7 research outputs found
Future perspectives in melanoma research: meeting report from the "Melanoma Bridge";: Napoli, December 3rd-6th 2014.
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 survival rates have also been observed with immune-targeted therapy for patients with metastatic melanoma. Immune-modulating antibodies came to the forefront with anti-CTLA-4, programmed cell death-1 (PD-1) and PD-1 ligand 1 (PD-L1) pathway blocking antibodies that result in durable responses in a subset of melanoma patients. Agents targeting other immune inhibitory (e.g., Tim-3) or immune stimulating (e.g., CD137) receptors and other approaches such as adoptive cell transfer demonstrate clinical benefit in patients with melanoma as well. These agents are being studied in combination with targeted therapies in attempt to produce longer-term responses than those more typically seen with targeted therapy. Other combinations with cytotoxic chemotherapy and inhibitors of angiogenesis are changing the evolving landscape of therapeutic options and are being evaluated to prevent or delay resistance and to further improve survival rates for this patient population. This meeting's specific focus was on advances in combination of targeted therapy and immunotherapy. Both combination targeted therapy approaches and different immunotherapies were discussed. Similarly to the previous meetings, the importance of biomarkers for clinical application as markers for diagnosis, prognosis and prediction of treatment response was an integral part of the meeting. The overall emphasis on biomarkers supports novel concepts toward integrating biomarkers into contemporary clinical management of patients with melanoma across the entire spectrum of disease stage. Translation of the knowledge gained from the biology of tumor microenvironment across different tumors represents a bridge to impact on prognosis and response to therapy in melanoma
Future perspectives in melanoma research: meeting report from the “Melanoma Bridge”: Napoli, December 3rd–6th 2014
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Six transiting planets and a chain of Laplace resonances in TOI-178
Determining the architecture of multi-planetary systems is one of the
cornerstones of understanding planet formation and evolution. Resonant systems
are especially important as the fragility of their orbital configuration
ensures that no significant scattering or collisional event has taken place
since the earliest formation phase when the parent protoplanetary disc was
still present. In this context, TOI-178 has been the subject of particular
attention since the first TESS observations hinted at a 2:3:3 resonant chain.
Here we report the results of observations from CHEOPS, ESPRESSO, NGTS, and
SPECULOOS with the aim of deciphering the peculiar orbital architecture of the
system. We show that TOI-178 harbours at least six planets in the super-Earth
to mini-Neptune regimes, with radii ranging from 1.152(-0.070/+0.073) to
2.87(-0.13/+0.14) Earth radii and periods of 1.91, 3.24, 6.56, 9.96, 15.23, and
20.71 days. All planets but the innermost one form a 2:4:6:9:12 chain of
Laplace resonances, and the planetary densities show important variations from
planet to planet, jumping from 1.02(+0.28/-0.23) to 0.177(+0.055/-0.061) times
the Earth's density between planets c and d. Using Bayesian interior structure
retrieval models, we show that the amount of gas in the planets does not vary
in a monotonous way, contrary to what one would expect from simple formation
and evolution models and unlike other known systems in a chain of Laplace
resonances. The brightness of TOI-178 allows for a precise characterisation of
its orbital architecture as well as of the physical nature of the six presently
known transiting planets it harbours. The peculiar orbital configuration and
the diversity in average density among the planets in the system will enable
the study of interior planetary structures and atmospheric evolution, providing
important clues on the formation of super-Earths and mini-Neptunes