Application of cantharidin, retinoic acid cream and salicylic acidy in multiple palmoplantar warts.

OBJECTIVE: Multiple palmoplantar warts, caused by human papillomavirus (HPV) infection, were investigated for clinical efficacy using cantharidin, retinoic acid cream, and salicylic acid cream. METHODS: A total of 110 patients with multiple palmoplantar warts were enrolled. The experimental group (54 cases) received a 1:1:1 combination (CRS) of 0.25% cantharidin, 0.1% retinoic acid cream, and 5% salicylic acid, applied with pressurized encapsulation for 8 h every night, three times per week. The control group (56 cases) underwent conventional liquid nitrogen freezing. Monthly follow-ups assessed cure rate, effective rate, dermatological life quality index (DLQI), visual analog scale (VAS), and cost, with evaluations conducted after 3 months. RESULTS: The treatment group exhibited a cure rate of 85.19% and a total effective rate of 96.30%, surpassing the control group with rates of 39.29% and 51.79%, respectively (p < 0.05). The treatment group's DLQI score (1.84 ± 1.06) was significantly lower than the control group's score (6.04 ± 1.78) (p = 0.0005). Additionally, the treatment group's VAS score (1.84 ± 1.06) was notably lower than the control group's score (8.56 ± 1.07) (p < 0.0001). The treatment group's total cost (43.20 ± 2.85) was markedly lower than the control group's cost (206.38 ± 90.81), with a statistically significant difference (p < 0.0001). CONCLUSION: The combination of cantharidin, retinoic acid cream, and salicylic acid with local encapsulation is a safe, effective, economical, and convenient treatment method for multiple palmoplantar warts, exhibiting few side effects and showing promise.

Cantharidin Topical Solution 0.7%: First Approval.

Cantharidin (YCANTH™) is a proprietary drug-device combination product containing a formulation of cantharidin 0.7% topical solution (a vesicant naturally derived from blister beetles) delivered via a single-use applicator that has been developed by Verrica Pharmaceuticals Inc. for the treatment of molluscum contagiosum and is also being developed for the treatment of warts. In July 2023, YCANTH™ (cantharidin 0.7% topical solution) was approved for the topical treatment of molluscum contagiosum in adult and pediatric patients 2 years of age and older in the USA. This article summarizes the milestones in the development of cantharidin 0.7% topical solution leading to this first approval for the topical treatment of molluscum contagiosum in adult and pediatric patients 2 years of age and older.

YCANTHTM (Cantharidin) Topical Solution.

YCANTHTM (cantharidin) topical solution has been approved recently for the treatment of molluscum contagiosum (MC) in children (aged ≥2 years) and adults. It works by activating serine proteases that lead to blistering and inflammation, promoting shedding of infected cells and viral clearance. In two phase-3, randomized, double-blind, vehicle-controlled trials of similar design, VP-102 (a drug-device combination, containing cantharidin 0.7% w/v and inactive ingredients, such as gentian violet, acetone, and denatonium benzoate, administered with an applicator) was investigated for the treatment of MC. VP-102 and vehicle were applied topically once every 21 days until complete clearance of lesions was observed, or for up to four treatments. Cantharidin demonstrated efficacy in achieving the primary outcome, at day 84/visit 4 (Cantharidin Application in Molluscum Patients [CAMP-1], VP-102: 46% [73/160], vehicle: 18% [19/106]; and CAMP-2, VP-102: 54% [81/150], vehicle: 13% [15/112]). Common adverse events were mild to moderate, such as lesions at the site of application, pruritus, and pain. The recommended regimen of cantharidin topical solution is its application once every 21 days until complete clearance of lesions is observed, or up to four treatments.

Endoplasmic reticulum stress contributes to autophagy and apoptosis in cantharidin-induced nephrotoxicity.

Mylabris, as a natural product of traditional Chinese medicine (TCM), exhibiting typical antitumor activity, and cantharidin (CTD) is the major bioactive component. However, drug-induced nephrotoxicity (DIN) extremely limited its clinical application. In this study, we proved that activation of the endoplasmic reticulum (ER) stress-dependent PERK/CHOP pathway exerts a toxic role in rats and HK-2 cells through inducing autophagy and apoptosis. Results showed that CTD could cause renal function damage, cytotoxicity, and apoptosis. The ER dilatation and autolysosomes were observed after CTD treatment. Furthermore, the distribution of LC3, ATF4, and CHOP proteins was observed in the nucleus and cytoplasm. In addition, the mRNA levels of ER stress-regulated genes (PERK, eIF2α, CHOP, and ATF4) were increased, and the expression levels of GRP78, ATF4, CHOP, LC3, Beclin-1, Atg3, Atg7, Caspase 3, and Bax/Bcl-2 proteins were increased both in vitro and in vivo. Consistently, this upregulation could be inhibited by an ER stress inhibitor 4-Phenylbutyric acid (4-PBA), indicating that ER stress is partly responsible for activation of autophagy and apoptosis in CTD-induced DIN. In conclusion, CTD could induce DIN by triggering ER stress, further activating autophagy and apoptosis both in vivo and in vitro.

Phase II, Double-Blind, Vehicle-Controlled Study to Determine the Cantharidin Dose Regimen, Efficacy, Safety, and Tolerability of VP-102 in Subjects with External Genital Warts.

BACKGROUND: External genital warts are caused by various subtypes of the human papilloma virus and spread through direct skin-to-skin contact. Approximately 1% of the US population have external genital warts. Although cantharidin has been used to treat external genital warts for decades, there are no US Food and Drug Administration-approved cantharidin products and no reliable or controlled sources of cantharidin available. VP-102 is a drug-device combination product containing cantharidin (0.7% w/v) in a single-use shelf-stable applicator. OBJECTIVE: The objective of this randomized, double-blind, vehicle-controlled, phase II clinical trial was to determine the optimal regimen for the treatment, safety, and efficacy of VP-102 in external genital warts. METHODS: The study was conducted in two parts. Part A was dose finding and Part B was performed following the completion of Part A for a safety and efficacy evaluation. Following completion of Part A, 6-h and 24-h VP-102 regimens under occlusion were selected to be evaluated in Part B. RESULTS: Pooled results from Part B and Part A of the 6-h and 24-h VP-102 treatment regimens showed that 36.7% and 33.3% of participants achieved complete clearance of all treatable external genital warts at the end of treatment vs 4.2% (p < 0.0048) and 0% (p < 0.0075) with the vehicle. Adverse events experienced by the VP-102-treated participants were consistent with the pharmacodynamic action of cantharidin as a vesicant and were primarily mild to moderate in severity. The most common adverse events included application-site vesicles, pain, and erythema. No participants discontinued the study because of adverse events and no serious adverse events were deemed treatment related. CONCLUSIONS: The adverse event profile and efficacy of VP-102 under occlusion demonstrated in this study support the conclusion that a 6-h or up to 24-h exposure regimen represents an acceptable risk:benefit profile and justifies the conduct of a larger vehicle-controlled phase III study in external genital warts. CLINICAL TRIAL REGISTRATION: NCT03981822, actual study start date: 25 June, 2019; actual primary completion date: 21 May, 2020; actual study completion date: 8 July, 2020.

Protective mechanism of Astragalus Polysaccharides against Cantharidin-induced liver injury determined in vivo by liquid chromatography/mass spectrometry metabolomics.

Cantharidin (CTD) is a promising anticancer drug; however, its dosage is limited by hepatotoxicity. We previously showed that Astragalus polysaccharides (APS) effectively improved chemical liver injury. In this study, we established a CTD-induced subacute liver injury mouse model and examined the effects of APS on weight, liver indexes, histopathology, serum biochemical indexes and liver metabolism. Compared with the control group, mice in the CTD model group had obvious liver damage, which was partially prevented by APS. Metabolomics demonstrated that CTD caused liver damage mainly by regulating glycerophospholipid metabolism, ABC transporter pathways and choline metabolism in cancer in vivo. APS regulated primary bile acid biosynthesis and glycerophospholipid metabolism, thus decreasing the liver damage caused by CTD. This study revealed the protective mechanism of APS against CTD-induced liver injury from the perspective of metabolomics. The results provide an important basis for analysing the mechanism of CTD-induced liver toxicity and for assessing clinical treatment options to reduce CTD liver toxicity.

Pooled Results of Two Randomized Phase III Trials Evaluating VP-102, a Drug-Device Combination Product Containing Cantharidin 0.7% (w/v) for the Treatment of Molluscum Contagiosum.

BACKGROUND: Compounded cantharidin has been used for decades to treat molluscum contagiosum but lacks rigorous clinical evidence to support its safety and efficacy. VP-102 is a shelf-stable drug-device combination product that contains topical cantharidin (0.7% weight/volume [w/v]) and is being evaluated for the treatment of molluscum. OBJECTIVES: Our objective was to present pooled safety and efficacy analyses of VP-102 in the treatment of molluscum compared with vehicle. METHODS: Participants aged ≥ 2 years were randomized 3:2 to topical administration of VP-102 or vehicle in two randomized, double-blind, vehicle-controlled phase III trials. Study drug was applied to all baseline and new lesions once every 21 days until clear or for a maximum of four applications. Assessors blinded to treatment counted all lesions at each study visit. All adverse events (AEs) were documented. Data were pooled for analyses. RESULTS: In total, 310 participants received VP-102 and 218 received vehicle. Mean age was 7.5 years (range 2-60) for VP-102 and 6.8 (2-54) for vehicle. Complete clearance of all molluscum lesions at day 84 occurred in 50% of VP-102 participants and 15.6% of vehicle recipients (p < 0.0001). Mean molluscum lesion counts decreased 76% for VP-102 and 0.3% for vehicle at day 84 (p < 0.0001). The most common AEs in the VP-102 group were application site blistering, pruritus, pain, and erythema, which were generally mild or moderate in severity. CONCLUSIONS: Pooled analyses showed a significantly higher percentage of participants with complete molluscum lesion clearance and larger reductions in lesion counts with VP-102 than with vehicle. AEs were anticipated because of the pharmacodynamic properties of cantharidin. TRIAL REGISTRATION: ClinicalTrials.gov identifiers: NCT03377790 (first posted 19 December 2017) and NCT03377803 (first posted 19 December 2017). Video abstract: Pooled Results of Two Randomized Phase III Trials Evaluating VP 102, a Drug Device Combination Product Containing Cantharidin 0.7% (w/v) for the Treatment of Molluscum Contagiosum (MP4 131293 KB).

A Phase 2 Open-Label Study to Evaluate VP-102 for the Treatment of Molluscum Contagiosum.

BACKGROUND: This Phase 2, open-label study evaluated the safety, efficacy, systemic exposure, and impact on quality of life (QoL) with treatment using VP-102, a drug-device combination containing cantharidin (0.7% w/v) in subjects with molluscum contagiosum (MC). STUDY DESIGN: Pediatric subjects with MC (2–15 years of age) were eligible to enroll in this 12-week study. MC lesions were treated topically with VP-102 every 21 days until clearance (maximum of 4 treatments). Adverse events (AEs) and QoL outcomes (using the Children's Quality of Life Index, CDLQI) were documented at each visit. Rate of complete clearance and the percent reduction in lesions were measured at each visit on days 21, 42, 63, and 84 (end of study [EOS] visit). A group of 17 subjects with at least 21 MC lesions was evaluated for systemic cantharidin exposure via plasma samples obtained before the first application of VP-102, and at 2 hours, 6 hours, and 24 hours post-application. RESULTS: A total of 33 subjects enrolled in the study (n=17 systemic exposure group, n=16 standard group). There were an equal number of male and female subjects. Subject mean (SD, range) age was 6.7 (3.3, 2–15) years, with a mean lesion count of 30 (26.1, 3–113). Complete lesion clearance was achieved in 48.5% of subjects, with a 90.4% reduction in lesions from baseline to the EOS visit. Mean CDLQI score decreased from 2.6 at baseline to 0.38 at the EOS visit. AEs were mild to moderate in severity and expected due to the pharmacodynamic action of cantharidin. There were no serious treatment-related adverse events and no study discontinuations due to treatment. In the systemic exposure group plasma cantharidin levels were below the lower limit of quantitation (LLOQ, 2.5 ng/mL) in 65 of 66 samples. CONCLUSIONS: VP-102 treatment resulted in a reduction in lesion counts and improved QoL. Treated subjects had a 48.5% rate of complete clearance of molluscum lesions. Negligible systemic cantharidin exposure was observed in the systemic exposure group. This data demonstrates safety and efficacy of treatment with VP-102 in MC; a widespread viral infection that does not have any current FDA-approved treatments. Significant Finding: Treatment of subjects with MC using VP-102 resulted in negligible systemic cantharidin exposure, as well as a reduction in lesion counts, improved QoL, and a demonstrated efficacy in clearance of new and baseline MC lesions. Meaning: Results of this Phase 2 study demonstrate efficacy and safety outcomes in using VP-102 in MC subjects, and large randomized clinical trials are warranted to compare topical VP-102 with a vehicle control in order to fully evaluate the use of the medication. ClinicalTrials.gov identifier: NCT03186378 J Drugs Dermatol. 2021;20(1):70-75. doi:10.36849/JDD.5626.

Blister beetle dermatitis caused by cantharidin in South Sudan in Op TRENTON: a case series.

Cantharidin-producing blister beetles are found worldwide. The pathognomonic feature of their toxin is a blistering dermatitis that presents an environmental health hazard. Cutaneous exposure to cantharidin can produce blistering dermatitis, most commonly seen on exposed skin, in the Bentiu region of South Sudan. This should be treated with appropriate cleaning, debridement and regular dressing changes to cope with extensive initial exudate. The best dressing combinations found were initial treatment with povidone-iodine and hydrocolloid, followed by hydrocolloid only. Hydrocolloid dressings were found to be the most effective at staying in place with South Sudan's high humidity. Prevention strategies should include covering exposed skin, wearing wide-brimmed hats, neck scarves and enclosed footwear, and avoidance of working under white light. Medical personnel should engage with the chain of command to include appropriate force protection education within the arrivals brief.

Safety and Efficacy of VP-102, a Proprietary, Drug-Device Combination Product Containing Cantharidin, 0.7% (w/v), in Children and Adults With Molluscum Contagiosum: Two Phase 3 Randomized Clinical Trials.

Importance: Molluscum contagiosum (MC) is a common viral skin infection that primarily affects children. Cantharidin, a topical vesicant, has a long history of use for MC in compounded formulations, but the safety and efficacy of doses, regimens, and application methods have not been demonstrated in large-scale trials. Objective: To determine the safety and efficacy of VP-102, a drug-device combination containing cantharidin, 0.7% (w/v), compared with vehicle in individuals with MC. Design, Setting, and Participants: Two phase 3, randomized, double-blind, vehicle-controlled trials of identical design (Cantharidin Application in Molluscum Patients [CAMP-1 and CAMP-2]) were conducted in 31 centers across the US. A total of 528 individuals aged 2 years or older with MC participated. CAMP-1 was conducted from March 21 to November 26, 2018, and CAMP-2 was conducted from February 14 to September 26, 2018. Interventions: Participants were randomized (3:2) to topical application of VP-102 or vehicle to all treatable lesions every 21 days until complete lesion clearance or up to 4 treatments. Main Outcomes and Measures: The primary efficacy outcome was the proportion of VP-102-treated participants achieving complete clearance of all MC lesions (baseline and new) compared with those who received the vehicle at the end-of-study visit on day 84. Intent-to-treat analysis was conducted for the efficacy population. Secondary efficacy outcomes included the proportion of participants achieving complete clearance of lesions at days 21, 42, and 63. Safety outcomes included assessment of adverse events, including expected local skin reactions. Results: Of the 528 participants enrolled, 527 received treatment (CAMP-1, n = 265; CAMP-2, n = 262). A total of 267 of 527 participants (50.7%) were male; mean (SD) ages for CAMP-1 and CAMP-2 were 7.5 (5.3) years and 7.4 (8.0) years for the VP-102 groups and 6.3 (4.7) years and 7.3 (6.7) years for the vehicle groups. Treatment with VP-102 demonstrated superior efficacy to vehicle in the percentage of participants with complete clearance of MC lesions at the end of the study visit for CAMP-1 (VP-102: 46.3% vs vehicle: 17.9%; P < .001) and CAMP-2 (VP-102: 54.0% vs vehicle: 13.4%; P < .001). Adverse events were observed in 99% (CAMP-1) and 95% (CAMP-2) of VP-102-treated participants and 73% (CAMP-1) and 66% (CAMP-2) of vehicle-treated participants. The most common adverse events included application site vesicles, pain, pruritus, erythema, and scab. Most adverse events were mild or moderate in severity. Conclusions and Relevance: In the 2 phase 3 trials reported herein, VP-102 was statistically significantly superior to vehicle in achieving complete clearance of MC lesions at the end of the study visit in both trials, with adverse events that were generally mild to moderate and confined to application sites. These findings show that VP-102 is potentially an effective and safe treatment for MC, a common skin condition with no US Food and Drug Administration-approved treatments. Trial Registrations: ClinicalTrials.gov Identifiers: NCT03377790 and NCT03377803.

A comparative study of topical cantharidin and intralesional PPD to treat molluscum contagiosum.

Background: The immune system plays an important part in the clearance of molluscum contagiosum (MC) and, therefore, there has lately been a trend in using immunotherapy in MC therapy. Tuberculin-purified protein derivatives (PPDs) and topical cantharidin have not earlier been compared with their effectiveness in therapyAim: The aim of this research was to determine the effectiveness and security of intralesional immunotherapy in the therapy of MC with tuberculin PPD versus topical cantharidinPatients and methods: Twenty patients with various MC lesions received topical cantharidin as control (group A) and 20 MC patients received intralesional tuberculin PPD following prior intradermal immunity tests (group B ).Results: Complete clearance of lesions was detected in 90.0% of patients in the cantharidin group; the partial response was detected in10.0% of the patients. However, in the PPD group, 85% of the patients showed a complete response and 15% showed a partial response, with no significant difference in the clinical response between the two groups. Mild side effects were detected .Conclusion: The results suggest that intralesional PPD and topical cantharidin 0.7% are effective and safe treatment modalities, but benefits of intralesional PPD is being a simple, effective and safe treatment with tolerable pain and can be an alternative treatment for multiple resistant types .

Real-life treatment of cutaneous warts with cantharidin podophyllin salicylic acid solution.

Patients often request treatment of their burdensome cutaneous warts. However, a safe and effective treatment for cutaneous warts is lacking. This study evaluates treatment outcome, side effects, and patient satisfaction after topical application of cantharidin 1% podophyllin 2% salicylic acid 30% (CPS1) solution in a large series of children and adults with cutaneous warts. Fifty-two children and 83 adults with warts, treated with CPS1 solution between October 2012 and October 2014, were included. Complete clearance of warts occurred in 86.5% of children and 62.7% of adults treated with CPS1 solution (p < .01). Resolution of warts was partial in 3.9 and 24.1% and absent in 9.6 and 13.2% of children and adults respectively. Side effects were present in 41.2% of children and 46.3% of adults (p = .7). Most common side effects were blistering, pain, and burning sensation. No serious adverse events occurred. On a 10-point scale, median patient satisfaction score was 9.0 (interquartile range 7.8-10.0) and 8.0 (interquartile range 5.1-9.7) for children and adults respectively (p < .01). CPS1 solution is a safe and promising treatment modality with a high clearance and high patient satisfaction rate for the management of cutaneous warts, particularly in children.

Efficacy and safety of sodium cantharidinate and vitamin B6 injection for the treatment of digestive system neoplasms: a meta-analysis of randomized controlled trials.

OBJECTIVE: To systematically evaluate the efficacy and safety of sodium cantharidinate and vitamin B6 (SC/B6) combined with conventional medical treatment (CMT) for the treatment of patients with advanced digestive system neoplasms (DSNs). METHODS: The Cochrane Library, Embase, PubMed, Web of Science, Chinese Scientific Journal Database (VIP), China National Knowledge Infrastructure, and Wanfang databases were searched for clinical trials using SC/B6 for DSNs. Outcome measures, including therapeutic efficacy, quality of life (QoL), and adverse events, were extracted and systematically evaluated. RESULTS: Data from 24 trials including 1,825 advanced DSN patients were included. Compared with CMT alone, its combination with SC/B6 significantly improved the patients' overall response rate (OR =2.25, 95% CI =1.83-2.76, P<0.00001), disease control rate (OR =2.41, 95% CI =1.85-3.15, P<0.00001), and QoL improvement rate (OR =2.75, 95% CI =2.13-3.55, P<0.00001). Moreover, adverse events caused by chemotherapy, including leukopenia, nausea and vomiting, gastrointestinal side effects, hepatotoxicity, diarrhea, transaminase disorder, myelosuppression, anorexia, and anemia, were significantly alleviated (P<0.05) when SC/B6 was applied to DSN patients. Nephrotoxicity, thrombocytopenia, hand-foot syndrome, and oral mucositis were not significantly alleviated in patients receiving combination therapy (P>0.05). CONCLUSION: The combination of SC/B6 and CMT is more effective in treating DSNs than CMT alone. This combination alleviates the adverse effects associated with chemotherapy and improves the QoL of DSN patients, and its application in the clinic is worth promoting.

Safety and efficacy of topical cantharidin for the treatment of pediatric molluscum contagiosum: a prospective, randomized, double-blind, placebo-controlled pilot trial.

Topical cantharidin is a commonly used treatment for molluscum contagiosum (MC). However, studies validating its safety and efficacy are limited. We conducted a 6-week, randomized, double-blind, placebo-controlled trial with subsequent open-label extension to assess the safety and effectiveness of cantharidin in treating pediatric MC. Ninety-four participants with MC were randomized to receive cantharidin or placebo, with or without occlusion. The primary outcome was complete lesion clearance. Secondary outcomes included post-treatment lesion count, adverse events, and side effects. No significant differences between the study arms, including baseline lesion count, were observed. The overall mean (SD) baseline lesion count was 22.2 (12.9). The number of participants achieving total clearance is as follows: 7/23 (30.4%) in the cantharidin only arm, 10/24 (41.7%) in the cantharidin with occlusion arm, 2/25 (8.0%) in the placebo with occlusion arm, and 3/22 (13.6%) in the placebo only arm. Post hoc analysis demonstrated that 17/47 (36.2%) participants in the combined cantharidin arms achieved clearance compared to 5/47 (10.6%) in the placebo arms (P = 0.0065). The mean (SD) lesion count change from baseline was -5.1 (12.2) in the placebo only arm; the mean change (SD) was -17.4 (12.8) in the cantharidin only arm (P = 0.0033) and -15.9 (11.6) in the cantharidin with occlusion arm (P = 0.0101). No serious adverse events or side effects were observed. Topical cantharidin was well-tolerated and associated with the resolution of MC.

The Ring Verruca Plantaris in Cantharidin Use A Case Report.

Verrucae (warts) are the most common viral infections of the skin, affecting 7% to 10% of the general population. Typically caused by human papillomavirus type 1, plantar warts manifest as benign proliferation of the epithelial cells on the feet. It has been cited that up to one-third of nongenital warts become recalcitrant, and biopsy is often required to confirm diagnosis and direct appropriate treatment. These treatments can vary from various types of oral medications, acids, ablative modalities, and injections. In this article, we present a case of a recalcitrant plantar wart that appeared to circumferentially spread from the initial site after first-line treatment and presumed resolution with the product cantharidin. The development of ring warts is a known complication associated with cantharidin use, with little described rationale to the presentation.

Overview of Cantharidin and its Analogues.

BACKGROUND: Cantharidin has been categorized as highly toxicant in Chinese medicine. But cantharidin can efficiently treat different types of diseases, such as molluscum contagiosum. While cantharidin is quite useful, unfortunately, due to its side effects, increasing regulations have limited access to this useful therapeutic option. Cantharidin's toxic effects have caused it to fall into disuse for most legitimate medical purposes. Although cantharidin generates effects and its advantages must be realized. Recently, cancer affects people's life more and more. Because cantharidin can treat some cancers, so solutions must be used to reduce side effects. This review aims to describe some its analogues, several efficient methods to inhibit the side effects of cantharidin and pharmacogenomics of cantharidin. METHODS: We searched for research about cantharidin by entering the database. Then evaluated these papers and analyzed their founding, solution, mechanism, etc., and targeted to screen the papers related to the content of our research, and then sorted them out in accordance with the solution, mechanism research and other content. Finally, these content was unified into a framework. RESULTS: Some cantharidin's analogues were found that they show some similar functions to cantharidin and we found that norcantharidin, acylthiourea derivatives, cantharidinamides, anhydride-modified derivatives and other derivatives have less side effects. The modified cantharidin analogues reduce toxicity in hepatocytes. Cantharidin consists of a six-ring and a five-ring, the moiety of oxygen on the six-ring and the anhydride section exhibit biochemical activity. Protein phosphatases are associated with many cellular processes including apoptosis, cell cycle progression and so on. Cantharidin can cause apoptosis and double-stand breakage of DNA. Cantharidin and norcantharidin can efficiently inhibit the activity of mammalian and plant protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A) in vivo. Cantharidin inhibits PP5 at the nanomolar level with an IC50 value of 600 nM. PP5 can manage the cellular survival, death, proliferation and other some intracellular biological activities in mammals. After cantharidin's treatment, the level of EtPP5 mRNA expression was downregulated. Their also can be used to inhibit the Glutathione S-transferases (GSTs), angiogenesis and the expression of A549 human lung cancer cells, trigger eryptosis and induced bladder cancer cell apoptosis. We found that using Vitamin C and ginsenosides and translating cantharidin into nanoparticles can minimize the cantharidin side effects in the patients. CONCLUSION: Cantharidin can inhibit various tumor cell lines. Cantharidin causes both DNA single- and double- strand breaks and induces apoptosis. Although cantharidin shows some toxicity for human, its anti-cancer effects should be taken seriously. Several viable methods can help solve this problem. The most important pharmacogenomics of cantharidin is that cantharidin can inhibit PPs, because PPs are associated with many cellular processes. This prospect is very broad and needs to continue studying.

Combination radiotherapy and cantharidin inhibits lung cancer growth through altering tumor infiltrating lymphocytes.

This study aimed to detect the effect of combination radiotherapy and cantharidin on lung cancer growth. We found that combination therapy with radiotherapy and cantharidin was more effective in inhibiting the tumor growth than radiotherapy or cantharidin alone. It decreased the percentage of CD4+ Tregs and enhanced the percentage of CD8+ T cells, CD4+ Teff cells when comparing to that of single treatment. Combination therapy promoted a great increase in double producing CD8+ T cells and CD4+ Teff cells in tumor infiltrating lymphocytes. Overexpression of CTLA4 reversed the inhibitory action of combination treatment on cancer growth. Our data suggest that combining radiotherapy and cantharidin may have synergistic effects in driving tumor rejection by increasing T-cell infiltration, proliferation and cytokine production.