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1. Biomarqueurs (BMs) associés à l’efficacité du nivolumab (NIVO) versus placebo (PBO) en adjuvant chez des patients atteints de mélanome réséqué de stade IIB/C (CA209-76K)

Author

Long, G., primary, Kirkwood, J.M., additional, Hoeller, C., additional, Grob, J.J., additional, Weber, J., additional, Taube, J., additional, Morh, P., additional, Van-Akkooi, A., additional, Loquai, C., additional, Dutriaux, C., additional, Chiarion-Sileni, V., additional, Tenney, D.J., additional, Dolfi, S., additional, Tang, H., additional, Ritchings, C., additional, Lobo, M., additional, Campigotto, F., additional, Wang, W., additional, Gastman, B.R., additional, and Del Vecchio, M., additional

Published
2023
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2. Perioperative Durvalumab for Resectable Non-Small-Cell Lung Cancer

Author

Heymach, J, Harpole, D, Mitsudomi, T, Taube, J, Galffy, G, Hochmair, M, Winder, T, Zukov, R, Garbaos, G, Gao, S, Kuroda, H, Ostoros, G, Tran, T, You, J, Lee, K, Antonuzzo, L, Papai-Szekely, Z, Akamatsu, H, Biswas, B, Spira, A, Crawford, J, Le, H, Aperghis, M, Doherty, G, Mann, H, Fouad, T, Reck, M, Cortinovis, D, Heymach, John V, Harpole, David, Mitsudomi, Tetsuya, Taube, Janis M, Galffy, Gabriella, Hochmair, Maximilian, Winder, Thomas, Zukov, Ruslan, Garbaos, Gabriel, Gao, Shugeng, Kuroda, Hiroaki, Ostoros, Gyula, Tran, Tho V, You, Jian, Lee, Kang-Yun, Antonuzzo, Lorenzo, Papai-Szekely, Zsolt, Akamatsu, Hiroaki, Biswas, Bivas, Spira, Alexander, Crawford, Jeffrey, Le, Ha T, Aperghis, Mike, Doherty, Gary J, Mann, Helen, Fouad, Tamer M, Reck, Martin, Cortinovis, Diego, Heymach, J, Harpole, D, Mitsudomi, T, Taube, J, Galffy, G, Hochmair, M, Winder, T, Zukov, R, Garbaos, G, Gao, S, Kuroda, H, Ostoros, G, Tran, T, You, J, Lee, K, Antonuzzo, L, Papai-Szekely, Z, Akamatsu, H, Biswas, B, Spira, A, Crawford, J, Le, H, Aperghis, M, Doherty, G, Mann, H, Fouad, T, Reck, M, Cortinovis, D, Heymach, John V, Harpole, David, Mitsudomi, Tetsuya, Taube, Janis M, Galffy, Gabriella, Hochmair, Maximilian, Winder, Thomas, Zukov, Ruslan, Garbaos, Gabriel, Gao, Shugeng, Kuroda, Hiroaki, Ostoros, Gyula, Tran, Tho V, You, Jian, Lee, Kang-Yun, Antonuzzo, Lorenzo, Papai-Szekely, Zsolt, Akamatsu, Hiroaki, Biswas, Bivas, Spira, Alexander, Crawford, Jeffrey, Le, Ha T, Aperghis, Mike, Doherty, Gary J, Mann, Helen, Fouad, Tamer M, Reck, Martin, and Cortinovis, Diego

Abstract

Background Neoadjuvant or adjuvant immunotherapy can improve outcomes in patients with resectable non-small-cell lung cancer (NSCLC). Perioperative regimens may combine benefits of both to improve long-term outcomes.Methods We randomly assigned patients with resectable NSCLC (stage II to IIIB [N2 node stage] according to the eighth edition of the AJCC Cancer Staging Manual) to receive platinum-based chemotherapy plus durvalumab or placebo administered intravenously every 3 weeks for 4 cycles before surgery, followed by adjuvant durvalumab or placebo intravenously every 4 weeks for 12 cycles. Randomization was stratified according to disease stage (II or III) and programmed death ligand 1 (PD-L1) expression (>= 1% or <1%). Primary end points were event-free survival (defined as the time to the earliest occurrence of progressive disease that precluded surgery or prevented completion of surgery, disease recurrence [assessed in a blinded fashion by independent central review], or death from any cause) and pathological complete response (evaluated centrally).Results A total of 802 patients were randomly assigned to receive durvalumab (400 patients) or placebo (402 patients). The duration of event-free survival was significantly longer with durvalumab than with placebo; the stratified hazard ratio for disease progression, recurrence, or death was 0.68 (95% confidence interval [CI], 0.53 to 0.88; P=0.004) at the first interim analysis. At the 12-month landmark analysis, event-free survival was observed in 73.4% of the patients who received durvalumab (95% CI, 67.9 to 78.1), as compared with 64.5% of the patients who received placebo (95% CI, 58.8 to 69.6). The incidence of pathological complete response was significantly greater with durvalumab than with placebo (17.2% vs. 4.3% at the final analysis; difference, 13.0 percentage points; 95% CI, 8.7 to 17.6; P<0.001 at interim analysis of data from 402 patients). Event-free survival and pathological complete respons

Published
2023

3. Postoperative Atrial Fibrillation in Aortic Valve Disease: A Comprehensive Analysis of Incidence and Risk Factors.

Author

Petersen, J., Narjes, L., Bazhanov, I., Taube, J., Yildirim, Y., Al, A. Y., Reichenspurner, H., and Pecha, S.

Subjects
AORTIC valve diseases, ATRIAL fibrillation, RISK assessment, AORTIC valve surgery, AORTIC stenosis
Abstract

This article examines the incidence and risk factors of postoperative atrial fibrillation (POAF) in patients with aortic valve disease who undergo aortic valve surgery (AVS). The study included 264 patients without a history of atrial fibrillation at the time of surgery. The incidence of POAF after AVS was found to be 23.1%, with arterial hypertension, dyslipidemia, and aortic valve stenosis identified as independent risk factors. The study highlights the clinical challenge posed by POAF in individuals with aortic valve disease and suggests that future research should focus on reducing its prevalence. [Extracted from the article]

Published
2024
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11. 171P Pharmacodynamic (PD) biomarker analysis from CheckMate (CM) 8KX: A multitumor study of a subcutaneous (SC) formulation of nivolumab (NIVO) monotherapy

Author

Jackson, C.G.C.A., primary, Perumal, D., additional, Lugowska, I., additional, O’Donnell, A., additional, North, R.T., additional, Calvo Ferrandiz, P.A., additional, Latten-Jansen, L.M., additional, Sánchez, C.G., additional, Medina Rodríguez, L.M., additional, Santoro, A., additional, Li, L., additional, Sidik, K., additional, Tang, T., additional, Deutsch, J.S., additional, Taube, J., additional, Horak, C., additional, Ravimohan, S., additional, and Lonardi, S., additional

Published
2022
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16. Nivolumab vs placebo dans le traitement adjuvant des patients atteints d’un mélanome de stade IIB/C : résultats à 3 ans de l’étude CheckMate 76K (CM 76K)

Author

Long, G., Del Vecchio, M., Hoeller, C., Weber, J., Grob, J.J., Morh, P., Grabbe, S., Dutriaux, C., Chiarion-Sileni, V., Mackiewicz, J., Rutkowski, P., Arenberger, P., Quéreux, G., Meniawy, T., Ascierto, P.A., Taube, J., Nassar, A., Wang, W., and Kirkwood, J.M.

Abstract

Les patients (pts) atteints d’un mélanome réséqué de stade IIB/C présentent un risque élevé de récidive, similaire à celui des pts atteints d’un mélanome réséqué de stade IIIB. L’essai CM 76K (NCT04099251) a démontré une réduction significative du risque de récidive ou de décès avec le nivolumab (NIVO) par rapport au placebo (PBO) chez les pts atteints d’un mélanome de stade IIB/C et ayant eu une résection complète. Les données actualisées avec un suivi de 3 ans sont présentées ici.

Published
2024
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27. Does the vestibular system contribute to head direction cell activity in the rat?

Author

Brown, J. E, Yates, B. J, Taube, J. S, and Oman, C. M

Subjects
Life Sciences (General)
Abstract

Head direction cells (HDC) located in several regions of the brain, including the anterior dorsal nucleus of the thalamus (ADN), postsubiculum (PoS), and lateral mammillary nuclei (LMN), provide the neural substrate for the determination of head direction. Although activity of HDC is influenced by various sensory signals and internally generated cues, lesion studies and some anatomical and physiological evidence suggest that vestibular inputs are critical for the maintenance of directional sensitivity of these cells. However, vestibular inputs must be transformed considerably in order to signal head direction, and the neuronal circuitry that accomplishes this signal processing has not been fully established. Furthermore, it is unclear why the removal of vestibular inputs abolishes the directional sensitivity of HDC, as visual and other sensory inputs and motor feedback signals strongly affect the firing of these neurons and would be expected to maintain their directional-related activity. Further physiological studies will be required to establish the role of vestibular system in producing HDC responses, and anatomical studies are needed to determine the neural circuitry that mediates vestibular influences on determination of head direction.

Published
2002
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28. Neural correlates for angular head velocity in the rat dorsal tegmental nucleus

Author

Bassett, J. P, Taube, J. S, and Oman, C. M

Subjects
Life Sciences (General)
Abstract

Many neurons in the rat lateral mammillary nuclei (LMN) fire selectively in relation to the animal's head direction (HD) in the horizontal plane independent of the rat's location or behavior. One hypothesis of how this representation is generated and updated is via subcortical projections from the dorsal tegmental nucleus (DTN). Here we report the type of activity in DTN neurons. The majority of cells (75%) fired as a function of the rat's angular head velocity (AHV). Cells exhibited one of two types of firing patterns: (1) symmetric, in which the firing rate was positively correlated with AHV during head turns in both directions, and (2) asymmetric, in which the firing rate was positively correlated with head turns in one direction and correlated either negatively or not at all in the opposite direction. In addition to modulation by AHV, some of the AHV cells (40.1%) were weakly modulated by the rat's linear velocity, and a smaller number were modulated by HD (11%) or head pitch (15.9%). Autocorrelation analyses indicated that with the head stationary, AHV cells displayed irregular discharge patterns. Because afferents from the DTN are the major source of information projecting to the LMN, these results suggest that AHV information from the DTN plays a significant role in generating the HD signal in LMN. A model is proposed showing how DTN AHV cells can generate and update the LMN HD cell signal.

Published
2001

29. P2.04-24 Transcriptional Profiling of Neoantigen Specific T Cells in Resectable NSCLC Treated with Neoadjuvant Anti-PD-1

Author

Caushi, J., primary, Ji, Z., additional, Zhang, J., additional, El Asmar, M., additional, Anagnostou, V., additional, Cottrell, T., additional, Chan, H.Y., additional, Guo, H., additional, Merghoub, T., additional, Wolchok, J., additional, Naidoo, J., additional, Marrone, K., additional, Chaft, J., additional, Hellmann, M., additional, Gabrielson, E., additional, Taube, J., additional, Brahmer, J., additional, Velculescu, V., additional, Zhao, N., additional, Forde, P., additional, Pardoll, D., additional, Ji, H., additional, Yegnasubramanian, S., additional, and Smith, K., additional

Published
2019
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31. MA11.10 Peripheral T Cell Repertoire Evolution in Resectable NSCLC Treated with Neoadjuvant PD-1 Blockade

Author

Zhang, J., primary, Ji, Z., additional, Caushi, J., additional, El Asmar, M., additional, Anagnostou, V., additional, Cottrell, T., additional, Chan, H.Y., additional, Guo, H., additional, Merghoub, T., additional, Chaft, J., additional, Wolchok, J., additional, Reuss, J., additional, Marrone, K., additional, Naidoo, J., additional, Gabrielson, E., additional, Taube, J., additional, Brahmer, J., additional, Velculescu, V., additional, Zhao, N., additional, Hellmann, M., additional, Forde, P., additional, Pardoll, D., additional, Yegnasubramanian, S., additional, Ji, H., additional, and Smith, K., additional

Published
2019
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34. Possibility of differentiation of cochlear electrodes in radiological measurements of the intracochlear and chorda-facial angle position

Author

Diogo, I., Walliczeck, U., Taube, J., Franke, N., Teymoortash, A., Werner, J., and Güldner, C.

Subjects
Adult, Aged, 80 and over, Male, Adolescent, Cone beam computed tomography, Audiology, Cone-Beam Computed Tomography, Middle Aged, Cochlear Implantation, Facial nerve, Cochlea, Young Adult, Measurement of cochlea, Cochlear Implants, stomatognathic system, Surgery, Computer-Assisted, Child, Preschool, Humans, Female, sense organs, Cochlear implant, Child, Visualisation of cochlea, Aged
Abstract

Due to an increasing number of cochlear implantations, quality control has become more important. In addition to intraoperative biophysical measurements, radiological imaging is another possibility. An upcoming technique regarding this is Cone Beam CT (CBCT). Sixty-five data sets (35 Nucleus Contour Advance-Cochlear; 30 Flex Soft-MedEl) of postoperative imaging by CBCT (Accu-I-tomo F17, Morita, Kyoto, Japan) underwent further evaluation. Insertion angle, height of the cochlea, distance of the electrode to the medial or lateral wall, angle between chorda tympani and facial nerve and the precise position of the electrode cable in the facial-chordal angle were determined. The typical difference between the perimodiolar and lateral course of the electrodes could also be shown in radiological measurements. This demonstrates the accuracy and advantage of CBCT in visualisation of small structures with fewer metal artifacts. Furthermore, in 75% of patients, the angle of the chorda and facial nerve could be visualised. Significant differences in dependence of the electrode type for the relation of them to the facial nerve could be seen. In conclusion, CBCT achieves reliable visualisation and detailed imaging-based measurements of the intracochlear position of different cochlea electrodes. Additionally, clinically known differences can be reproduced. Even visualisation of the position of the electrode in the chorda-facial angle is possible. Therefore, CBCT is a useful tool in intra- and postoperative control of cochlear implants.Con l’incremento del numero di impianti cocleari effettuati, il controllo di qualità è divenuto sempre più importante. Oltre alle misurazioni biofisiche intraoperatorie ci si può avvalere dell’imaging radiologico. Una nuova tecnica utilizzata in questo campo è il Cone Beam CT (CBCT). Nel presente studio sono stati valutati 65 casi (35 Nucleus Contour Advance–Cochlear; 30 Flex Soft–MedEl) studiati mediante CBCT (Accu-I-tomo F17, Morita, Kyoto, Japan). Nello specifico sono stati rilevati: l’angolo di inserzione, l’altezza dell’impianto, la distanza dell’elettrodo dalla parete mediale o laterale, l’angolo tra la corda del timpano e il nervo facciale e la posizione precisa del filo dell’elettrodo nell’angolo cordo-facciale. È stato inoltre possibile valutare la differenza tra il decorso peri-modiolare e laterale degli elettrodi. I dati presentati dimostrano l’accuratezza e il vantaggio della CBCT nella visualizzazione di piccole strutture grazie al ridotto numero di artefatti da indurimento del fascio. Inoltre nel 75% dei pazienti è stato possibile visualizzare l’angolo tra la corda del timpano e il nervo facciale. È stato possibile notare differenze significative fra i vari tipi di elettrodo in funzione del tipo di rapporto con il nervo facciale. In conclusione mediante la CBCT è possibile ottenere una visualizzazione precisa e dettagliate misurazioni della posizione intracocleare dei diversi elettrodi. È persino possibile la corretta valutazione della posizione dell’elettrodo rispetto all’angolo cordo- facciale. La CBCT è quindi, dal nostro punto di vista, un utile strumento per il controllo intra e post-operatorio degli impianti cocleari.

Published
2016

36. MA04.11 Neoantigen Targeting and T Cell Reshaping in Resectable NSCLC Patients Treated with Neoadjuvant PD-1 Blockade

Author

El Asmar, M., primary, Zhang, J., additional, Caushi, J., additional, Ji, Z., additional, Anagnostou, V., additional, Cottrell, T., additional, Chan, H.Y., additional, Suri, P., additional, Guo, H., additional, Marrone, K., additional, Naidoo, J., additional, Merghoub, T., additional, Chaft, J., additional, Hellmann, M., additional, Taube, J., additional, Brahmer, J., additional, Forde, P., additional, Velculescu, V., additional, Pardoll, D., additional, Ji, H., additional, and Smith, K., additional

Published
2018
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37. Histopathological and immunophenotypic features of ipilimumab‐associated colitis compared to ulcerative colitis

Author

Adler, B. L., primary, Pezhouh, M. K., additional, Kim, A., additional, Luan, L., additional, Zhu, Q., additional, Gani, F., additional, Yarchoan, M., additional, Chen, J., additional, Voltaggio, L., additional, Parian, A., additional, Lazarev, M., additional, Lauwers, G. Y., additional, Pawlik, T. M., additional, Montgomery, E. A., additional, Jaffee, E., additional, Le, D. T., additional, Taube, J. M., additional, and Anders, R. A., additional

Published
2018
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38. Om depression

Author

Martinsen, E, Hovland, A, Kjellman, B, Taube, J, Andersson, Eva, Martinsen, E, Hovland, A, Kjellman, B, Taube, J, and Andersson, Eva

Published
2018

39. Om ångestsyndrom

Author

Hovland, A, Martinsen, EW, Taube, J, Andersson, Eva, Kjellman, B, Hovland, A, Martinsen, EW, Taube, J, Andersson, Eva, and Kjellman, B

Published
2018

42. How brand interaction in pop-up shops influences consumers’ perceptions of luxury fashion retailers.

Author

Warnaby, GC, Taube, J, Warnaby, GC, and Taube, J

Abstract

Purpose: This research explores the influence of brand interaction in pop-up shops on consumers’ perceptions of luxury fashion retailers. Design/methodology/approach: Adopting an exploratory, inductive research design, semi-structured interviews were undertaken with female respondents, consistent with the profile of both typical pop-up and ‘new luxury’ customers, who had recently visited a luxury fashion pop-up shop. Findings: Factors influencing consumers’ perceptions of the luxury brands whose pop-up shops were visited are identified relating to three key characteristics of pop-up retailing identified from a review of relevant literature, termed the temporal dimension, the promotional emphasis, and the experiential emphasis. Originality/value: This qualitative study explores the perceptions of pop-up shops qualitatively from a consumer’s perspective, providing new insights into the personal and complex motivations and attitudes of new luxury consumers.

Published
2017

43. Combination therapy with anti-PD-1, anti-TIM-3, and focal radiation results in regression of murine gliomas

Author

Kim, J. E., Patel, M. A., Mangraviti, A., Kim, E. S., Theodros, D., Velarde, E., Liu, A., Sankey, E. W., Tam, A., Xu, H., Mathios, D., Jackson, C. M., Harris-Bookman, S., Garzon-Muvdi, T., Sheu, M., Martin, A. M., Tyler, B. M., Tran, P. T., Ye, X., Olivi, A., Taube, J. M., Burger, P. C., Drake, C. G., Brem, H., Pardoll, D. M., Lim, M., Mangraviti A., Olivi A. (ORCID:0000-0002-4489-7564), Kim, J. E., Patel, M. A., Mangraviti, A., Kim, E. S., Theodros, D., Velarde, E., Liu, A., Sankey, E. W., Tam, A., Xu, H., Mathios, D., Jackson, C. M., Harris-Bookman, S., Garzon-Muvdi, T., Sheu, M., Martin, A. M., Tyler, B. M., Tran, P. T., Ye, X., Olivi, A., Taube, J. M., Burger, P. C., Drake, C. G., Brem, H., Pardoll, D. M., Lim, M., Mangraviti A., and Olivi A. (ORCID:0000-0002-4489-7564)

Abstract

Purpose: Checkpoint molecules like programmed death-1 (PD-1) and T-cell immunoglobulin mucin-3 (TIM-3) are negative immune regulators that may be upregulated in the setting of glioblastoma multiforme. Combined PD-1 blockade and stereotactic radiosurgery (SRS) have been shown to improve antitumor immunity and produce long-term survivors in a murine glioma model. However, tumor-infiltrating lymphocytes (TIL) can express multiple checkpoints, and expression of ≥2 checkpoints corresponds to a more exhausted T-cell phenotype. We investigate TIM-3 expression in a glioma model and the antitumor efficacy of TIM-3 blockade alone and in combination with anti-PD-1 and SRS. Experimental Design: C57BL/6 mice were implanted with murine glioma cell line GL261-luc2 and randomized into 8 treatment arms: (i) control, (ii) SRS, (iii) anti-PD-1 antibody, (iv) anti-TIM-3 antibody, (v) anti-PD-1 + SRS, (vi) anti-TIM-3 + SRS, (vii) anti-PD-1 + anti-TIM-3, and (viii) anti-PD-1 + anti-TIM-3 + SRS. Survival and immune activation were assessed. Results: Dual therapy with anti-TIM-3 antibody + SRS or anti-TIM-3 + anti-PD-1 improved survival compared with anti-TIM-3 antibody alone. Triple therapy resulted in 100% overall survival (P < 0.05), a significant improvement compared with other arms. Long-term survivors demonstrated increased immune cell infiltration and activity and immune memory. Finally, positive staining for TIM-3 was detected in 7 of 8 human GBM samples. Conclusions: This is the first preclinical investigation on the effects of dual PD-1 and TIM-3 blockade with radiation. We also demonstrate the presence of TIM-3 in human glioblastoma multiforme and provide preclinical evidence for a novel treatment combination that can potentially result in long-term glioma survival and constitutes a novel immunotherapeutic strategy for the treatment of glioblastoma multiforme.

Published
2017

47. Phosphorylation of serine 367 of FOXC2 by p38 regulates ZEB1 and breast cancer metastasis, without impacting primary tumor growth

Author

Werden, S J, primary, Sphyris, N, additional, Sarkar, T R, additional, Paranjape, A N, additional, LaBaff, A M, additional, Taube, J H, additional, Hollier, B G, additional, Ramirez-Peña, E Q, additional, Soundararajan, R, additional, den Hollander, P, additional, Powell, E, additional, Echeverria, G V, additional, Miura, N, additional, Chang, J T, additional, Piwnica-Worms, H, additional, Rosen, J M, additional, and Mani, S A, additional

Published
2016
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48. Bone marrow injection stimulates hepatic ductular reactions in the absence of injury via macrophage-mediated TWEAK signaling

Author

Bird, T.G., Lu, W.-Y., Boulter, L., Gordon-Keylock, S., Ridgway, R.A., Williams, M.J., Taube, J., Thomas, J.A., Wojtacha, D., Gambardella, A., Sansom, O.J., Iredale, J.P., and Forbes, S.J.

Subjects
mental disorders, behavioral disciplines and activities, eye diseases
Abstract

Tissue progenitor cells are an attractive target for regenerative therapy. In various organs, bone marrow cell (BMC) therapy has shown promising preliminary results, but to date no definite mechanism has been demonstrated to account for the observed benefit in organ regeneration. Tissue injury and regeneration is invariably accompanied by macrophage infiltration, but their influence upon the progenitor cells is incompletely understood, and direct signaling pathways may be obscured by the multiple roles of macrophages during organ injury. We therefore examined a model without injury; a single i.v. injection of unfractionated BMCs in healthy mice. This induced ductular reactions (DRs) in healthy mice. We demonstrate that macrophages within the unfractionated BMCs are responsible for the production of DRs, engrafting in the recipient liver and localizing to the DRs. Engrafted macrophages produce the cytokine TWEAK (TNF-like weak inducer of apoptosis) in situ. We go on to show that recombinant TWEAK activates DRs and that BMC mediated DRs are TWEAK dependent. DRs are accompanied by liver growth, occur in the absence of liver tissue injury and hepatic progenitor cells can be isolated from the livers of mice with DRs. Overall these results reveal a hitherto undescribed mechanism linking macrophage infiltration to DRs in the liver and highlight a rationale for macrophage derived cell therapy in regenerative medicine.

Published
2013

49. Inhibition of FOXC2 restores epithelial phenotype and drug sensitivity in prostate cancer cells with stem-cell properties

Author

Paranjape, A N, primary, Soundararajan, R, additional, Werden, S J, additional, Joseph, R, additional, Taube, J H, additional, Liu, H, additional, Rodriguez-Canales, J, additional, Sphyris, N, additional, Wistuba, I, additional, Miura, N, additional, Dhillon, J, additional, Mahajan, N, additional, Mahajan, K, additional, Chang, J T, additional, Ittmann, M, additional, Maity, S N, additional, Logothetis, C, additional, Tang, D G, additional, and Mani, S A, additional

Published
2016
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50. Future perspectives in melanoma research: meeting report from the 'Melanoma Bridge': Napoli, December 3rd-6th 2014

Author

Ascierto, PA, Atkins, M, Bifulco, C, Botti, G, Cochran, A, Davies, M, Demaria, S, Dummer, R, Ferrone, S, Formenti, S, Gajewski, TF, Garbe, C, Khleif, S, Kiessling, R, Lo, R, Lorigan, P, Mc Arthur, G, Masucci, G, Melero, I, Mihm, M, Palmieri, G, Parmiani, G, Puzanov, I, Romero, P, Schilling, B, Seliger, B, Stroncek, D, Taube, J, Tomei, S, Zarour, HM, Testori, A, Wang, E, Galon, J, Ciliberto, G, Mozzillo, N, Marincola, FM, Thurin, M, Ascierto, PA, Atkins, M, Bifulco, C, Botti, G, Cochran, A, Davies, M, Demaria, S, Dummer, R, Ferrone, S, Formenti, S, Gajewski, TF, Garbe, C, Khleif, S, Kiessling, R, Lo, R, Lorigan, P, Mc Arthur, G, Masucci, G, Melero, I, Mihm, M, Palmieri, G, Parmiani, G, Puzanov, I, Romero, P, Schilling, B, Seliger, B, Stroncek, D, Taube, J, Tomei, S, Zarour, HM, Testori, A, Wang, E, Galon, J, Ciliberto, G, Mozzillo, N, Marincola, FM, and Thurin, M

Abstract

The fourth "Melanoma Bridge Meeting" took place in Naples, December 3-6th, 2014. The four topics discussed at this meeting were: Molecular and Immunological Advances, Combination Therapies, News in Immunotherapy, and Tumor Microenvironment and Biomarkers. Until recently systemic therapy for metastatic melanoma patients was ineffective, but recent advances in tumor biology and immunology have led to the development of new targeted and immunotherapeutic agents that prolong progression-free survival (PFS) and overall survival (OS). New therapies, such as mitogen-activated protein kinase (MAPK) pathway inhibitors as well as other signaling pathway inhibitors, are being tested in patients with metastatic melanoma either as monotherapy or in combination, and all have yielded promising results. These include inhibitors of receptor tyrosine kinases (BRAF, MEK, and VEGFR), the phosphatidylinositol 3 kinase (PI3K) pathway [PI3K, AKT, mammalian target of rapamycin (mTOR)], activators of apoptotic pathway, and the cell cycle inhibitors (CDK4/6). Various locoregional interventions including radiotherapy and surgery are still valid approaches in treatment of advanced melanoma that can be integrated with novel therapies. Intrinsic, adaptive and acquired resistance occur with targeted therapy such as BRAF inhibitors, where most responses are short-lived. Given that the reactivation of the MAPK pathway through several distinct mechanisms is responsible for the majority of acquired resistance, it is logical to combine BRAF inhibitors with inhibitors of targets downstream in the MAPK pathway. For example, combination of BRAF/MEK inhibitors (e.g., dabrafenib/trametinib) have been demonstrated to improve survival compared to monotherapy. Application of novel technologies such sequencing have proven useful as a tool for identification of MAPK pathway-alternative resistance mechanism and designing other combinatorial therapies such as those between BRAF and AKT inhibitors. Improved surviv

Published
2015

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