentage of viable cells.…”

Section: Construction Of the Sirna Library And Cell Growth Assaymentioning

confidence: 99%

Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma

et al. 2021

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The metabolism in tumors is reprogrammed to meet its energetic and substrate demands. However, this metabolic reprogramming creates metabolic vulnerabilities, providing new opportunities for cancer therapy. Metabolic vulnerability as a therapeutic target in esophageal squamous cell carcinoma (ESCC) has not been adequately clarified. Here, we identified pyruvate dehydrogenase (PDH) component X (PDHX) as a metabolically essential gene for the cell growth of ESCC. PDHX expression was required for the maintenance of PDH activity and the production of ATP, and its knockdown inhibited the proliferation of cancer stem cells (CSCs) and in vivo tumor growth. PDHX was concurrently upregulated with the CD44 gene, a marker of CSCs, by co‐amplification at 11p13 in ESCC tumors and these genes coordinately functioned in cancer stemness. Furthermore, CPI‐613, a PDH inhibitor, inhibited the proliferation of CSCs in vitro and the growth of ESCC xenograft tumors in vivo. Thus, our study provides new insights related to the development of novel therapeutic strategies for ESCC by targeting the PDH complex‐associated metabolic vulnerability.

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“…There are also convincing examples of topical skin cancer treatment with oligonucleotides that validate the possibility of using miRNAs in treating this type of cancer [43]. Inoue et al demonstrated that using a topical ointment containing miR-634 inhibited in vivo tumor growth without toxicity in two different skin tumor models: a cSCC xenograft mouse model and 7,12-dimethylbenz[a]anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA)-induced papilloma mouse model [44].…”

Section: Local Deliverymentioning

confidence: 97%

microRNAs as Novel Therapeutics in Cancer

Romano

Acunzo

Nana‐Sinkam

2021

Cancers

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In the last 20 years, the functional roles for miRNAs in gene regulation have been well established. MiRNAs act as regulators in virtually all biological pathways and thus have been implicated in numerous diseases, including cancer. They are particularly relevant in regulating the basic hallmarks of cancer, including apoptosis, proliferation, migration, and invasion. Despite the substantial progress made in identifying the molecular mechanisms driving the deregulation of miRNAs in cancer, the clinical translation of these important molecules to therapy remains in its infancy. The paucity of vehicles available for the safe and efficient delivery of miRNAs and ongoing concerns for toxicity remain major obstacles to clinical application. Novel formulations and the development of new vectors have significantly improved the stability of oligonucleotides, increasing the effectiveness of therapy. Furthermore, the use of specific moieties for delivery in target tissues or cells has increased the specificity of treatment. The use of new technologies has allowed small but important steps toward more specific therapeutic delivery in tumor tissues and cells. Although a long road remains, the path ahead holds great potential. Currently, a few miRNA drugs are under investigation in human clinical trials with promising results ahead.

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Improving the Efficacy of EGFR Inhibitors by Topical Treatment of Cutaneous Squamous Cell Carcinoma with miR-634 Ointment

Cited by 19 publications

References 62 publications

Local Chemotherapy as an Adjuvant Treatment in Unresectable Squamous Cell Carcinoma: What Do We Know So Far?

Local Chemotherapy as an Adjuvant Treatment in Unresectable Squamous Cell Carcinoma: What Do We Know So Far?

Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma

microRNAs as Novel Therapeutics in Cancer

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