Article
Oncology
Reinhard Dummer, Georgina V. Long, Caroline Robert, Hussein A. Tawbi, Keith T. Flaherty, Paolo A. Ascierto, Paul D. Nathan, Piotr Rutkowski, Oleg Leonov, Caroline Dutriaux, Mario Mandala, Paul Lorigan, Pier Francesco Ferrucci, Jean Jacques Grob, Nicolas Meyer, Helen Gogas, Daniil Stroyakovskiy, Ana Arance, Jan C. Brase, Steven Green, Tomas Haas, Aisha Masood, Eduard Gasal, Antoni Ribas, Dirk Schadendorf
Summary: The COMBI-i trial evaluated the combination of spartalizumab with dabrafenib and trametinib in patients with BRAF V600-mutant unresectable or metastatic melanoma. The study did not meet its primary end point of progression-free survival, indicating that broad first-line use of this combination is not supported by the results. Further research is needed to identify patient subpopulations who may benefit from checkpoint inhibitor plus targeted therapy combinations.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Hussein A. Tawbi, Caroline Robert, Jan C. Brase, Daniel Gusenleitner, Eduard Gasal, James Garrett, Alexander Savchenko, Gullu Gorgun, Keith T. Flaherty, Antoni Ribas, Reinhard Dummer, Dirk Schadendorf, Georgina Long, Paul D. Nathan, Paolo A. Ascierto
Summary: This study provides important information on drug treatment for melanoma, particularly for potential target subgroups with spartalizumab plus dabrafenib and trametinib therapy. These results have significant implications for future clinical decision-making and personalized treatment.
JOURNAL FOR IMMUNOTHERAPY OF CANCER
(2022)
Article
Oncology
Mariusz L. Hartman, Paulina Koziej, Katarzyna Kluszczynska, Malgorzata Czyz
Summary: Skin melanoma can be cured by surgery at an early stage, but acquired drug resistance is common in advanced melanoma patients. Melanoma cells have an extraordinary ability to adapt to changes in the microenvironment, including drug withdrawal and rechallenge. Changes in protein levels can impact the response of melanoma cells to inhibitors, highlighting the need for a more detailed understanding of drug resistance and patient stratification for novel treatment strategies.
Article
Oncology
Alexander Schulz, Jennifer Raetz, Paula C. Karitzky, Lisa Dinter, Julia K. Tietze, Isabell Kolbe, Theresa Kaeubler, Bertold Renner, Stefan Beissert, Friedegund Meier, Dana Westphal
Summary: In the past, metastatic melanoma was often considered incurable, but with the introduction of new therapies, such as BRAF and MEK inhibitors, significant progress has been made in the treatment of this disease. This study compared different combinations of BRAF and MEK inhibitors, with encorafenib/trametinib showing the highest anti-tumor activity in both BRAF- and NRAS-mutated melanoma cells. These findings suggest that this particular combination may be more effective than current standard treatments and warrants further investigation in clinical trials to potentially improve overall responses in melanoma patients.
Article
Environmental Sciences
Yu-Jen Chiu, Jai-Sing Yang, Fuu-Jen Tsai, Hong-Yi Chiu, Yu-Ning Juan, Yu-Hsiang Lo, Jo-Hua Chiang
Summary: This study identified the resistance of melanoma to vemurafenib and revealed that curcumin can induce apoptosis in vemurafenib-resistant melanoma cells by regulating the EGFR signaling pathway, suggesting curcumin as a potential therapeutic candidate for vemurafenib-resistant melanoma treatment.
ENVIRONMENTAL TOXICOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Paulina Koziej, Katarzyna Kluszczynska, Mariusz L. L. Hartman, Malgorzata Czyz
Summary: Despite advances in targeted therapies for metastatic melanoma, acquired resistance remains a challenge. This study focused on melanoma cells resistant to trametinib, finding that withdrawal and rechallenge of the drug resulted in phenotype switching and adaptation rather than cell death. The study suggests that the phenotype of resistant melanomas might determine the selection of second-line therapy for melanoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Oncology
James S. Wilmott, Hussein Tawbi, Johnathan A. Engh, Nduka M. Amankulor, Brindha Shivalingam, Hiya Banerjee, Ismael A. Vergara, Hansol Lee, Peter A. Johansson, Peter M. Ferguson, Philippe Saiag, Caroline Robert, Jean -Jacques Grob, Lisa H. Butterfied, Richard A. Scolyer, John M. Kirkwood, Georgina V. Long, Michael A. Davies
Summary: The purpose of this study was to identify baseline clinical features associated with outcomes of V600 BRAF-mutant metastatic melanoma patients with melanoma brain metastases (MBM) treated with dabrafenib and trametinib. Exploratory biomarker analysis was also conducted to identify molecular and immunologic changes associated with dabrafenib in MBMs and extracranial metastases (ECM). The results showed that baseline corticosteroid treatment was associated with reduced intracranial response rate (ICRR) and progression-free survival (PFS). These findings highlight the importance of considering corticosteroid treatment in the management of MBM patients and clinical trial design.
CLINICAL CANCER RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
Shujun Han, Mo Zhang, Xiaoyan Qu, Zihao Wu, Zongguan Huang, Yiming Hu, Ying Li, Lanlan Cui, Lu Si, Jiankang Liu, Yongping Shao
Summary: This study identifies a signaling pathway involving SOX10low/TGF-beta/LAMB3/FAK/MMPs that determines the migration and invasion properties of MAPKi-resistant melanoma cells. The LAMB3-Integrinα 3/α 6 signaling mediates the motile and invasive phenotype of resistant cells. SOX10 deficiency in MAPKi-resistant melanoma cells drives LAMB3 upregulation through TGF-beta signaling, and the pro-invasiveness effect of LAMB3 is mediated by the FAK/MMPs axis.
Article
Biochemistry & Molecular Biology
Nelly Durand, Meline Simsir, Laurie Signetti, Fabien Labbal, Robert Ballotti, Isabelle Mus-Veteau
Summary: The study demonstrated that methiothepin enhances the cytotoxicity of doxorubicin on melanoma cells and overcomes resistance of BRAF(V600E) melanoma cells to vemurafenib and trametinib treatment. This highlights the potential of Ptch1 drug efflux inhibition in improving the effectiveness of anti-cancer treatments for melanoma.
Article
Oncology
Carlotta Guzzetti, Cristina Corno, Elisabetta Vergani, Luca Mirra, Emilio Ciusani, Monica Rodolfo, Paola Perego, Giovanni L. Beretta
Summary: KiSS1, a metastasis suppressor, plays an important role in the development and puberty of melanoma cells. This study found that kisspeptin 54, a cleavage product of KiSS1, can enhance the pro-apoptotic activity of vemurafenib in melanoma cells, including drug-resistant cells. These findings suggest the potential of using KiSS1 to modulate apoptotic response.
FRONTIERS IN ONCOLOGY
(2023)
Article
Oncology
Serena Stamatakos, Giovanni Luca Beretta, Elisabetta Vergani, Matteo Dugo, Cristina Corno, Elisabetta Corna, Stella Tinelli, Simona Frigerio, Emilio Ciusani, Monica Rodolfo, Paola Perego, Laura Gatti
Summary: The study found that targeting FASN in melanoma cells resistant to BRAF inhibitors increased sensitivity to the drug, while also activating compensatory pathways. Metabolic changes promoting cell survival are involved in melanoma progression and drug resistance. FASN plays a role in BRAF-mutant melanoma progression, offering new therapeutic opportunities for treatment.
Article
Dermatology
Franziska Noelle Harbers, Beatrice Thier, Simone Stupia, Si Zhu, Marion Schwamborn, Vicky Peller, Heike Chauvistre, Pietro Crivello, Katharina Fleischhauer, Alexander Roesch, Antje Sucker, Dirk Schadendorf, Yong Chen, Annette Paschen, Fang Zhao
Summary: Research found that the state transition of melanoma cells can profoundly affect the function of CD8+ tumor infiltrating lymphocytes, thereby impacting T cell responses to tumors. Melanoma cells undergoing hyperdifferentiation trajectory continuously increased sensitivity to tumor-reactive CD8+ T cells, while those in the dedifferentiation trajectory developed T cell resistance partly due to loss of differentiation antigens.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2021)
Article
Pharmacology & Pharmacy
Hongmei Cui, Qinghui Wang, Duane D. Miller, Wei Li
Summary: This study found that the combination of VERU-111 and Vem has a significant effect on Vem-resistant melanoma, involving molecular signaling pathways such as ERK/AKT and Skp2. This treatment combination holds promise for overcoming Vem resistance in melanoma patients with BRAF (V600E) mutation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell Biology
Ting Wu, Chengyun Li, Changlong Zhou, Xiaxia Niu, Gege Li, Yali Zhou, Xinsheng Gu, Hongmei Cui
Summary: In this study, repression of USP14 sensitized vemurafenib resistance in melanoma through stabilizing Skp2 and blocking its ubiquitination. The combination of Skp2 inhibitor and USP14/UCHL5 inhibitor significantly inhibited cell proliferation, migration, invasion, and colony formation in vemurafenib-sensitive and vemurafenib-resistant melanoma. The dual treatment also led to enhanced apoptosis and autophagy in melanoma cells.
CELL BIOLOGY AND TOXICOLOGY
(2023)
Article
Oncology
Michael B. Atkins, Sandra J. Lee, Bartosz Chmielowski, Ahmad A. Tarhini, Gary I. Cohen, Thach-Giao Truong, Helen H. Moon, Diwakar Davar, Mark O'Rourke, Joseph J. Stephenson, Brendan D. Curti, Walter J. Urba, Joanna M. Brell, Pauline Funchain, Kari L. Kendra, Alexandra P. Ikeguchi, Anthony Jaslowski, Charles L. Bane, Mark A. Taylor, Madhuri Bajaj, Robert M. Conry, Robert J. Ellis, Theodore F. Logan, Noel Laudi, Jeffrey A. Sosman, David G. Crockett, Andrew L. Pecora, Ian J. Okazaki, Sowjanya Reganti, Sunandana Chandra, Samantha Guild, Helen X. Chen, Howard Z. Streicher, Jedd D. Wolchok, Antoni Ribas, John M. Kirkwood
Summary: Combination programmed cell death protein 1/cytotoxic T-cell lymphocyte-4-blockade and dual BRAF/MEK inhibition have shown significant clinical benefit in patients with BRAFV600-mutant metastatic melanoma. This study aimed to determine the best initial treatment or treatment sequence in this population.
JOURNAL OF CLINICAL ONCOLOGY
(2023)
Article
Obstetrics & Gynecology
Maria Szubert, Magdalena Rogut, Magdalena Zietara, Tomasz Wierzbowski, Jacek Wilczynski, Malgorzata Czyz
Summary: This study aimed to identify novel biomarkers for peritoneal endometriosis by evaluating the mRNA expression of specific genes in endometrial tissue. Results showed that NGF mRNA expression was decreased in women with endometriosis, suggesting a potential role in early diagnosis. Further evaluation of changes in NGF expression in eutopic endometrium of patients with peritoneal endometriosis is warranted.
JOURNAL OF GYNECOLOGY OBSTETRICS AND HUMAN REPRODUCTION
(2021)
Article
Oncology
Mariusz L. Hartman, Anna Gajos-Michniewicz, Julita A. Talaj, Aleksandra Mielczarek-Lewandowska, Malgorzata Czyz
Summary: Targeting therapies for BRAF(V600) and MEK1/2 rarely have lasting effects in melanoma patients. By studying BRAF(V600E) melanoma cell lines, it was found that encorafenib can modulate the balance of apoptosis-regulating proteins, predict induction of apoptosis, and demonstrate that MCL-1 is a druggable target to potentiate encorafenib activity.
Article
Biochemistry & Molecular Biology
Ewelina Madej, Damian Ryszawy, Anna A. Brozyna, Malgorzata Czyz, Jaroslaw Czyz, Agnieszka Wolnicka-Glubisz
Summary: RIPK4 expression in melanoma is heterogeneous, with higher levels in metastatic melanoma cell lines. Down-regulating RIPK4 reduces invasive potential and pro-invasive protein levels, while PMA treatment leads to RIPK4 degradation and cell migration control via NF-kappa B signaling in a RIPK4-dependent or independent manner depending on cell origin and phenotype.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Oncology
Michal Wozniak, Malgorzata Czyz
Summary: Long non-coding RNAs (lncRNAs) are heterogeneous RNA molecules that can regulate crucial cellular processes through diverse mechanisms, and their aberrant expression may lead to the development of cancers such as melanoma. Therefore, lncRNAs have the potential to be promising biomarkers for the diagnosis of melanoma.
Article
Biochemistry & Molecular Biology
Joanna Bojarska, Martin Breza, Milan Remko, Malgorzata Czyz, Anna Gajos-Michniewicz, Michal Zimecki, Krzysztof Kaczmarek, Izabela D. Madura, Jakub M. Wojciechowski, Wojciech M. Wolf
Summary: Short cyclic peptides have been found to have cytotoxic and cytostatic effects on melanoma cells. Among them, CLA is the most active peptide that can significantly reduce the viability of melanoma cells. Cyclic peptides exhibit better biological activity compared to their linear counterparts. The crystal structure of cyclic tetrapeptide 4B8M, a close analog of P11, has been reported for the first time, providing important insights for drug discovery.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Katarzyna Kluszczynska, Malgorzata Czyz
Summary: Extracellular vesicles (EVs) play an important role in cell-to-cell communication, carrying functional biomolecules that influence melanoma development and immune evasion. They are involved in various steps of melanoma progression and can contribute to resistance to immunotherapy and targeted therapy. Furthermore, EVs have potential applications in melanoma diagnostics and therapy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Biochemistry & Molecular Biology
Mariusz L. Hartman, Malgorzata Czyz
Summary: Proteins from the BCL-2 family play critical roles in cell survival, apoptosis, and other cellular processes. BCL-G, an atypical member of this family, has been found to have unique functions and complex regulatory mechanisms. Although it is predominantly expressed in normal testes and the gastrointestinal tract, genetic alterations of the BCL2L14 gene have been observed in various types of cancer. In addition to its known involvement in apoptosis, recent studies have revealed novel apoptosis-unrelated functions of BCL-G in intracellular trafficking, immunomodulation, and regulation of the mucin scaffolding network.
CELL DEATH AND DIFFERENTIATION
(2023)
Article
Biochemistry & Molecular Biology
Paulina Koziej, Katarzyna Kluszczynska, Mariusz L. L. Hartman, Malgorzata Czyz
Summary: Despite advances in targeted therapies for metastatic melanoma, acquired resistance remains a challenge. This study focused on melanoma cells resistant to trametinib, finding that withdrawal and rechallenge of the drug resulted in phenotype switching and adaptation rather than cell death. The study suggests that the phenotype of resistant melanomas might determine the selection of second-line therapy for melanoma patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Genetics & Heredity
Malgorzata Drzewiecka, Anna Gajos-Michniewicz, Grazyna Hoser, Dominika Jasniak, Gabriela Barszczewska-Pietraszek, Przemyslaw Sitarek, Piotr Czarny, Janusz Piekarski, Maciej Radek, Malgorzata Czyz, Tomasz Skorski, Tomasz Sliwinski
Summary: Inhibition of HDACs shows potential as an anti-cancer therapy due to its disruption of acetylation in cancer cells. This study demonstrates that the combination of HDAC inhibitors, alkylating agents, and PARP inhibitors enhances the treatment of melanoma by increasing DNA double strand breaks and reducing cell survival. The findings suggest that HDACs play a role in melanoma cell resistance to methylating agent-based therapies.
Article
Oncology
Mariusz L. Hartman, Paulina Koziej, Katarzyna Kluszczynska, Malgorzata Czyz
Summary: Skin melanoma can be cured by surgery at an early stage, but acquired drug resistance is common in advanced melanoma patients. Melanoma cells have an extraordinary ability to adapt to changes in the microenvironment, including drug withdrawal and rechallenge. Changes in protein levels can impact the response of melanoma cells to inhibitors, highlighting the need for a more detailed understanding of drug resistance and patient stratification for novel treatment strategies.
