The DOI matches its Crossref record; 243 of the 243 references it cites were found in a registry or an index.
Cell-state dynamics and therapeutic resistance in melanoma from the perspective of MITF and IFNγ pathways
Open accessAbstract
Targeted therapy and immunotherapy have greatly improved the prognosis of patients with metastatic melanoma, but resistance to these therapeutic modalities limits the percentage of patients with long-lasting responses. Accumulating evidence indicates that a persisting subpopulation of melanoma cells contributes to resistance to targeted therapy or immunotherapy, even in patients who initially have a therapeutic response; however, the root mechanism of resistance remains elusive. To address this problem, we propose a new model, in which dynamic fluctuations of protein expression at the single-cell level and longitudinal reshaping of the cellular state at the cell-population level explain the whole process of therapeutic resistance development. Conceptually, we focused on two different pivotal signalling pathways (mediated by microphthalmia-associated transcription factor (MITF) and IFNγ) to construct the evolving trajectories of melanoma and described each of the cell states. Accordingly, the development of therapeutic resistance could be divided into three main phases: early survival of cell populations, reversal of senescence, and the establishment of new homeostatic states and development of irreversible resistance. On the basis of existing data, we propose future directions in both translational research and the design of therapeutic strategies that incorporate this emerging understanding of resistance.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“De-differentiation is exemplified by colon carcinogenesis (due to the loss of the differentiation-inducing transcription factor HOXA5 and SMAD4), 141,142 melanomagenesis (due to the loss of the transcription factor MITF), 143 or pancreatic neuroendocrine tumors (due to the loss of a differentiation-inducing miRNA in b cells).144”
From Meta-hallmarks of aging and cancer (2023) · cites this paper as [143]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PD-1 and PD-L1 Immune Checkpoint Blockade to Treat Breast Cancer
Hartkopf, A. D., Taran, F., Wallwiener, M., Walter, C. B., Krämer, B., Grischke, E., & Brucker, S. Y. (2016) · Breast Care · doi:10.1159/000453569 · Cited by 30,989
Siegel, R. L., Miller, K. D., & Jemal, A. (2018) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21442 · Cited by 16,632
Siegel, R. L., Miller, K. D., & Jemal, A. (2016) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21332 · Cited by 16,003
Adverse Renal Effects of Immune Checkpoint Inhibitors: A Narrative Review
Wanchoo, R., Karam, S., Uppal, N. N., Barta, V. S., Deray, G., Devoe, C., Launay‐Vacher, V., Jhaveri, K. D., & on behalf of Cancer and Kidney International Network Workgroup on Immune Checkpoint Inhibitors (2017) · American Journal of Nephrology · doi:10.1159/000455014 · Cited by 15,320
Improved Survival with Ipilimumab in Patients with Metastatic Melanoma
Hodi, F. S., O'Day, S. J., McDermott, D. F., Weber, R. W., Sosman, J. A., Haanen, J. B., Gonzalez, R., Robert, C., Schadendorf, D., Hassel, J. C., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1003466 · Cited by 15,155
Siegel, R. L., Miller, K. D., & Jemal, A. (2017) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.21387 · Cited by 14,712
Siegel, R. L., Miller, K. D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21254 · Cited by 11,854
Mutations of the BRAF gene in human cancer
Davies, H., Bignell, G. R., Cox, C., Stephens, P., Edkins, S., Clegg, S., Teague, J., Woffendin, H., Garnett, M. J., Bottomley, W., et al. (2002) · Nature · doi:10.1038/nature00766 · Cited by 10,674
Stem cells, cancer, and cancer stem cells
Reya, T., Morrison, S. J., Clarke, M. F., & Weissman, I. L. (2001) · Nature · doi:10.1038/35102167 · Cited by 9,738
The Epithelial-Mesenchymal Transition Generates Cells with Properties of Stem Cells
Mani, S. A., Guo, W., Liao, M.-J., Eaton, E. N., Ayyanan, A., Zhou, A. Y., Brooks, M. W., Reinhard, F., Zhang, C. C., Shipitsin, M. V., et al. (2008) · Cell · doi:10.1016/j.cell.2008.03.027 · Cited by 8,839
Cited by
Sorted by citations
Meta-hallmarks of aging and cancer
López-Otín, C., Pietrocola, F., Roiz-Valle, D., Galluzzi, L., & Kroemer, G. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2022.11.001 · Cited by 529
Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunitiesPreprint
Rambow, F., Marine, J., & Goding, C. R. (2019) · Genes & Development · doi:10.1101/gad.329771.119 · Cited by 348
“In a recent review (Bai et al. 2019), it has been proposed that the majority of cells within a melanoma tumor will exist in a continuous spectrum of states rather than fit any specific category and that the outliers will be the most unstable and therefore more likely to revert back to the most common state shared by t…”
BackgroundPre-clinical modeling of cutaneous melanoma
Rebecca, V. W., Somasundaram, R., & Herlyn, M. (2020) · Nature Communications · doi:10.1038/s41467-020-15546-9 · Cited by 244
The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single-Cell Resolution
Nirmal, A. J., Maliga, Z., Vallius, T., Quattrochi, B., Chen, A. A., Jacobson, C. A., Pelletier, R. J., Yapp, C., Arias-Camison, R., Chen, Y., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-1357 · Cited by 211
Principles and mechanisms of non-genetic resistance in cancer
Bell, C. C., & Gilan, O. (2019) · British Journal of Cancer · doi:10.1038/s41416-019-0648-6 · Cited by 190
“Therefore, transient non-genetic resistance might be a common precursor to the eventual formation of stable resistance.(25,38) However, in other instances, when the cancer cell is sufficiently plastic and alternative stable states are accessible, these compensatory changes could drive the cell directly into another st…”
BackgroundAdaptive redox homeostasis in cutaneous melanoma
Arslanbaeva, L. R., & Santoro, M. M. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101753 · Cited by 87
“The MITF transcription factor regulates the development of cells from neural crest to melanocytes and is critical for melanomagenesis [44].”
BackgroundGenetic screening for single-cell variability modulators driving therapy resistance
Torre, E. A., Arai, E., Bayatpour, S., Jiang, C., Beck, L. E., Emert, B. L., Shaffer, S. M., Mellis, I. A., Fane, M. E., Alicea, G. M., et al. (2021) · Nature Genetics · doi:10.1038/s41588-020-00749-z · Cited by 71
The Role of PTEN Loss in Immune Escape, Melanoma Prognosis and Therapy Response
Cabrita, R., Mitra, S., Sanna, A., Ekedahl, H., Lövgren, K., Olsson, H. L., Ingvar, C., Isaksson, K., Lauss, M., Carneiro, A., et al. (2020) · Cancers · doi:10.3390/cancers12030742 · Cited by 69
“Such melanoma cells have different molecular properties and respond differently to therapy [9,18].”
BackgroundCellular senescence in ionizing radiation (Review)
Chen, Z., Cao, K., Xia, Y., Li, Y., Hou, Y., Wang, L., Li, L., Chang, L., & Li, W. (2019) · Oncology Reports · doi:10.3892/or.2019.7209 · Cited by 69
Rethinking the biology of metastatic melanoma: a holistic approach
Vandyck, H. H., Hillen, L. M., Bosisio, F. M., van den Oord, J., Hausen, A. Z., & Winnepenninckx, V. J. L. (2021) · Cancer and Metastasis Reviews · doi:10.1007/s10555-021-09960-8 · Cited by 65
“transcriptional states rather than distinct artificial categories [27] (Fig.”
BackgroundWawrzyniak, P., & Hartman, M. L. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02294-x · Cited by 62
“…a state characterized by a low level and activity of MITF, among other factors, has been connected to resistance to available therapies [137], whereas distinct trajectories between the IFN-γ and MITF signaling pathways are closely related to the resistance state of melanoma to immunotherapy [138].”
Liu, S., Jiang, A., Tang, F., Duan, M., & Li, B. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02323-9 · Cited by 60
“MITF-low melanomas recruit myeloid cells to sustain the drug tolerance to BRAF inhibitor and immunotherapy [91–94, 128, 129].”
Immune escape and metastasis mechanisms in melanoma: breaking down the dichotomy
Shirley, C. A., Chhabra, G., Amiri, D., Chang, H., & Ahmad, N. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1336023 · Cited by 54
Single cell analysis to dissect molecular heterogeneity and disease evolution in metastatic melanoma
Fattore, L., Ruggiero, C. F., Liguoro, D., Mancini, R., & Ciliberto, G. (2019) · Cell Death and Disease · doi:10.1038/s41419-019-2048-5 · Cited by 50
Radaszkiewicz, T. W., Nosková, M., Gömöryová, K., Blanářová, O. V., Radaszkiewicz, K. A., Pícková, M., Víchová, R., Gybeľ, T., Kaiser, K., Demková, L., et al. (2021) · eLife · doi:10.7554/elife.65759 · Cited by 45
Gambi, G., Mengus, G., Davidson, G., Demesmaeker, E., Cuomo, A., Bonaldi, T., Katopodi, V., Malouf, G. G., Leucci, E., & Davidson, I. (2022) · Cancer Research · doi:10.1158/0008-5472.can-22-0959 · Cited by 40
Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency
Khaliq, M., & Fallahi‐Sichani, M. (2019) · Cancers · doi:10.3390/cancers11101480 · Cited by 39
“Such heterogeneity could influence the nature and relative strength of the pathways through which each tumor responds or adapts to BRAF and MEK inhibition [126].”
BackgroundHuman TYRP1: Two functions for a single gene?
Gautron, A., Migault, M., Bachelot, L., Corre, S., Galibert, M., & Gilot, D. (2020) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12951 · Cited by 34
Dilenko, H., Tomankova, K. B., Válková, L., Hošíková, B., Kolaříková, M., Malina, L., Bajgar, R., & Kolářová, H. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s461300 · Cited by 38
Targeted and immunotherapies in BRAF mutant melanoma: where we stand and what to expect
Bai, X. L., & Flaherty, K. T. (2020) · British Journal of Dermatology · doi:10.1111/bjd.19394 · Cited by 38
Self-citationLi, D., Ren, J., Li, J., Zhang, Y., Lou, Y., Zhu, J., Liu, P., Chen, Y., Yu, Z., Zhao, L., et al. (2021) · Chemical Engineering Journal · doi:10.1016/j.cej.2021.129557 · Cited by 35
Zhang, L., Yang, J., Chen, G., Xie, Q., Fu, Q.-Y., Xia, H.-F., Li, Y., Huang, J., Li, Y., Wu, M., et al. (2024) · Nature Communications · doi:10.1038/s41467-024-48200-9 · Cited by 35
Najem, A., Soumoy, L., Sabbah, M., Krayem, M., Awada, A. H., Journé, F., & Ghanem, G. (2022) · Cells · doi:10.3390/cells11071157 · Cited by 38
“Cells 2022, 11, 1157 8 of 32 In this context, Bai et al. 2019 [48] recently proposed a model in which the development of resistance to both targeted therapy and immunotherapy in melanoma includes three phases: (1) early survival (including persister cells and innate resistant cells); (2) reversal…”
BackgroundMorinishi, L. S., Kochanowski, K., Levine, R. L., Wu, L. F., & Altschuler, S. J. (2020) · Cell Systems · doi:10.1016/j.cels.2020.06.003 · Cited by 32
Phenotypic Heterogeneity in Tumor Progression, and Its Possible Role in the Onset of Cancer
Deshmukh, S., & Saini, S. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.604528 · Cited by 32
“The hypoactivation of the IFNγ signaling inactivates the immunogenicity of the melanoma cells, whereas the hyperactivation creates a dedifferentiated and invasive phenotype which is a stress-induced persister population (Bai et al., 2019).”
BackgroundZheng, Q., Yang, Q., Zhou, J., Gu, X., Zhou, H., Dong, X., Zhu, H., & Chen, Z. (2021) · Cancer Cell International · doi:10.1186/s12935-021-02033-4 · Cited by 30
“indicated considerable differences in immunotherapy tolerance [31].”
The Promise of Liquid Biopsy to Predict Response to Immunotherapy in Metastatic Melanoma
Fattore, L., Ruggiero, C. F., Liguoro, D., Castaldo, V., Catizone, A., Ciliberto, G., & Mancini, R. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.645069 · Cited by 31
Zhang, C., Smalley, I., Emmons, M. F., Sharma, R., Izumi, V., Messina, J. L., Koomen, J. M., Pasquale, E. B., Forsyth, P. A., & Smalley, K. S. M. (2020) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.08.012 · Cited by 30
“Rather, it is likely that there is cell-state plasticity and that metastases are seeded by minor sub-populations of cells that then revert back to a more drug sensitive/proliferative/less invasive state once established in new organs (Bai et al., 2019, Emmons et al., 2019, Smalley et al., 2019).”
Indini, A., Fiorilla, I., Ponzone, L., Calautti, E., & Audrito, V. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23179985 · Cited by 31
Nongenetic Mechanisms of Drug Resistance in Melanoma
Rebecca, V. W., & Herlyn, M. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033533 · Cited by 26
CRISPR screens identify tumor‐promoting genes conferring melanoma cell plasticity and resistance
Gautron, A., Bachelot, L., Aubry, M., Leclerc, D., Quéméner, A. M., Corre, S., Rambow, F., Paris, A., Tardif, N., Leclair, H. M., et al. (2021) · EMBO Molecular Medicine · doi:10.15252/emmm.202013466 · Cited by 32
“However, a recent publication demonstrated that a long-term BRAFi exposure promotes a dedifferentiation process conferring BRAFi resistance (Tsoi et al, 2018; Bai et al, 2019).”
BackgroundInfluentialTRIM14 regulates melanoma malignancy via PTEN/PI3K/AKT and STAT3 pathways
Chen, J., Huang, L., Jin, Q., & Xiang, D. (2021) · Aging · doi:10.18632/aging.203003 · Cited by 26
“In recent years, targeted therapy and immunotherapy have been proved to improve the prognosis of patients with melanoma, especially metastatic melanoma [4, 5].”
BackgroundMicro RNA Transcriptome Profile in Canine Oral Melanoma
Rahman, M. M., Lai, Y., Husna, A. A., Chen, H., Tanaka, Y., Kawaguchi, H., Miyoshi, N., Nakagawa, T., Fukushima, R., & Miura, N. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20194832 · Cited by 27
“Transcription factors like MITF can play a critical role in melanoma [27,28].”
BackgroundFattore, L., Mancini, R., & Ciliberto, G. (2020) · Cancers · doi:10.3390/cancers12113368 · Cited by 26
“Mechanistically, MITFhigh/PGC1αhigh cells exhibit increased OXPHOS coupled with ROS detoxification capacities enabling them to survive under oxidative stress conditions [61].”
BackgroundInfluentialZhang, J., Liu, H., Zhang, W., Li, Y., Fan, Z., Jiang, H., & Luo, J. (2020) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.615671 · Cited by 26
“Some therapeutic treatments, such as targeted therapy and immunotherapy, have been verified to somewhat improve the prognosis of patients with metastatic melanoma (Bai et al., 2019).”
BackgroundEpigenetic modulation reveals differentiation state specificity of oncogene addiction
Khaliq, M., Manikkam, M., Martínez, E. D., & Fallahi‐Sichani, M. (2021) · Nature Communications · doi:10.1038/s41467-021-21784-2 · Cited by 27
“XS139 (rabbit mAb, clone EP854(2)Y, Abcam, Cat# ab195188, AB_2889151, 1:700), Kdm1a (rabbit mAb, clone C69G12, Cell Signaling Technology, Cat# 2184, AB_2070132, 1:1600), Kdm4a (rabbit mAb, clone C37E5, Cell Signaling Technology, Cat# 5328, AB_10828595, 1:100), Kdm4b (rabbit mAb, clone D7E6, Cell Signaling Technology,…”
BackgroundKatkat, E., Demirci, Y., Heger, G., Karagulle, D., Papatheodorou, I., Brāzma, A., & Özhan, G. (2023) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2023.1297910 · Cited by 24
Sarto, L. E., de Góis, E. P., ANDRADE, G. G. D., ALMEIDA, M. S. D., Freitas, J. T. J., JÚNIOR, A. D. S. R., Franco, L. P., Torres, C., de Almeida, E. T., & Gouvêa, C. M. C. P. (2019) · Anticancer Research · doi:10.21873/anticanres.13884 · Cited by 22
Molecular Basis of BRAF Inhibitor Resistance in Melanoma: A Systematic Review
Cosci, I., Salizzato, V., Fiore, P. D., Pigozzo, J., Guarneri, V., D, S. M. M., Ferlin, A., Mathlouthi, S., Piccin, L., & Garofalo, M. (2025) · Pharmaceuticals · doi:10.3390/ph18081235 · Cited by 26
“Tumor heterogeneity affects the strength of signaling pathways through which each tumor responds and adapts to BRAF and MEKi [48].”
Liu, J., Zheng, R., Zhang, Y., Jia, S., He, Y., & Liu, J. (2023) · Cancers · doi:10.3390/cancers15092640 · Cited by 20
The origin of novel traits in cancer
Frank, S. A., & Yanai, I. (2024) · Trends in cancer · doi:10.1016/j.trecan.2024.07.005 · Cited by 20
“In this case, stochasticity arises by random fl uctuations of cellular TF protein levels, creating nonheritable fl uctuations in cellular state [17,18].”
m6A-Related lncRNAs Are Potential Biomarkers for the Prognosis of Metastatic Skin Cutaneous Melanoma
Huang, S., Lyu, S., Gao, Z., Zha, W., Wang, P., Shan, Y., He, J., & Li, Y. (2021) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2021.687760 · Cited by 18
“Therapies such as neoadjuvant treatment and targeted therapy have been shown to improve the prognosis of metastatic melanoma to some extent (Bai et al., 2019).”
BackgroundCirculating microRNAs as diagnostic biomarkers for melanoma: a systematic review and meta-analysis
Wu, N., Sun, H., Sun, Q., Zhang, F., Ma, L., Hu, Y., & Cong, X. (2023) · BMC Cancer · doi:10.1186/s12885-023-10891-6 · Cited by 18
“Hence, patients with melanoma are prone to missing the opportunity for early diagnosis and treatment [12, 13].”
BackgroundALDH1A3-acetaldehyde metabolism potentiates transcriptional heterogeneity in melanoma
Lu, Y., Trávníčková, J., Badonyi, M., Rambow, F., Coates, A., Khan, Z., Júnior, J. G. M., Murphy, L. C., Garcia-Martinez, P., Marais, R., et al. (2024) · Cell Reports · doi:10.1016/j.celrep.2024.114406 · Cited by 20
Ahmed, F., Tseng, H., Ahn, A., Gunatilake, D., Alavi, S., Eccles, M. R., Rizos, H., Gallagher, S. J., Tiffen, J. C., Hersey, P., et al. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.09.030 · Cited by 18
Lin, H., Wang, L., Chen, H., Shen, Y., Wang, C., Xue, Y., Zheng, Z., Zhang, Y., Xia, D., Wu, Y., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.03.026 · Cited by 17
“Due to the heterogeneous epigenetic and genetic aberrations that accumulate in resistant cells, the persister cell phase seems to be more vulnerable to intervention [3,36].”
Curative-intent pancreas resection for pancreatic metastases: surgical and oncological results
Chikhladze, S., Lederer, A., Kühlbrey, C. M., Hipp, J., Sick, O., Fichtner‐Feigl, S., & Wittel, U. A. (2020) · Clinical & Experimental Metastasis · doi:10.1007/s10585-020-10029-z · Cited by 17
Spoerri, L., Tonnessen-Murray, C. A., Gunasingh, G., Hill, D. S., Beaumont, K. A., Jurek, R. J., Chauhan, J. S., Vanwalleghem, G. C., Fane, M. E., Daignault, S. M., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.09.141747 · Cited by 16
Do innate killing mechanisms activated by inflammasomes have a role in treating melanoma?
Emran, A. A., Tseng, H., Coleman, M. C., Tiffen, J. C., Cook, S. J., McGuire, H. M., Gallagher, S. J., Feng, C. G., & Hersey, P. (2020) · Pigment Cell & Melanoma Research · doi:10.1111/pcmr.12870 · Cited by 14
Shabna, A., Antony, J., Vijayakurup, V., Saikia, M., Liju, V. B., Retnakumari, A. P., Amrutha Nisthul, A., Alex, V. V., Swetha, M., Aiswarya, S. U. D., et al. (2022) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-022-04476-y · Cited by 13
“However, upon advanced melanoma stages where it metastasizes to lymph nodes, alternate strategies, especially immunotherapy, are often recommended [2].”
BackgroundH3K4me3 remodeling induced acquired resistance through O-GlcNAc transferase
Menon, D. R., Hammerlindl, H., Gimenez, G., Hammerlindl, S., Zuegner, E., Torrano, J., Bordag, N., Emran, A. A., Giam, M., Denil, S. L. I. J., et al. (2023) · Drug Resistance Updates · doi:10.1016/j.drup.2023.100993 · Cited by 14
“Evidence is mounting that a cell-intrinsic adaptive response is a major contributor to acquired drug resistance in different cancer types and treatment regimens (Shaffer et al. 2017, Hammerlindl and Schaider, 2018, Bai et al. 2019).”
BackgroundSOX10 , MITF , and microRNAs : Decoding their interplay in regulating melanoma plasticity
Lai, X., Luan, C., Zhang, Z., Wessely, A., Heppt, M. V., Berking, C., & Vera, J. (2025) · International Journal of Cancer · doi:10.1002/ijc.35499 · Cited by 20
“A – 232 There is ongoing debate on melanoma cell states, with some proposing a spectrum of states 233 and others suggesting distinct phenotypes stabilized by FBLs. 234 Our results support the latter, with MITF bistability sustaining specific cell states, as observed in the MITF, BRN2, and miR-211…”
Su, Y., Liu, C., Lu, X., Li, G., Shao, S., Kong, Y., Lee, J. W., Ng, R. H., Wong, S. K., Robert, L., et al. (2019) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/724740 · Cited by 12
“, 2011), recent literature also points to the importance of epigenetic modulations to drugtolerance that can precede the emergence of drug-resistant genotypes in a variety of tumor types (Bai et al., 2019; Hata et al., 2016; Hugo et al., 2015; Pisco et al., 2013; Rambow et al., 2018; Ramirez et al., 2016; Sharma et al…”
BackgroundGhezzi, B., Fiorilla, I., Carreira, Á. S. A., Recco, F., Sorci, L., Avalle, L., Ponzano, A., Mazzola, F., Todesco, A. M., Tommasi, N. D., et al. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02361-2 · Cited by 14
Immune Escape in Prostate Cancer
Reva, B. A., Omelchenko, T., Nair, S. S., & Tewari, A. K. (2020) · Urologic Clinics of North America · doi:10.1016/j.ucl.2020.10.004 · Cited by 11
Harbers, F. N., Thier, B., Stupia, S., Zhu, S., Schwamborn, M., Peller, V., Chauvistré, H., Crivello, P., Fleischhauer, K., Roesch, A., et al. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.03.013 · Cited by 11
LncRNAs in melanoma phenotypic plasticity: emerging targets for promising therapies
Tonin, B. C. B., de Sousa, C.-S. C., John, S. F., & Jasiulionis, M. G. (2024) · RNA Biology · doi:10.1080/15476286.2024.2421672 · Cited by 11
“[23] Bai et al. described a model of targeted therapy and immune checkpoint inhibitor resistance of three phases: early cell survival (innate or induced resistance); senescence reversal; and new homoeostasis, with the establishment of irreversible resistance.”
Malignant melanoma fractional-order mathematical model with stabilized fuzzy sliding mode control
Amilo, D., Sadri, K., & Hınçal, E. (2025) · Computer Methods and Programs in Biomedicine · doi:10.1016/j.cmpb.2025.108912 · Cited by 11
Scales of Cancer Evolution: Selfish Genome or Cooperating Cells?
Brutovský, B. (2022) · Cancers · doi:10.3390/cancers14133253 · Cited by 9
“Phenotypic plasticity enables cancer cells to shift dynamically between a differentiated state with limited tumourigenic potential and an undifferentiated (stem-like) state [68], to escape a targeted therapy by switching to an alternative phenotype [20,70,74,80], to switch between the proliferative and invasive phenot…”
BackgroundXie, Y., Gong, C., Xia, Y. F., Zhou, Y., Ye, T., Mei, T., Chen, H., & Chen, J. (2023) · International Journal of Medical Sciences · doi:10.7150/ijms.80940 · Cited by 9
“It also plays a key role in regulating the senescence, apoptosis, proliferation, and migration of melanoma cells.[18-20] Taken together, the aim of the present study was to evaluate the effects of α-Mangostin on in vivo and in vitro melanoma cells growth, apoptosis, invasion, and migration and determine its synergisti…”
Biology confirmed but biomarkers elusive in melanoma immunotherapy
Luke, J. J., & Ascierto, P. A. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0328-8 · Cited by 8
BRAF V600E ‐PROTAC versus inhibitors in melanoma cells: Deep transcriptomic characterization
Alhassan, S., Elmageed, Z. Y. A., Errami, Y., Wang, G., Abi‐Rached, J., Kandil, E. H., & Zerfaoui, M. (2025) · Clinical and Translational Medicine · doi:10.1002/ctm2.70251 · Cited by 8
Wan, G., Maliga, Z., Yan, B., Vallius, T., Shi, Y., Khattab, S., Chang, C. T., Nirmal, A. J., Yu, K., Liu, D., et al. (2024) · Briefings in Bioinformatics · doi:10.1093/bib/bbae189 · Cited by 8
da Silva, B. A. O., Dias, I. S., Sarto, L. E., de Góis, E. P., Torres, C., de Almeida, E. T., & Gouvêa, C. M. C. P. (2021) · Advanced Pharmaceutical Bulletin · doi:10.34172/apb.2023.017 · Cited by 7
Zhang, Y., Jiang, B., Guo, C., Liu, L., Xu, J., Wang, Y., Shen, C., Zhu, J., Shen, G., Jiang, H., et al. (2021) · Biomaterials Science · doi:10.1039/d1bm00373a · Cited by 7
Modelling EWS::FLI1 protein fluctuations reveal determinants of tumor plasticity in Ewing sarcoma
Suresh, V., Hafemeister, C., Konstantinou, A., Grissenberger, S., Sturtzel, C., Cidre‐Aranaz, F., Wenninger-Weinzierl, A., Zylka, M. M., Queiroz, K. C. S., Kurek, D., et al. (2026) · EMBO Molecular Medicine · doi:10.1038/s44321-025-00364-7 · Cited by 11
“Fluctuations in EF levels may occur stochastically or in response to microenvironmental cues (Apfelbaum et al, 2022a; Bai et al, 2019; Gupta et al, 2011).”
Sun, Y., Zhang, Z., Zhang, K., Liu, Y., Shen, P., Cai, M., Jia, C., Wang, W., Gu, Z., Ma, P., et al. (2021) · PubMed Central · Cited by 6
Momin, M. S. A., Bhadra, J., Bhunia, D., Sannigrahi, A., & De, N. (2025) · Cells · doi:10.3390/cells14120903 · Cited by 6
How cancer arises: Genetics releases, plasticity creates, genetics stabilizes
Frank, S. A. (2025) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2505377122 · Cited by 5
Morel, Á. J. F., Hasanovic, A., Morin, A., Prunier, C., Magnone, V., Lebrigand, K., Aouad, A., Cogoluegnes, S., Favier, J., Pasquier, C., et al. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14050988 · Cited by 5
Zhu, J., Yan, M., Yan, H., Xu, L., Jiang, Z., Liao, G., Zhou, Y., Liu, W., Liang, X., Li, X., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.766852 · Cited by 5
“The absence of interferon-gamma response mediated by the antigen processing machinery in tumor cells may result in their failure to be recognized by the immune system (53, 54).”
BackgroundFane, M. E., Chhabra, Y., Spoerri, L., Simmons, J. L., Ludwig, R., Bonvin, E., Goding, C. R., Sturm, R. A., Boyle, G. M., Haass, N. K., et al. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2020.12.039 · Cited by 5
Reva, B. A., Omelchenko, T., Calinawan, A. P., Nair, S. S., Schadt, E. E., & Tewari, A. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.10.19.345629 · Cited by 5
Spatial determinants of tumor cell dedifferentiation and plasticity in primary cutaneous melanomaPreprint
Vallius, T., Shi, Y., Novikov, E., Pant, S. M., Pelletier, R. J., Chen, Y., Tefft, J. B., Nirmal, A. J., Maliga, Z., Wan, G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.21.660851 · Cited by 8
“…is consistent with the rheostat model of MITF developed from scRNA-Seq data on metastatic tumors and melanoma cell lines; it postulates that MITF has intermediate activity in normal melanocytes, is over-activated in hyperpigmented melanomas cells and is repressed in de-differentiated melanomas 67 .”
Fiorilla, I., Ghezzi, B., Ponzano, A., Moiso, E., Riccardo, F., Tommasi, N., Avalle, L., Carrà, G., Ugolini, F., Calussi, E., et al. (2026) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-026-03734-2 · Cited by 4
Erman, A., Ignjatović, M., Leskovšek, K., Miceska, S., Tratar, U. L., Bošnjak, M., Prevodnik, V. K., Čemažar, M., Sekulović, L. K., Avguštin, G., et al. (2023) · Biomedicines · doi:10.3390/biomedicines11072016 · Cited by 4
Detection of Gene Mutations in Liquid Biopsy of Melanoma Patients: Overview and Future Perspectives
Alrabadi, N., Haddad, R. H., & Alomari, A. K. (2020) · Current Treatment Options in Oncology · doi:10.1007/s11864-020-0708-4 · Cited by 4
Szász, I., Koroknai, V., Patel, V., Hajdú, T., Kiss, T., Ádány, R., & Balázs, M. (2021) · Biomedicines · doi:10.3390/biomedicines9020096 · Cited by 4
“A large number of investigations have focused on identifying the molecular background of resistance, but, regrettably, the leading mechanisms of resistance remain unclear [22].”
BackgroundTranscriptional E2F1/2/3/6 as potential prognostic biomarkers in cutaneous melanoma.
Li, J., Shu, X., Shao, Q., Luo, Q., Diao, Q., Zhang, X., Sui, J.-D., Guo, J., Tao, D., Zhou, X., et al. (2021) · Europe PMC (PubMed Central) · Cited by 4
Monti, M., Picinoli, S., Bozzola, A. M., Ferrari, M., Bugatti, M., Pezzali, I., Carlomagno, M., Carta, G., Orlandi, M., Lora, G., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2025-012222 · Cited by 3
537 Functional melanoma cell heterogeneity is regulated by MITF-dependent cell-matrix interactions
Spoerri, L., Tonnessen-Murray, C. A., Gunasingh, G., Hill, D. S., Beaumont, K. A., Chauhan, J., Smith, A. G., Schaider, H., Gabrielli, B. G., Weninger, W., et al. (2021) · Journal of Investigative Dermatology · doi:10.1016/j.jid.2021.02.563 · Cited by 5
Kim, Y., Kim, D., Park, J., & Chung, Y. (2023) · Experimental Dermatology · doi:10.1111/exd.14900 · Cited by 3
Melanocyte differentiation and epidermal pigmentation is regulated by polarity proteinsPreprint
Knapp, S. K., & Iden, S. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.04.20.051722 · Cited by 3
“Considering the emerging albeit controversial roles of MITF in melanoma formation, progression and therapeutic resistance [4,69,70], our findings also raise new questions about the relevance of Par3/MITF signaling in”
BackgroundSuresh, V., Hafemeister, C., Konstantinou, A., Grissenberger, S., Sturtzel, C., Cidre‐Aranaz, F., Wenninger-Weinzierl, A., Zylka, M. M., Queiroz, K. C. S., Kurek, D., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.04.03.647002 · Cited by 3
“At the cell population level, these fluctuations can lead to diverse phenotypic states and intratumoral heterogeneity (39,40).”
Paun, R. A., Li, L., Mouncef, A., Radzioch, D., & Tabrizian, M. (2025) · Small · doi:10.1002/smll.202409012 · Cited by 5
Ma, Y., Ma, X., Hao, M.-L., Liu, R.-X., Yang, Z., Yang, J., Chen, X., Chen, Y.-N., Zheng, S.-N., Zhang, Y., et al. (2025) · Acta Pharmacologica Sinica · doi:10.1038/s41401-025-01599-3 · Cited by 2
The rise of new targets in melanoma
Bai, X. L., & Flaherty, K. T. (2025) · British Journal of Dermatology · doi:10.1093/bjd/ljaf251 · Cited by 2
Self-citationMETTL10‐Mediated PIAS3 Methylation Links Purine Metabolism to Gastric Cancer Progression
Tan, J., Zhou, H., Ma, J., Zhang, C., Tan, Y., Zhang, B., Zhao, J., Cheng, A., Yang, C., Xu, M., et al. (2025) · Advanced Science · doi:10.1002/advs.202507054 · Cited by 2
LncRNA SNHG12 promotes the malignant progression of melanoma by targeting miR-199b
Xie, Y., & Chen, G. (2022) · Annals of Translational Medicine · doi:10.21037/atm-22-214 · Cited by 2
“The abnormal regulation of a variety of genes and signaling pathways has been associated with the occurrence of melanoma (4).”
A New Approach for Diagnosis of Melanoma from Dermoscopy Images
Deena, G., Bhanu prakash, M., Sreekar, S., & Rohith, S. (2023) · Journal of Survey in Fisheries Sciences · doi:10.53555/sfs.v10i1.920 · Cited by 2
Gautron, A., Bachelot, L., Quéméner, A. M., Corre, S., Aubry, M., Rambow, F., Paris, A., Tardif, N., Leclair, H. M., Coulouarn, C., et al. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.07.08.193102 · Cited by 2
The Spatial Landscape of Progression and Immunoediting in Primary Melanoma at Single Cell ResolutionPreprint
Nirmal, A. J., Maliga, Z., Vallius, T., Quattrochi, B., Chen, A. A., Jacobson, C. A., Pelletier, R. J., Yapp, C., Arias-Camison, R., Chen, Y., et al. (2021) · SSRN Electronic Journal · doi:10.2139/ssrn.3862021 · Cited by 2
Li, M., Du, J., Wang, G., Feng, W., Chen, J., & Zhang, C. (2025) · Discover Oncology · doi:10.1007/s12672-025-02935-z · Cited by 1
“Although targeted therapy and immunotherapy have improved the survival outcome of patients with melanoma, they are not curative for these patients [5].”
Grecea-Balaj, A. M., Şoriţău, O., Brie, I. C., Perde‐Schrepler, M., Virág, P., Fischer‐Fodor, E., Todor, N., Cenariu, M., Nedelea, I., & Ciuleanu, T. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47090746 · Cited by 1
Fragment-based discovery enables direct targeting of the melanoma oncogene MITF
Castelletti, D., Hinrichs, J., Malojčić, G., Ji, F., Desplat, A., Reimer, B., Henry, C., Porter, K. A., Mermet-Meillon, F., Wartmann, M., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-67297-0 · Cited by 1
“Theywouldideallybeorthogonaltoexisting therapies and active across genetic subtypes, in both primary and metastatic melanomas 3 .”
Epigenetic heterogeneity in primary bone cancers
Peneder, P., Tomazou, E. M., & Tötzl, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-821666-8.00039-6
Indirect Cold Atmospheric Pressure Plasma treatment on Melanoma and Fibroblast Cells
(2020) · Letters in Applied NanoBioScience · doi:10.33263/lianbs102.21172125
Peeper, D. S., Schieven, S. M., Traets, J. J. H., Velds, A., de Rink, I., Nieto, J. S., Song, J., Vliet, A. V., George, A., Nieuwland, M., et al. (2025) · Research Square · doi:10.21203/rs.3.rs-6506453/v1
Wu, N., Sun, H., Sun, Q., Zhang, F., Ma, L., Hu, Y., & Cong, X. (2023) · Figshare · doi:10.6084/m9.figshare.22790567
Zheng, Q., Yang, Q., Zhou, J., Gu, X., Zhou, H., Dong, X., Zhu, H., & Chen, Z. (2021) · Figshare · doi:10.6084/m9.figshare.14889922
Metadata
- Authors
- Bai, X., Fisher, D. E., & Flaherty, K. T.
- Affiliations
- Harvard University (US)
- Corresponding author
- Flaherty, Keith T.
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2019-04-09
- Volume
- 16
- Issue
- 9
- Pages
- 549-562
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- PMC
- PMC7185899
- OpenAlex
- W2936119023
- Cited by
- 107
- References
- 243
- Citations by year
- 2026: 7 · 2025: 20 · 2024: 7 · 2023: 10 · 2022: 9 · 2021: 24 · 2020: 20 · 2019: 10
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (U54CA224068, P01CA163222)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR043369)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › Cutaneous Melanoma Detection and Management
- Keywords
- melanoma, treatment resistance, MITF, interferon-gamma, cell state dynamics, targeted therapy resistance, immunotherapy resistance, metastatic melanoma
- MeSH terms
- Humans, Interferon-gamma, Melanoma, Models, Biological, Signal Transduction, Drug Resistance, Neoplasm, Microphthalmia-Associated Transcription Factor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
