Neuentwicklungen in der Neuro-Onkologie

2011 ◽  
Vol 02 (02) ◽  
pp. 89-93
Author(s):  
U. Schlegel

ZusammenfassungDie Standardtherapie des Glioblastoms im Erwachsenenalter besteht aus operativer Resektion, Bestrahlung der erweiterten Tumorregion begleitet von einer kontinuierlichen Temozolomidtherapie, gefolgt von sechs Zyklen einer adjuvanten Temozolomidtherapie. Therapiestudien mit dem Ziel, diese Standardtherapie zu verbessern, werden mit dem Integrinantagonisten Cilengitide, mit Tyrosinkinaseinhibitoren, mit dem PKC-β-Hemmer Enzastaurin, mit Neoangiogenesehemmern und mit anderen Substanzen durchgeführt. In der Rezidivtherapie werden unter anderem intensivierte Chemotherapieprotokolle und der Neoangiogenesehemmer Bevacizumab eingesetzt. In der Primärtherapie und im Rezidiv enttäuscht haben targeted therapies mit „small molecules“. Für die anaplastischen Gliome, WHO Grad III, hat die NOA-04-Studie einen neuen Therapiestandard definiert. Obwohl es keine „Standardtherapie“ der primären ZNS-Lymphome (PZNSL) gibt, soll primär eine Methotrexat-(MTX)-basierte systemische Chemotherapie eingesetzt werden. Eine primäre Strahlentherapie der PZNSL allein wird nicht empfohlen und ihr Einsatz als konsolidierende Maßnahme nach einer MTX-basierten Chemotherapie bringt nach neuesten Daten keinen Überlebensvorteil. Die Therapie der Wahl bei PZNSL besteht in einer MTX-basierten Polychemotherapie. Bei Patienten unter 60 werden damit kurative Therapieansätze verfolgt. In Deutschland gibt es gut organisierte Studiengruppen. Die Patienten sollten möglichst alle innerhalb dieser Studien behandelt werden.

2010 ◽  
Vol 29 (11) ◽  
pp. 747-752
Author(s):  
U Schlegel

ZusammenfassungDie Standardtherapie des Glioblastoms im Erwachsenenalter besteht aus operativer Resektion, Bestrahlung der erweiterten Tumorregion begleitet von einer kontinuierlichen Temozolomidtherapie, gefolgt von sechs Zyklen einer adjuvanten Temozolomidtherapie. Therapiestudien mit dem Ziel, diese Standardtherapie zu verbessern, werden mit dem Integrinantagonisten Cilengitide, mit Tyrosinkinaseinhibitoren, mit dem PKC-β-Hemmer Enzastaurin, mit Neoangiogenesehemmern und mit anderen Substanzen durchgeführt. In der Rezidivtherapie werden unter anderem intensivierte Chemotherapieprotokolle und der Neoangiogenesehemmer Bevacizumab eingesetzt. In der Primärtherapie und im Rezidiv enttäuscht haben targeted therapies mit “small molecules”. Für die anaplastischen Gliome, WHO Grad III, hat die NOA-04-Studie einen neuen Therapiestandard definiert. Obwohl es keine “Standardtherapie” der primären ZNS-Lymphome (PZNSL) gibt, soll primär eine Methotrexat-(MTX)-basierte systemische Chemotherapie eingesetzt werden. Eine primäre Strahlentherapie der PZNSL allein wird nicht empfohlen und ihr Einsatz als konsolidierende Maßnahme nach einer MTX-basierten Chemotherapie bringt nach neuesten Daten keinen Überlebensvorteil. Die Therapie der Wahl bei PZNSL besteht in einer MTX-basierten Polychemotherapie. Bei Patienten unter 60 werden damit kurative Therapieansätze verfolgt. In Deutschland gibt es gut organisierte Studiengruppen. Die Patienten sollten möglichst alle innerhalb dieser Studien behandelt werden.


2021 ◽  
Vol 12 ◽  
Author(s):  
Mengda Xu ◽  
Jiangping Song

Targeted therapy refers to exploiting the specific therapeutic drugs against the pathogenic molecules (a protein or a gene) or cells. The drug specifically binds to disease-causing molecules or cells without affecting normal tissue, thus enabling personalized and precision treatment. Initially, therapeutic drugs included antibodies and small molecules, (e.g. nucleic acid drugs). With the advancement of the biology technology and immunotherapy, the gene editing and cell editing techniques are utilized for the disease treatment. Currently, targeted therapies applied to treat cardiovascular diseases (CVDs) mainly include protein drugs, gene editing technologies, nucleic acid drugs and cell therapy. Although targeted therapy has demonstrated excellent efficacy in pre-clinical and clinical trials, several limitations need to be recognized and overcome in clinical application, (e.g. off-target events, gene mutations, etc.). This review introduces the mechanisms of different targeted therapies, and mainly describes the targeted therapy applied in the CVDs. Furthermore, we made comparative analysis to clarify the advantages and disadvantages of different targeted therapies. This overview is expected to provide a new concept to the treatment of the CVDs.


2020 ◽  
Author(s):  
Adnan Shami Shah ◽  
Xiaofu Cao ◽  
Andrew C. White ◽  
Jeremy M. Baskin

ABSTRACTMelanoma patients incur substantial mortality, despite promising recent advances in targeted therapies and immunotherapies. In particular, inhibitors targeting BRAF-mutant melanoma can lead to resistance, and no targeted therapies exist for NRAS-mutant melanoma, motivating the search for additional therapeutic targets and vulnerable pathways. Here, we identify a regulator of Wnt/β-catenin signaling, PLEKHA4, as a factor required for melanoma proliferation and survival. PLEKHA4 knockdown in vitro leads to lower Dishevelled levels, attenuated Wnt/β-catenin signaling, and a block of progression through the G1/S cell cycle transition. In mouse xenograft models, inducible PLEKHA4 knockdown attenuated tumor growth in BRAF- and NRAS-mutant melanomas and synergized with the clinically used inhibitor encorafenib in a BRAF-mutant model. As an E3 ubiquitin ligase regulator with both lipid and protein binding partners, PLEKHA4 presents several opportunities for targeting with small molecules. Our work identifies PLEKHA4 as a promising drug target for melanoma and clarifies a controversial role for Wnt/β-catenin signaling in the control of melanoma proliferation.


Author(s):  
Michael G Mccusker ◽  
Katherine A. Scilla ◽  
Christian Rolfo

2009 ◽  
Vol 20 ◽  
pp. vi35-vi40 ◽  
Author(s):  
P. Hersey ◽  
L. Bastholt ◽  
V. Chiarion-Sileni ◽  
G. Cinat ◽  
R. Dummer ◽  
...  

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3060-3060
Author(s):  
Pauline Corbaux ◽  
Mevidette El Madani ◽  
Michel Tod ◽  
Julien Peron ◽  
Denis Maillet ◽  
...  

3060 Background: The determination of the optimal biological dose (OBD) defined as the lowest safe dose associated with biological efficacy, appears to be a promising endpoint for defining the recommended phase 2 trial dose (RP2D) of novel oncologic targeted therapies in early-phase clinical trials. However, the clinical relevance of OBD is still unknown. We conducted a review to assess if the OBDs of molecular targeted therapies defined during early phase trials were useful during subsequent drug development and for oncologic drug approvals. Methods: A systematic review was conducted to identify all the molecular targeted therapies approved by FDA in solid and hematological malignancies, and for which early phase trials defined OBDs. The publications of efficacy trials leading to the first FDA approvals were reviewed, as were the FDA approved doses and dosing schedules, which were compared to OBDs found in the early phase trials. Results: OBDs were reported in the early phase trial articles of 39.5% (32/81) FDA approved targeted therapies from 1999 to 2017 (19 small molecules and 13 monoclonal antibodies (mAbs)). The maximum tolerated doses (MTD) had not been reached for 59.4% (19/32) of these drugs. When both MTD and OBD had been defined, OBD were lower than MTD in 84.6% of cases, and equal for the others. The OBDs were chosen as the RP2Ds for 56.3% of the molecules. In that case, the final FDA approved doses were consistent with the OBDs for 83.3% of the drugs. These percentages did not differ in between small molecules and mAbs. OBDs mainly relied on indirect effects on the involved signaling pathway elements for small molecules (11/19, 57.9%), and on involved receptor occupancies for mAbs (6/13, 46.2%). In total, 23.5% of all FDA approved molecular targeted therapies were approved at their OBDs. Conclusions: Although still poorly investigated, OBD may represent a relevant complementary endpoint in in early phase trials of novel anti-cancer targeted therapies, as OBDs are selected as the final FDA approved doses in 83.3 % of cases when chosen as the RP2Ds, which is much higher than the previously reported 58.0 % when MTDs are chosen as the RP2Ds (Fontes-Jardim et al. JNCI 2015).


2005 ◽  
Vol 12 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Philip Kuriakose

Background: The introduction of monoclonal antibodies, either as native molecules or conjugated to radioisotopes or other toxins, has led to new therapeutic options for patients with hematologic malignancies. In addition, the use of small molecules against specific cell surface receptors, enzymes, and proteins has become an important strategy in the treatment of such disorders. Methods: The author reviewed the published clinical trials of monoclonal antibody and other targeted therapies in hematologic malignancies. Results: Results from several trials demonstrate a therapeutic benefit for the use of monoclonal antibodies (either native or conjugated) and other targeted therapies, used alone or in combination with standard cytotoxic chemotherapy. Conclusions: Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders. Nevertheless, additional studies are needed to determine where and when such management fits into a therapeutic regimen for any given disorder, whether upfront or as salvage therapy, alone or in combination with chemotherapy (concurrent or sequential).


Proceedings ◽  
2019 ◽  
Vol 22 (1) ◽  
pp. 14
Author(s):  
Matos ◽  
Viña ◽  
Santana ◽  
Uriarte

Neurodegenerative diseases are becoming increasingly prevalent with the aging of the generalpopulation [...]


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