Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma
Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.
KEY FINDINGS: In addition, Rab7a overexpression is accompanied by reduced migration capacity. Taken together, the study emphasizes that alterations in lysosomal properties facilitate the malignant phenotype and declares the targeting of lysosomal function as a future therapeutic approach.
BACKGROUND: Lysosomes are central in cell homeostasis and participate in macromolecular degradation, plasma membrane repair, exosome release, cell adhesion/migration, and apoptosis. In cancer, alterations in lysosomal function and spatial distribution may facilitate disease progression.
DETAILS: In this study, authors show enhanced lysosomal activity in malignant melanoma cells compared with that in normal human melanocytes. Most lysosomes show perinuclear location in melanocytes, while they are more dispersed in melanoma, with retained proteolytic activity and low pH also in the peripheral population. Rab7a expression is lower in melanoma cells than in melanocytes, and by increasing Rab7a, lysosomes are relocated to the perinuclear region in melanoma. Exposure to the lysosome-destabilizing drug L-leucyl-L-leucine methyl ester causes higher damage in the perinuclear subset of lysosomes in melanomas, whereas differences in subpopulation susceptibility cannot be found in melanocytes. Interestingly, melanoma cells recruit the endosomal sorting complex required for transport-III core protein CHMP4B, involved in lysosomal membrane repair, rather than initiate lysophagy. However, when the perinuclear lysosomal position is promoted by Rab7a overexpression or kinesore treatment, lysophagy is increased.
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Copyright © The Authors. Published by Elsevier, Inc. on behalf of the Society for Investigative Dermatology. All rights reserved.
Source: Eriksson, I., Vainikka, L., Waster, P., et al. (2023). Lysosomal Function and Intracellular Position Determine the Malignant Phenotype in Malignant Melanoma. Journal of Investigative Dermatology. 2023; 143 (9): 1769-1778. Published: September, 2023. DOI: 10.1016/j.jid.2023.01.036.
FDA Approves Engineered Viral Immunotherapy for Treatment-Resistant Advanced Melanoma
FDA approved Tudriqev, an engineered HSV-1-based viral immunotherapy, for adults with treatment-resistant advanced melanoma. The therapy produced tumor responses in 24.2% of patients with a median response duration of 14.1 months. Ongoing Phase III evaluation will further assess long-term efficacy and safety.
KEY FINDINGS: FDA approval of Tudriqev introduces an engineered viral immunotherapy option for adults with treatment-resistant advanced melanoma. By combining direct tumor destruction with immune activation, this therapeutic approach expands the available immunotherapy landscape for patients with limited options after progression on standard treatments. Continued evaluation through confirmatory studies will determine its long-term clinical role in melanoma management.
BACKGROUND: Patients with advanced melanoma whose disease progresses despite available systemic therapies have limited treatment options and significant unmet clinical needs. The U.S. Food and Drug Administration (FDA) approved a new engineered viral immunotherapy designed to provide a treatment option for adults with advanced melanoma that is resistant to prior therapies.
DETAILS: The FDA approved Tudriqev (vusolimogene oderparepvec, formerly RP1), an engineered oncolytic viral immunotherapy developed by Replimune, for adults with unresectable or metastatic melanoma that has progressed following treatment with an anti–PD-1 therapy and, when appropriate, targeted therapy for BRAF-mutated disease. Tudriqev is an engineered herpes simplex virus type 1 (HSV-1)-based therapy administered through intratumoral injection. The treatment is designed to selectively replicate within tumor cells, promote tumor cell destruction, and stimulate an immune response against cancer cells. The FDA approval was based on clinical evidence demonstrating tumor responses in patients with advanced melanoma who had limited therapeutic alternatives. The therapy represents an additional immunotherapeutic approach that uses direct tumor targeting combined with immune system activation. In clinical evaluation, Tudriqev demonstrated tumor reduction or elimination in 24.2% of treated patients, with a median duration of response of 14.1 months. The FDA approval provides a new treatment option for patients with advanced melanoma whose disease has become resistant to prior immunotherapy approaches. A confirmatory Phase III study is ongoing to further evaluate the therapy’s clinical benefit and long-term outcomes.
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Nationwide Recall of Cetirizine Hydrochloride Tablets USP 5 mg Due to Potential Ranitidine Cross-Contamination
Four nationwide-distributed lots of Cetirizine Hydrochloride Tablets USP 5 mg are being voluntarily recalled because of potential ranitidine cross-contamination. Patients with ranitidine hypersensitivity may be at risk for severe allergic reactions or anaphylaxis. No recall-related adverse events had been reported.
KEY FINDINGS: Unique Pharmaceutical Laboratories has initiated a voluntary nationwide recall of four lots of Cetirizine Hydrochloride Tablets USP 5 mg because of potential cross-contamination with ranitidine. The affected product was distributed nationwide in 100-count HDPE bottles under the Rising Pharma Holdings Inc. brand. Patients with hypersensitivity to ranitidine ingredients may be at risk for serious reactions, including severe hypersensitivity and life-threatening anaphylaxis. No adverse events related to the recalled product had been reported at the time of the announcement.
The recall was initiated after a pharmacy technician identified a discrepancy while counting tablets during dispensing. A product complaint described red dots and discoloration on some cetirizine tablets. The recalled lots are GY825029, GY825030, GY825031, and GY825032, each with an expiration date of 10/2028 and NDC 16571-401-10.
The manufacturer and distributor are arranging the return of the affected products. Clinicians should consider the recall when evaluating patients who may have received the affected medication and should assess and manage any suspected adverse reactions appropriately.
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Source: Unique Pharmaceutical Laboratories (A Div. of J. B. Chemicals & Pharmaceuticals Ltd.) Issues Voluntary Nationwide Recall of Cetirizine Hydrochloride Tablets USP 5 mg Due to Potential Cross Contamination with Ranitidine. FDA. Published: July 20, 2026.
Fish Oil Supplementation Maintains Efficacy While Improving Tolerability of Low-Dose Isotretinoin in Moderate-to-Severe Acne Vulgaris
In adults with moderate-to-severe acne, 1 g/day fish oil combined with 10 mg/day isotretinoin was noninferior to isotretinoin alone for acne reduction (mean difference -6.0; 95% CI, -16.5 to 4.5) while better preserving skin hydration and limiting triglyceride elevation, suggesting improved treatment tolerability without loss of efficacy.
KEY FINDINGS: In this randomized controlled non-inferiority trial, adding 1 g/day fish oil to 10 mg/day isotretinoin for 3 months produced acne improvement comparable to isotretinoin alone while offering potential safety advantages. Fish oil supplementation preserved skin hydration, as reflected by smaller reductions in corneometer values, and attenuated increases in serum triglycerides during therapy. These findings suggest that fish oil may be a useful adjunct to low-dose isotretinoin by improving treatment tolerability without reducing clinical effectiveness, although longer-term studies are needed to confirm sustained benefits.
BACKGROUND: Oral isotretinoin is an established treatment for moderate-to-severe acne vulgaris, but its use is frequently limited by mucocutaneous adverse effects and metabolic abnormalities, particularly hypertriglyceridemia. Fish oil possesses anti-inflammatory and lipid-lowering properties that may help mitigate these treatment-related toxicities. This study evaluated whether adding fish oil to low-dose isotretinoin preserves therapeutic efficacy while improving safety.
DETAILS: This randomized, double-masked, controlled, non-inferiority trial enrolled 80 participants aged 18-25 years with moderate-to-severe acne (Investigator's Global Assessment [IGA] score >=3). Participants received either 10 mg isotretinoin plus 1 g fish oil daily (n = 40) or 10 mg isotretinoin plus placebo daily (n = 40) for 3 months. Outcomes included changes in acne lesion counts, IGA scores, skin biophysical parameters, mucocutaneous adverse effects, serum triglyceride (TG) concentrations, and liver transaminase levels. Combination therapy with fish oil was noninferior to isotretinoin monotherapy in reducing total acne lesion counts. The between-group mean difference in total acne count reduction was -6.0 (95% CI, -16.5 to 4.5), meeting the predefined non-inferiority criteria. In addition to maintaining comparable clinical efficacy, patients receiving fish oil experienced smaller reductions in corneometer values, indicating better preservation of skin hydration, and smaller increases in serum triglyceride levels compared with placebo. The study therefore demonstrated that fish oil supplementation improved selected safety outcomes without compromising acne treatment efficacy.
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Source: Sungkhasunya, P., Asawanonda, P., Kumtornrut, C.. et al. Efficacy and Safety of Fish Oil Supplementation Combined With Low-Dose Isotretinoin for Moderate-to-Severe Acne Vulgaris: A Randomized Controlled Non-Inferiority Trial. Journal of the American Academy of Dermatology. 2026; 95(2): 416-422. Published: June 22, 2026. DOI: 10.1016/j.jaad.2026.03.001
Promising Drug Candidates and Emerging Therapeutic Strategies Against Candida auris
Emerging therapies for Candida auris extend beyond conventional antifungal agents and include repurposed drugs, novel antifungal compounds, vaccines, antimicrobial peptides, and nanotechnology-based approaches. While further clinical validation is needed, these strategies may help address the growing challenge of multidrug-resistant C. auris infections.
KEY FINDINGS: This review underscores the expanding pipeline of therapeutic strategies targeting Candida auris, ranging from repurposed medications and next-generation antifungal agents to vaccines, antimicrobial peptides, nanoparticle formulations, and innovative environmental control measures. Although no single therapy has emerged as a definitive solution, compounds such as ibrexafungerp (SCY-078), ATI-2307, and fosmanogepix, together with drug repurposing and bioinspired approaches, represent promising avenues for addressing multidrug-resistant C. auris infections. Continued translational research and clinical evaluation remain essential to establish safe and effective treatment options for this increasingly important fungal pathogen.
BACKGROUND: Candida auris has rapidly emerged as a multidrug-resistant fungal pathogen of global concern since its first identification in 2009. The organism is associated with healthcare-associated outbreaks, high transmissibility, frequent misidentification, and severe invasive infections, with reported mortality rates ranging from 35% to 72%. Resistance to currently available antifungal agents further complicates treatment, with approximately 90% of isolates resistant to fluconazole, around 30% resistant to amphotericin B, and fewer than 5% resistant to echinocandins. These challenges have accelerated efforts to identify novel antifungal therapies and alternative treatment strategies.
DETAILS: This publication is a comprehensive narrative review that summarizes advances in antifungal research targeting C. auris over the preceding decade. The authors evaluated emerging therapeutic approaches from a medicinal chemistry perspective, including drug repurposing, combination therapy, novel antifungal agents, natural products, metal-based compounds, nanoparticles, vaccines, antimicrobial peptides, and environmental decontamination strategies. The review also examined chemical and physicochemical characteristics of promising compounds, including lipophilicity and topological polar surface area, to identify structural features that may facilitate future antifungal drug development. The review highlights several promising therapeutic candidates with activity against multidrug-resistant C. auris. Drug repurposing identified multiple agents with antifungal or antibiofilm activity, including sertraline, miltefosine, iodoquinol, octenidine dihydrochloride, taurolidine, and bensulfuron methyl. Miltefosine demonstrated fungicidal and antibiofilm activity, while encapsulation within alginate nanoparticles reduced toxicity and improved survival in an infected Galleria mellonella model. The NDV-3A vaccine generated cross-reactive antibodies against C. auris and protected neutropenic mice, with additive efficacy when combined with micafungin.
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Among novel antifungal agents, SCY-078 (ibrexafungerp), an orally available 1,3-ß-D-glucan synthesis inhibitor, demonstrated potent activity against C. auris, with an MIC90 of 1 mg/L and MIC50 and MIC90 values of 0.5 µg/mL and 1 µg/mL, respectively, across 100 isolates representing the four major clades. More than 150 strains with diverse resistance profiles were subsequently shown to be uniformly susceptible to SCY-078, and the agent remained active against pan-resistant isolates while also exhibiting antibiofilm activity.
Additional investigational therapies also demonstrated encouraging preclinical activity. The arylamidine T-2307 (ATI-2307) exhibited in vitro MIC values ranging from 0.125 to 4 µg/mL and improved survival while reducing kidney fungal burden in murine infection models following 3 mg/kg once-daily subcutaneous treatment. Other experimental approaches included antimicrobial peptides, ceragenins, fluorinated hydrazone derivatives, and novel chemical scaffolds designed to overcome existing resistance mechanisms.
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Source: Billamboz, M., Fatima, Z., Hameed, S., et al. Promising Drug Candidates and New Strategies for Fighting against the Emerging Superbug Candida auris. Microorganisms. 2021; 9(3): 634. Published: March 18, 2021. DOI: 10.3390/microorganisms9030634.
Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks
Findings suggest intensive chemoprophylaxis of 70% or more of residents in response to influenza outbreaks in NHs within the first 2 days is associated with a lower 14-day risk of hospitalization among residents, with additional evidence to support a benefit when 60% or more or 80% or more of residents receive chemoprophylaxis. These findings could strengthen evidence-based recommendations to inform best practices in managing influenza outbreaks in NHs.
KEY FINDINGS: Study results suggest that clinicians should initiate antiviral chemoprophylaxis for at least 70% of eligible NH residents within 2 days of outbreak detection to lower risk of hospitalization.
BACKGROUND: Influenza outbreaks in nursing homes (NHs) pose a substantial threat to older adults, often resulting in morbidity and mortality. The Centers for Disease Control and Prevention (CDC) and the Infectious Diseases Society of America (IDSA) recommend prompt postexposure prophylaxis, also termed chemoprophylaxis or prophylaxis with oseltamivir, for all residents who are not ill to limit influenza spread in NHs. Purpose of the study is to examine whether initiating antiviral chemoprophylaxis for 70% or more of eligible NH residents within 2 days of influenza outbreak detection is associated with lower all-cause mortality and hospitalization at 14 and 30 days.
DETAILS: Retrospective cohort study using a sequential cluster-randomized target trial emulation and randomize-censor-weight approach for influenza outbreaks (September 1, 2018-May 31, 2022) in 12 US NH corporations. Eligibility criteria were age 18 years or older, present on the outbreak-detection day, no antiviral use in the preceding 7 days, no influenza in the past 14 days, and complete baseline data. Residents were followed up until hospitalization or death, an NH discharge to a nonacute-care location, or the end of follow-up. Data were analyzed from February 2023 to January 2026.
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Exposures: Intensive antiviral chemoprophylaxis with oseltamivir (>=70% of eligible residents within 2 days of outbreak detection) or nonintensive antiviral chemoprophylaxis (0% to <70% of eligible residents).
Outcomes were all-cause death and hospitalizations within 14 and 30 days of outbreak detection. Discrete-time hazard models with pooled logistic regression were applied to estimate weighted risks, risk differences (RDs), and risk ratios (RRs).
Among 404 outbreaks in 318 NHs, 35,086 resident-trial observations (29,683 residents; median age 78 [IQR, 68- 86] years; 60% women; 81% White; 76% vaccinated) met eligibility criteria. Intensive oseltamivir prophylaxis was randomized to 17,155 observations; 17,931 were randomized to nonintensive care. At 14 days, intensive prophylaxis vs nonintensive yielded an RD of -0.06% (95% CI, -0.73% to 0.93%) and an RR of 0.96 (95% CI, 0.56-1.57) for death, and an RD of -0.96% (95% CI, -1.78% to -0.19%) and an RR of 0.79 (95% CI, 0.64-0.96) for hospitalization. At 30 days, the hospitalization differences persisted but were less precise and there continued to be no difference in death.
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Source: Silva, J. B. B., Hsieh, H. T., Howe, C. J., et al. Prompt and Intensive Antiviral Chemoprophylaxis in Nursing Home Influenza Outbreaks. JAMA Internal Medicine.. 2026; 186(6): 714-722. Published: June, 2026. DOI: 10.1001/jamainternmed.2026.0401
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