ingenol mebutate / Generic mfg. - LARVOL DELTA

Mechanistic study of COL6A1-mediated subchondral bone remodeling in osteoarthritis via the EPAC/RAP1 axis. (PubMed, FASEB J) - "Targeted blockade of COL6A1 can alleviate subchondral bone remodeling and OA progression in DMM model mice. Ingenol mebutate is a potential therapeutic drug."

Journal • Immunology • Osteoarthritis • Pain • Rheumatology • COL6A1

Ingenol mebutate in cancer therapy: mechanisms, clinical applications and future directions. (PubMed, Med Oncol) - "However, optimizing its safety profile and exploring advanced delivery methods are critical to expanding its clinical applications. Further studies are required to establish its long-term efficacy and potential for broader use in oncology."

Journal • Review • Actinic Keratosis • Colorectal Cancer • Dermatology • Genetic Disorders • Immune Modulation • Immunology • Metabolic Disorders • Non-melanoma Skin Cancer • Skin Cancer • Solid Tumor

High-Throughput Drug Repurposing Identifies SN-38 As a Potent Inhibitor of AML with Synergistic Effects in Combination with PARP and BCL-2 Inhibitors for Treating KMT2A-Rearranged Leukemias (ASH 2024) - "Results : High Throughput Drug Screening identified the top five most active FDA-approved drugs across 6 AML cell lines : 1) SN-38 (a topoisomerase I inhibitor and the active metabolite of irinotecan), 2) Triplotide (an NF-κB inhibitor), 3) Mitoxantrone (a topoisomerase II inhibitor), 4) Idarubicin (a topoisomerase II inhibitor), and 5) Bortezomib (a proteasome inhibitor)...Drugs that exhibited greater selectivity, meaning greater responses in KMT2Ar cell lines, included : 1) Ingenol Mebutate (a PKC inhibitor), 2) a BET bromodomain inhibitor, 3) MIK665 (an MCL1 inhibitor), 4) Prexasertib (a CHK inhibitor), and 5) Crenolanib (an FLT3/PDGFR inhibitor)...Moreover, the observed synergy with PARP and BCL-2 inhibitors reveals strategies to overcome AML resistance mechanisms to SN-38. However, rigorous preclinical and clinical studies are essential to validate its efficacy, safety, and optimal dosing regimens."

Combination therapy • IO biomarker • Acute Lymphocytic Leukemia • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Oncology • Pediatrics • T Acute Lymphoblastic Leukemia • AFF1 • FLT3 • KMT2A • MLLT3

MULTI-BIOINFORMATICS REVEALED DRUGGABLE PROTEIN NETWORK OF PROGRESSION FROM GASTRIC INTESTINAL METAPLASIA TO GASTRIC ADENOCARCINOMA (UEGW 2024) - "Computational drug repurposing of approved and investigational drugs/compounds (e.g., as found on www.clinicaltrials.gov) identified the following drugs as effective for GIM: dasatinib with or without erlotinib, nilotinib, afatinib on SRC, SM1-71 on SRC, JNJ-26483327 on EGFR, Afatinib on EGFR, ingenol mebutate on protein kinase C (PKC) family, amoxapine, benoxaprofen, avobenzone, amlexanox, alprazolam, praziquantel, ibuprofen piconol, tranilast, and restoril. The druggable protein network associated with GIM progression toward GA was identified. The distinct phenotypic patterns between GIM and GA might challenge the notion that GIM serves as the primary precancerous lesion in GA tumorigenesis rather than shares a common cause with tissue-resident stem cells. Further validation of the druggable protein network is needed for the development of a cost-effective surveillance program and preventive treatment of the GIM-to-GA progression."

IO biomarker • Breast Cancer • Gastric Adenocarcinoma • Gastric Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRCA1 • CD44 • CTNNB1 • EGFR • JUN • RBP2 • SRC

Effectiveness of Imiquimod (IMQ) in Comparison to Other Treatments in the Reduction of Actinic Keratosis Lesions (EADV 2024) - "Imiquimod of different strengths as well as comparison with other treatments such as 5-fluorouracil, photodynamic therapy, diclofenac, ingenol mebutate gel and cryotherapy were assessed. Imiquimod is a safe, accessible and effective therapy for actinic keratoses. Further studies should explore means to enhance treatment efficacy with combination therapies to reduce treatment duration and increase compliance."

Actinic Keratosis • Dermatology • Oncology • Pain • Pruritus • Squamous Cell Carcinoma

International time trends and differences in topical actinic keratosis therapy utilization. (PubMed, JAAD Int) - "High-income countries used 15.37 more grams per 1000 population of 5-fluorouracil (95% CI: 9.68, 21.05), 4.64 more grams per 1000 population of imiquimod (95% CI: 3.45, 5.83), and 0.32 more grams per 1000 population of ingenol mebutate (95% CI: 0.05, 0.60). Missing medication utilization data for some countries. High-income countries use more topical AK therapies than middle-income countries."

Journal • Actinic Keratosis • Dermatology • Oncology • Squamous Cell Carcinoma

Hydroxyurea Induced Multiple Actinic Keratoses: A Case Report (INDERCOS 2024) - "He had a background of JAK2 V617F positive PV and treated with HU, acetylsalicylic acid...The patient was diagnosed with AK again, he treated with topical 5-fluorouracil (5-FU) and photoprotection was recommended...Therapeutic strategies for AK include cryotherapy, 5-FU, ingenol mebutate, imiquimod...To prevent these complications, skin examination is recommended twice a year and patients with phototypes I-II and prolonged sun exposure should be monitored more frequently. This case underlines that AKs, a precursor of SCC in photodistributed areas, should be added to the well-known cutaneous toxicities of HU therapy"

Case report • Clinical • Actinic Keratosis • Dermatology • Genetic Disorders • Hematological Disorders • Myeloproliferative Neoplasm • Non-melanoma Skin Cancer • Polycythemia Vera • Skin Cancer • Solid Tumor • Squamous Cell Carcinoma • JAK2

First Report of Colletotrichum gloeosporioides Causing Anthracnose on Euphorbia lathyris in China. (PubMed, Plant Dis) - "It is distributed or cultivated worldwide, and the seeds of E. lathyris are the main source of ingenol, which is the precursor of Picato, the first medicine approved by USFDA for the treatment of solar keratosis (Abramovits et al...To our knowledge, this is the first report of C. gloeosporioides causing anthracnose on E. lathyris. Anthracnose may cause significant yield losses in E. lathyris production, and our results will provide experimental and theoretical basis for the management of the disease."

Journal • Actinic Keratosis • Dermatology • GAPDH

Field Cancerization Therapies for the Management of Actinic Keratosis: An Updated Review. (PubMed, Am J Clin Dermatol) - "Photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL), as well as topical treatments such as 5-fluorouracil (5-FU), diclofenac gel, piroxicam, imiquimod, and ingenol mebutate, have all shown higher efficacy than vehicle treatments...Tirbanibulin, a new topical agent approved for use in 2020, boasts a favorable safety profile in comparison with imiquimod, 5-FU, and diclofenac...Moving forward, an increasing number of studies push for standardization of outcome measures to better predict risk of future cSCC and use of more effective measures of cost to better guide patients. Here, we present an updated and comprehensive narrative review both confirming the efficacy of previously mentioned therapies as well as highlighting new approaches to PDT and discussing the use of lasers and novel topical treatments for treatment of AK."

Journal • Review • Actinic Keratosis • Dermatology • Oncology • Pain • Squamous Cell Carcinoma • Squamous Cell Skin Cancer

Identification and validation of a glycolysis-related taxonomy for improving outcomes in glioma. (PubMed, CNS Neurosci Ther) - "This study elucidates that evaluating GS is essential for comprehending the heterogeneity of glioma, which is pivotal for predicting immune cell infiltration (ICI) characterization, prognosis, and personalized immunotherapy regimens. We also explored the glycolysis-related genes ADM and IM to develop a theoretical framework for anti-tumor strategies targeting glycolysis."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • ADM

Integrating bulk and single-cell RNA sequencing data reveals epithelial-mesenchymal transition molecular subtype and signature to predict prognosis, immunotherapy efficacy, and drug candidates in low-grade gliomas. (PubMed, Front Pharmacol) - "In addition, several promising drugs, including birinapant, fluvastatin, clofarabine, dasatinib, tanespimycin, TAK-733, GDC-0152, AZD8330, trametinib and ingenol-mebutate had great potential to the treatment of high risk patients. Our research revealed non-negligible role of EMT in the TME diversity and complexity of LGG. A prognostic signature may contribute to the personalized treatment and prognostic determination."

IO biomarker • Journal • Brain Cancer • CNS Tumor • Glioma • Oncology • Solid Tumor • SLC39A1

Folliculotropism in Actinic Keratoses in Patients not Responding to Treatments: A Pilot Study. (PubMed, Acta Dermatovenerol Croat) - "Patients were considered "non-responders" if the lesions persisted after two alternated completed cycles of treatments with ingenol mebutate, imiquimod, diclofenac 3%, or 5-fluoruracil. We also suggest encouraging greater focus on FLC and its description in pathology reports. This is a preliminary observational study, but it reinforces the need to further larger clinical studies investigating the role of specific histopathologic parameters in AKs, including FLC, that may correlate with treatment outcomes."

Journal • Actinic Keratosis • Cutaneous Melanoma • Dermatology • Dermatopathology • Genetic Disorders • Melanoma • Oncology • Skin Cancer • Solid Tumor

Photodynamic Therapy for Field Cancerization in the Skin: Where Do We Stand? (PubMed, Dermatol Pract Concept) - "This review provides a thorough display of the field of PDT on cancerized skin, which will facilitate physicians in applying PDT more efficiently and intuitively."

Journal • Review • Actinic Keratosis • Dermatology • Oncology • Pain • Transplantation

PICAMEL: Prospective Study of Ingenol Mebutate for Non-invasive Lentigo Melanoma of the Face (clinicaltrials.gov) - P2 | N=20 | Completed | Sponsor: Centre Hospitalier Universitaire de Nice | Unknown status ➔ Completed

Trial completion • Melanoma • Oncology • Solid Tumor

Topical and Intralesional Immunotherapy for the Management of Skin Cancer in Special Locations: Lips and Eyelids. (PubMed, Cancers (Basel)) - "The clearance rates and potential adverse reactions of therapeutic options such as imiquimod 5%, 5-fluorouracil (5-FU), photodynamic therapy (PDT), ingenol mebutate (IM), diclofenac, intralesional methotrexate, and interferon are reviewed. Although limited by their heterogeneity and the scarcity of clinical trials, these studies point towards promising response rates and minimal adverse effects, making these treatments viable options in selected cases."

Journal • Review • Genetic Disorders • Oncology • Skin Cancer

A Review of the Efficacy of Topical Statins for Treating Disseminated Superficial Actinic Porokeratosis. (PubMed, J Drugs Dermatol) - "While in the past DSAP has been widely treated with topical diclofenac, ingenol mebutate, topical vitamin D analog, 5-fluorouracil, imiquimod, photodynamic therapy, retinoids, cryotherapy, and laser therapy, these therapies have shown limited efficacy and have caused adverse effects including inflammatory reactions, hyperpigmentation, pain, and erythema. J Drugs Dermatol. 2023;22(10):     doi:10.36849/JDD.7540."

Journal • Review • Dermatology • Pain

Topical and Intralesional Immunotherapy for Melanoma In Situ: A Review. (PubMed, Cancers (Basel)) - "The main forms of immunotherapy used are imiquimod and, to a lesser extent, intralesional interferon-α (IL-INF-α) and ingenol mebutate (IM). Also, its use as a neoadjuvant therapy before surgery was shown to reduce the final surgical defect size required to confirm negative histologic margins. In conclusion, local immunotherapy is frequently used in clinical practice and experience confirms it to be an excellent option for certain patients."

Journal • Review • Melanoma • Oncology • Solid Tumor

Invasive SCC and tirbanibulin: experience in patient with epidermodysplasia verruciformis (EADV 2023) - " We report a 37-year-old patient with EV who had performed multiple therapies (topical imiquimod, ingenol mebutate, 5-fluorouracil, PDT) for flat wart-like lesions and AKs of the frontal region, with low benefit...For these reasons, we used tirbanibulin ointment on the area of previous surgery and on the peripheral area, applying it once a day for 2 cycles of 5 days with 14 days of break between the 2 cycles... Tirbanibulin is a novel anti-proliferative and pro-apoptotic agent, recently approved to treat mild AKs on the face and scalp, with a selective action against cells that most express microtubules and its action is more effective the greater the number of mitoses. It inhibits cell growth and induces cell death and its efficacy on SCC, melanoma and other cancer lines are being studied as well. Moore et al."

Clinical • Actinic Keratosis • Bowens Disease • Dermatology • Infectious Disease • Melanoma • Oncology • Solid Tumor

Spatial transcriptomic profiling reveals unique temporal features of EMPD across diverse time points (EADV 2023) - "Materials & Skin biopsies were taken from a 63-year-old male with EMPD who had been treated with ingenol mebutate gel for a period of 1 year... Our study was conducted to demonstrate the characteristics of EMPD over different time periods after ingeol mebutate treatment. EMPD at various time points showed unique gene expressions and the genes associated with these characteristics allowed us to investigate which pathways were activated during drug treatment."

Dermatology • Inflammation

PICABAS: Study Evaluating the Efficacy and Safety of 0.05% Ingenol Mebutate (Picato® 500) in the Treatment of Basal Cell Carcinoma (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Centre Hospitalier Universitaire de Nice | Unknown status ➔ Completed

Trial completion • Basal Cell Carcinoma • Non-melanoma Skin Cancer • Oncology

Vergleichende Wirksamkeit der Behandlungen von Molluscum contagiosum: Eine systematische Übersicht und Netzwerk-Metaanalyse. (PubMed, J Dtsch Dermatol Ges) - No abstract available

Journal • Review • Dermatology

Trends in Medicare Claims and Costs for Field Therapies by Dermatologists. (PubMed, J Am Acad Dermatol) - No abstract available

Journal • Medicare • Reimbursement • US reimbursement • Actinic Keratosis • Dermatology

Invasive SCC and tirbanibulin: experience in patient with epidermodysplasia verruciformis (EADV-Sp 2023) - "There are reports of successful use of topical imiquimod, photodynamic therapy (PDT) and topical 5-fluorouracil with recurrence when treatment is discontinued...He previously applied topical imiquimod, discontinued due to systemic reaction, ingenol mebutate, 5-fluorouracil, and performed PDT with low benefits...For these reasons, we used tirbanibulin ointment on the area of previous surgery and on the peripheral area (right hemi- frontal), applying it once a day for 2 cycles of 5 days with 14 days of break between the 2 cycles...Tirbanibulin has a selective action against cells that most express microtubules and its action is, ideally, to be considered more effective the greater the number of mitoses. Based on this reasoning, we used tirbanibulin in the treatment of iSCC, not as an alternative to the surgical proposal, which always remains the first-line of therapy, but as an adjuvant approach in a selected patient to reduce the risk of progression, waiting for a..."

Clinical • Actinic Keratosis • Bowens Disease • Dermatology • Infectious Disease • Melanoma • Oncology • Solid Tumor

Comparative efficacy of treatments for molluscum contagiosum: A systematic review and network meta-analysis. (PubMed, J Dtsch Dermatol Ges) - "Ingenol mebutate, cryotherapy, podophyllotoxin, and KOH were more effective than the other interventions in achieving complete clearance, but safety concerns regarding ingenol mebutate have recently been reported. Due to the possibility of spontaneous resolution, observation is also justified for asymptomatic infection. Factors including adverse effects, cost, patient preference, and medical accessibility should be considered."

Clinical • Journal • Retrospective data • Review • Dermatology • Infectious Disease

Longitudinal integrated spatial transcriptomic profiling and single-cell RNA sequencing analysis of primary extra-mammary Paget’s disease (ISID 2023) - "Serial skin biopsies were obtained from a 63-year-old male patient diagnosed with primary EMPD and treated with ingenol mebutate for 1 year...Integration of scRNAseq and spatial transcriptomics via computational deconvolution methods revealed changes in the immune cell profile according to the time-interval along with treatment duration. Overall, these data inform on the pathomechanisms of EMPD formation and progression."

Dermatology • Oncology • Rare Diseases