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MelanomaNSCLC (Non-Small Cell Lung Cancer)Other CancersSCC (Squamous Cell Carcinoma)Biological: T3011Combination Product: T3011 + pembrolizumabRecruitingAustraliaUnited States 0NCT04370587Phase 1Phase 2
A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

A Clinical Study of Intratumoral MVR-T3011 (T3011) Given as a Single Agent and in Combination With Intravenous Pembrolizumab in Participants With Advanced or Metastatic Solid Tumors

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Enh17: Unveiling its Role in Melanoma Progression

KEY TAKEAWAYS

  • The study aimed to elucidate the function and mechanism of a pivotal enhancer in melanoma pathogenesis.
  • The results indicated enh17’s oncogenic role in melanoma progression, elucidating regulatory mechanisms for potential prevention and treatment.

In the realm of genetics, enhancers serve as vital elements in regulating gene expression during both developmental stages and disease processes. Anomalies within enhancers can influence cancer susceptibility and trigger the activation of oncogenes, contributing to the onset of diverse malignancies. However, the specific mechanisms governing the action of most enhancers in cancer remain elusive.

Junyou Zhang and the team aimed to investigate the function and mechanism of a pivotal enhancer in melanoma.

The study utilized multi-omics data to pinpoint enhancer enh17’s role in melanoma progression. CRISPR/Cas9 technology was employed to knock out enh17 in the A375 melanoma cell line. RNA-seq, ChIP-seq, and Hi-C data analysis, coupled with luciferase reporter assays, were employed to identify enh17’s potential target gene.

Subsequent functional experiments validated the function of the target gene ETV4. Integration of multi-omics data with CUT&Tag sequencing validated the binding profile of the inferred transcription factor STAT3.

The results revealed that the enhancer, referred to as enh17, exhibited abnormal activation and contributed to melanoma progression. Deletion of enh17 using CRISPR/Cas9 technology suppressed melanoma cell proliferation, migration, and tumor growth in both in vitro and in vivo settings.

Mechanistically, ETV4 emerged as a target gene regulated by enh17, with functional experiments supporting its involvement in cancer-associated traits. Moreover, STAT3 was identified as a transcription factor binding to enh17, orchestrating the transcriptional regulation of ETV4.

The study concluded that enh17 exerts an oncogenic influence, driving tumor progression in melanoma. Additionally, the investigation fully elucidated enh17’s transcriptional regulatory mechanisms, potentially paving the way for innovative approaches in melanoma prevention and treatment.

Funding was provided by the National Natural Science Foundation of China and the Fundamental Research Funds for the Central Universities.

Source: https://pubmed.ncbi.nlm.nih.gov/38849954/

Zhang J, Wang Q, Qi S, et al. (2024). “An oncogenic enhancer promotes melanoma progression via regulating ETV4 expression.” J Transl Med. 2024 Jun 7;22(1):547. doi: 10.1186/s12967-024-05356-8. PMID: 38849954; PMCID: PMC11157841.

Rising Trends in DMM: Insights from Subgroup Analysis

KEY TAKEAWAYS

  • The study aimed to analyze 15-year trends in patients with DMM incidence and mortality.
  • Researchers noticed that DMM’s incidence and incidence-based mortality rates have significantly increased in recent years.

Recent data show a significant increase in the detection and mortality rates of Desmoplastic Malignant Melanoma (DMM), highlighting the urgent need for comprehensive epidemiological analysis to inform precise medical and public health strategies.

Hai Yu and the team aimed to elucidate variations in DMM incidence and mortality over a 15-year period (2005-2019).

They performed an inclusive analysis utilizing data sourced from the Surveillance, Epidemiology, and End Results (SEER) database, specifically focusing on patients with DMM. Incidence and incidence-based mortality rates (IBM) were directly extracted from the SEER database. Joinpoint regression analysis was employed to analyze the data, enabling the calculation of the average annual percent change (AAPC) along with its corresponding 95% confidence interval (CI).

About 3,384 cases of DMM were identified between 2005 and 2019, boasting an age-adjusted incidence rate of 36.3 cases per 1000,000 person-years (95% CI 3.51-3.76) and an IBM of 1.65cases per 1000,000 person-years (95% CI 1.57-1.74). Of these, 2,353 were males (69.53%) and 1,031 were females (30.47%). There were 1894 patients (55.97%) who were over 70 years old. Predominantly, DMM lesions manifested in exposed areas: Limbs (955, 28.22%), Face (906, 26.77%), and Scalp and Neck (865, 25.56%).

The incidence of DMM increased significantly at a rate of APC = 0.9% during 2005-2019, while the incidence-based mortality showed a significant upward trend (APC = 7%) during 2005-2012, and slowly increasing trend (APC = 0.6%) during 2012-2019. In contrast to the modest upward trajectory in female incidence and mortality, male incidence initially surged, later declining, while male mortality peaked and stabilized post-2012. The primary sites for incidence and mortality were chronically sun-exposed areas: Face, Scalp and Neck, and Limbs.

In recent years, there has been a notable rise in both the incidence and incidence-based mortality rates of DMM. Subgroup analyses revealed distinct trends within different demographic groups, underscoring the importance of tailored approaches in understanding and addressing the complexities of DMM.

The study was funded by the Key Scientific Problems and Medical Technical Problems Research Project of China Medical Education Association and Guangdong Provincial Key Laboratory of Traditional Chinese Medicine Informatization.

Source: https://pubmed.ncbi.nlm.nih.gov/38796649/

Yu H, Zhu L, Zhang J, et al. (2024). “Joinpoint regression analysis of recent trends in desmoplastic malignant melanoma incidence and mortality: 15-year multicentre retrospective study.” Arch Dermatol Res. 2024 May 25;316(6):273. doi: 10.1007/s00403-024-02928-y. PMID: 38796649.

UVA-1 Therapy Shows No Rise in Skin Cancer Risk

KEY TAKEAWAYS

  • The study aimed to investigate the carcinogenic risk of medium-dose UVA-1 phototherapy in patients with MM.
  • Researchers noticed that medium-dose UVA-1 phototherapy does not increase skin tumor risk or worsen facial photoaging; further investigation is ongoing.

UVA-1 phototherapy was first used to treat atopic dermatitis and afterwards to several other skin diseases. The contribution of UVA-1 in human photocarcinogenesis, skin photoaging, immune suppression, and hyperpigmentation is now well established. The actual contribution of UVA-1 radiation to the development of malignant melanoma (MM) in humans cannot be excluded.

Davide Cosetti and the team aimed to evaluate the risk of developing skin cancers (non-melanoma skin cancers (NMSCs) and MM) in patients treated with UVA-1 phototherapy with a 5-year dermatological follow-up.

They performed an inclusive analysis in a retrospective cohort study with 31 patients diagnosed with morphea and atopic dermatitis, all of whom were treated with medium-dose UVA-1 phototherapy (34 J/cm2). The study involved annual oncologic prevention visits over a 5-year follow-up period, during which a comprehensive clinical evaluation of the entire skin surface was conducted for each patient.

About 5-year follow-up, a case of basal cell carcinoma (BCC) in the cervical region and 1 case of MM on the back (pT1a) were recorded. In both instances, the patients were female and diagnosed with morphea. The Glogau 3 group was prevalent (42%), consistent with moderate to severe aging, indicating compatibility with the age.

The study concluded that medium-dose UVA-1 phototherapy does not elevate the risk of skin tumors and does not exacerbate facial photoaging. However, the small sample size was the main limitation, precluding statistically significant findings. Individual analysis of daily sun exposure and its correlation with tumor development was also unfeasible.

Further research with larger sample sizes is necessary to validate these findings. Nonetheless, the study underscores the importance of annual dermatological examinations in monitoring patients undergoing this therapy.

No funding information was given.

Source: https://pubmed.ncbi.nlm.nih.gov/38787937/

Cosetti D, Cioppa V, Rubegni P, et qal. (2024). “Carcinogenic risk in patients treated with UVA-1 phototherapy: A 5-year retrospective study.” Photodermatol Photoimmunol Photomed. 2024 May;40(3):e12975. doi: 10.1111/phpp.12975. PMID: 38787937.

Rosemary & Carvacrol Nano Emulsions: New Therapy for Melanoma

Rosemary & Carvacrol Nano Emulsions: New Therapy for Melanoma

KEY TAKEAWAYS

  • The study aimed to evaluate the anticancer effects of two plant extract nano emulsions on human melanoma.
  • The results concluded rosemary and carvacrol nano emulsions could revolutionize local human melanoma therapy.

Marwa Mohamed Ahmed Ellithy and the team aimed to evaluate the anticancer effectiveness of 2 plant extract nano emulsions on human melanoma cell lines.

Following synthesis and characterization, carvacrol and rosemary essential oils were skillfully formulated into nano emulsions. These formulations underwent thorough examination using TEM to precisely determine their charge and size distribution. Subsequently, the A375 human melanoma cell line was meticulously cultured and propagated in a controlled environment.

Upon reaching optimal conditions, the IC50 of the prepared nano emulsions was carefully administered to assess their efficacy. Detailed evaluations were conducted to analyze cell cytotoxicity, angiogenesis effects, and apoptosis induction, providing comprehensive insights into their potential therapeutic applications.

The results revealed that both carvacrol nano emulsion (CNE) and rosemary nano emulsion (RNE) inhibited melanoma cell line viability and angiogenesis while enhancing the expression of the caspase-3 proapoptotic marker.

The study concluded that rosemary and carvacrol extract nano emulsions could serve as revolutionary agents in human melanoma therapy, with potential for local application.

No funding information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/38809638/

Ellithy MMA, Abdrabo RAM. (2024). “Plant Based Extract Oil-Based Nano emulsions: Impact on Human Melanoma Cell Line.” Asian Pac J Cancer Prev. 2024 May 1;25(5):1663-1671. doi: 10.31557/APJCP.2024.25.5.1663. PMID: 38809638.

Optimizing ICI Treatment: Shorter Nivolumab Duration

KEY TAKEAWAYS

  • The study aimed to evaluate if stopping ICIs early is safe for individuals with unresectable stage III or metastatic melanoma on combination therapy.
  • The primary endpoint was the rate of ongoing response.
  • The results concluded that shorter nivolumab treatment was preferred for patients with favorable tumor responses.

Patients with unresectable stage III or metastatic melanoma, often with poor prognostic factors, commonly receive a combination of immune checkpoint inhibitors (ICIs), specifically ipilimumab and nivolumab. This treatment approach is associated with severe immune-related adverse events (irAEs) in approximately 60% of individuals.

Typically, patients undergo ICI therapy for up to 2 years or until disease progression or unacceptable adverse events occur. The incidence of irAEs tends to rise with prolonged treatment duration. Despite observing enduring tumor responses following early treatment discontinuation, consensus on the optimal treatment duration remains elusive.

J C Janssen and the team aimed to assess the safety of early discontinuation of ICIs in individuals with unresectable stage III or metastatic melanoma receiving combination therapy.

The Safe Stop IPI-NIVO trial is a nationwide, multicenter, prospective, single-arm, interventional study conducted in the Netherlands. It aims to include 80 patients with unresectable stage III or metastatic melanoma who are undergoing combination therapy with ipilimumab-nivolumab and have achieved a complete or partial response (CR/PR) according to RECIST v1.1. These patients will be enrolled to undergo early discontinuation of maintenance therapy with anti-PD-1.

The primary endpoint was the rate of ongoing response at 12 months after the initiation of ICI treatment. Secondary endpoints were ongoing response at 24 months, disease control at various time points, melanoma-specific and overall survival, the incidence of immune-related adverse events (irAEs), and health-related quality of life.

From medical, healthcare, and economic viewpoints, avoiding overtreatment is paramount, favoring shorter ICI durations if safe, especially for individuals with favorable tumor responses.

The trial was sponsored by the Erasmus Medical Center.

Source: https://pubmed.ncbi.nlm.nih.gov/38783238/

Clinical Trial: https://clinicaltrials.gov/study/NCT05652673

Janssen JC, van Dijk B, de Joode K, et al. (2024). “Safe Stop IPI-NIVO trial: early discontinuation of nivolumab upon achieving a complete or partial response in patients with irresectable stage III or metastatic melanoma treated with first-line ipilimumab-nivolumab – study protocol.” BMC Cancer. 2024 May 23;24(1):632. doi: 10.1186/s12885-024-12336-0. PMID: 38783238.

PCD-Related Genes as Prognostic Biomarkers in SKCM

KEY TAKEAWAYS

  • The study aimed to investigate the prognostic significance of PCD pathways in SKCM for personalized treatment strategies.
  • The analysis showed CDI’s prognostic value in SKCM, indicating potential for personalized treatment and improved outcomes.

Programmed cell death (PCD) pathways are crucial in skin cutaneous melanoma (SKCM) pathogenesis. Understanding their prognostic significance and clinical implications is essential for developing personalized treatment strategies.

Xiaoxia Wu and the team aimed to investigate the prognostic significance of PCD pathways in people with SKCM to inform personalized treatment strategies.

Using data from The Cancer Genome Atlas (TCGA)-SKCM cohort (n=353), about 1,466 PCD-related genes were analyzed. Researchers established and validated the prognostic cell death index (CDI) through survival analysis and predictive modeling. They conducted functional enrichment, protein-protein interaction (PPI) analysis, consensus clustering, tumor microenvironment assessment, and drug sensitivity analysis to elucidate the biological and clinical relevance of CDI.

The results revealed that CDI effectively stratified individuals with SKCM into high and low-risk groups, demonstrating significant differences in survival outcomes. CDI showed predictive value for survival at 1, 3, and 5 years. The concordance index (C-index) was 0.794 in the training set and 0.792 and 0.821 in the internal and external validation sets, respectively. The area under the curve (AUC) was above 0.75 in all data sets.

Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. Protein-protein interaction (PPI) analysis identified key molecular modules linked to apoptosis and chemokine signaling. Consensus clustering unveiled three distinct subtypes with notable survival disparities based on CDI expression profiles. Tumor microenvironment assessment highlighted correlations with immune cell infiltration, including M1 macrophages and T cells. Drug sensitivity analysis indicated strong correlations between CDI levels and response to immunotherapy.

The study concluded that the analysis establishes the prognostic significance of PCD-related genes in SKCM. CDI emerges as a promising prognostic biomarker, providing insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to enhance SKCM management and improve outcomes for individuals with the condition.

No funding-related information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/38766879/

Wu X, Chen S, Ji Q, et al. (2024). “Characteristics and significance of programmed cell death-related gene expression signature in skin cutaneous melanoma.” Skin Res Technol. 2024 May;30(5):e13739. doi: 10.1111/srt.13739. PMID: 38766879; PMCID: PMC11103559.

Ferroptosis Model Reveals New Insights for Melanoma Therapy

KEY TAKEAWAYS

  • The study aimed to develop a novel prognostic model assessing FRGs’ role in personalized melanoma treatment.
  • The results suggested a strong ferroptosis-related prognostic model, providing new insights into targeted and immunotherapy for melanoma.

Melanoma is highly malignant and heterogeneous, making it essential to develop a specific prognostic model to improve survival and treatment strategies for individuals with the disease. Recent studies have shown that ferroptosis, an iron-dependent form of programmed cell death, results from the overproduction of lipid peroxidation. Despite this, the clinical significance of ferroptosis-related genes (FRGs) in malignant melanoma remains unknown.

Meng Wu and the team aimed to evaluate the involvement of FRGs in melanoma, aiming to create an innovative prognostic model.

Researchers systematically characterized the genetic alterations and mRNA expression of 73 FRGs in The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) dataset. The results were validated using real-time RT-PCR and Western blotting. Subsequently, a multi-gene feature model was constructed using the TCGA-SKCM cohort.

Based on the feature model, individuals with melanoma were classified into high-risk and low-risk groups. Finally, correlations between ferroptosis-related signatures and immune features, immunotherapy efficacy, and drug response were analyzed.

A prognostic model associated with FRGs, developed using the LASSO Cox regression method, identified 13 FRGs correlated with overall survival prognosis in individuals and was validated with external datasets. Subsequently, functional enrichment and immune response analysis indicated notable differences in immune cell infiltration, mutation burden, and hypoxia status between the high-risk and low-risk groups. Additionally, the model proved effective in predicting responses to immunotherapy and drug sensitivity.

The study concluded that a robust ferroptosis-related prognostic signature model was developed, offering potential new insights into targeted therapy and immunotherapy for patients with melanoma.

No funding-related information was available.

Source: https://pubmed.ncbi.nlm.nih.gov/38755712/

Wu M, Li K, Liao Y, et al. (2024). “Multi-omics analysis for ferroptosis-related genes as prognostic factors in cutaneous melanoma.” Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2024 Feb 28;49(2):159-174. doi: 10.11817/j.issn.1672-7347.2024.230401. PMID: 38755712; PMCID: PMC11103070.

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