Petra Nikolett Péter

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Safety and Efficacy Analysis of Targeted and Immune Combination Therapy in Advanced Melanoma—A Systematic Review and Network Meta-Analysis

International Journal of Molecular Sciences (2024)

A Lengyel Fanni Adél Meznerics Noémi Ágnes Galajda Noémi Gede Tamás Kói

The combinations of BRAF inhibitor-based targeted therapies with immune checkpoint inhibitors currently represent less common therapeutic approaches in advanced melanoma. The aim of this study was to assess the safety and efficacy of currently available melanoma treatments by conducting a systematic review and network meta-analysis. Four databases were systematically searched for randomized clinical studies that included patients with advanced/metastatic melanoma receiving chemotherapy, immune checkpoint inhibitors, BRAF/MEK inhibitor therapy, or combinations thereof. The primary endpoints were treatment-related adverse events (TRAE), serious adverse events (SAE) of grade ≥ 3 adverse events, therapy discontinuation, progression-free survival (PFS), as well as objective response rate (ORR) and complete response rate (CRR). A total of 63 articles were eligible for our systematic review; 59 of them were included in the statistical analysis. A separate subgroup analysis was conducted to evaluate the efficacy outcomes, specifically in BRAF-positive patients. Triple combination therapy or triple therapy (inhibiting BRAF, MEK and PD1/PDL1 axis) showed significantly longer progression-free survival compared to BRAF + MEK combination therapies (HR = 0.76; 95% CI 0.64-0.9), but similar objective and complete response rates in BRAF-mutated melanoma. This safety analysis suggests that triple therapy is not inferior to combined immune checkpoint inhibitors (ICI) and BRAF/MEK therapies in terms of serious adverse events and therapy discontinuation rates. However, monotherapies and BRAF/MEK combinations showed notable advantage over triple therapy in terms of treatment-related adverse events. Combination strategies including BRAF/MEK-targeted therapies with ICI therapies are effective first-line options for advanced, BRAF-mutant melanoma; however, they are associated with more frequent side effects. Therefore, future RCTs are required to evaluate and identify high-risk subpopulations where triple therapy therapies should be considered.

Targeted Therapy

10.3390/ijms252312821

Cite

Citations (0)

Unbiased Drug Target Prediction Reveals Sensitivity to Ferroptosis Inducers, HDAC and RTK Inhibitors in Melanoma Subtypes

International Journal of Dermatology (2024)

Indira Plá Botond L. Szabolcs Petra Nikolett Péter Zsuzsanna Újfaludi Yonghyo Kim

The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem.

Druggability

Targeted Therapy

10.1111/ijd.17586

Cite

Citations (0)

Identifying Ferroptosis Inducers, HDAC, and RTK Inhibitor Sensitivity in Melanoma Subtypes through Unbiased Drug Target Prediction

bioRxiv (Cold Spring Harbor Laboratory) (2024)

Indira Plá Botond L. Szabolcs Petra Nikolett Péter Zsuzsanna Újfaludi Yonghyo Kim

Abstract The utilization of PD1 and CTLA4 inhibitors has revolutionized the treatment of malignant melanoma (MM). However, resistance to targeted and immune-checkpoint-based therapies still poses a significant problem. Here we mine large scale MM proteogenomic data integrating it with MM cell line dependency screen, and drug sensitivity data to identify druggable targets and forecast treatment efficacy and resistance. Leveraging protein profiles from established MM subtypes and molecular structures of 82 cancer treatment drugs, we identified nine candidate hub proteins, mTOR, FYN, PIK3CB, EGFR, MAPK3, MAP4K1, MAP2K1, SRC and AKT1, across five distinct MM subtypes. These proteins serve as potential drug targets applicable to one or multiple MM subtypes. By analyzing transcriptomic data from 48 publicly accessible melanoma cell lines sourced from Achilles and CRISPR dependency screens, we forecasted 162 potentially targetable genes. We also identified genetic resistance in 260 genes across at least one melanoma subtype. In addition, we employed publicly available compound sensitivity data (Cancer Therapeutics Response Portal, CTRPv2) on the cell lines to assess the correlation of compound effectiveness within each subtype. We have identified 20 compounds exhibiting potential drug impact in at least one melanoma subtype. Remarkably, employing this unbiased approach, we have uncovered compounds targeting ferroptosis, that demonstrate a striking 30x fold difference in sensitivity among different subtypes. This implies that the proteogenomic classification of melanoma has the potential to predict sensitivity to ferroptosis compounds. Our results suggest innovative and novel therapeutic strategies by stratifying melanoma samples through proteomic profiling, offering a spectrum of novel therapeutic interventions and prospects for combination therapy. Highlights (1) Proteogenomic subtype classification can define the landscape of genetic dependencies in melanoma (2) Nine proteins from molecular subtypes were identified as potential drug targets for specified MM patients (3) 20 compounds identified that show potential effectiveness in at least one melanoma subtype (4) Proteogenomics can predict specific ferroptosis inducers, HDAC, and RTK Inhibitor sensitivity in melanoma subtypes Graphical abstract

Druggability

10.1101/2024.02.08.579424

Cite

Citations (0)

401 Genetic dependency and compound sensitivity mapping of melanoma subtypes based on proteogenomic profiling

Journal of Investigative Dermatology (2024)

B. Szabolcs Indira Plá Petra Nikolett Péter Young-Wook Kim Péter Horvatovich

Profiling (computer programming)

10.1016/j.jid.2024.10.411

Cite

Citations (0)

Efficacy and Safety of Triple Therapy in Advanced Melanoma — a Systematic Review and Network Meta-Analysis

A Lengyel Lajos Kemény Fanni Adél Meznerics Noémi Ágnes Galajda Noémi Gede

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Copy DOI

10.2139/ssrn.4765230

Cite

Citations (1)

Examination of the relationship between pigmentation, UV addiction and vitamin D

Bőrgyógyászati és Venerológiai Szemle (2024)

Benedek Nagy Petra Nikolett Péter Zsófia Erzsébet Csábi Anna A. Ascsillán Lajos V. Kemény

In the following paper, the Authors aim to describe the complex relationship between pigmentation, UV addiction and vitamin D and their evolutionary connections based on recent advances in research. It has been long suggested that prolonged UV exposure can induce addiction and a dependence-like state in some individuals, with β-endorphin released from keratinocytes in response to UV. An evolutionary benefit of UV addiction may be the promotion of vitamin D synthesis following chronic UV exposure. Vitamin D synthesis was also an evolutionary driver of the lighter skin in the Northern Hemisphere, so presumably the UV-induced addictive pleasant sensation may have once similarly facilitated the maximisation of vitamin D synthesis by increasing time spent under the sun. However, excessive UV exposure increases the risk of many skin cancers, so it is important to better understand vitamin D, pigmentation and the pleasurable effects that follow UV radiation.

10.7188/bvsz.2024.100.3.1

Cite

Citations (0)