Exploration of Targeted Anti-tumor Therapy: a contribution to the development of targeted therapies

2020 ◽  
Vol 1 (1) ◽  
pp. 1-2
Author(s):  
Nicola Normanno ◽  
Graham Packham
Keyword(s):  
Targeted Therapies ◽  
Tumor Therapy

scholarly journals Does systemic anti-tumor therapy increase COVID-19 risk in patients with cancer?

2021 ◽  
pp. 107815522110157
Author(s):  
Murat Ayhan ◽  
Şahin Laçin ◽  
Deniz T Özyükseler ◽  
Heves Sürmeli ◽  
Akif Doğan ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Cancer Patients ◽  
Infection Rate ◽  
Targeted Therapies ◽  
Metastatic Cancer ◽  
Tumor Therapy ◽  
Palliative Therapy ◽  
Patients With Cancer ◽  
Systemic Treatments ◽  
The Difference

Purpose We aimed to determine the COVID-19 infection rate and determine the factors that affect hospitalization and prognosis in patients receiving systemic chemotherapy (CT), immunotherapy (IT) and molecular-targeted therapies at our hospital within three months after the onset of COVID-19 pandemic. Materials and methods The patients who received systemic treatment at chemotherapy unit with diagnosis of cancer between 11 March 2020 and 11 June 2020 were included. The clinical and demographic characteristics of patients, the systemic treatments that they received (CT, IT, targeted therapies), and the stage of disease were determined. For the parameters that affect the hospitalization of COVID-19 infected patients were also determined. Results Among 1149 patients with cancer, 84 of them were infected with COVID-19, and the median age of infected patients was 61.0 (IQR: 21–84) and 60.7% of them were male. As a subtype of cancers lung cancer was more frequent in the patients who infected with COVID compared with non-infected ones and the difference was statistically significant when the underlying malignities were compared (32.1% vs 19.0%, p = 0.031). The hospitalization rate and receiving COVID-19 treatment were more frequent in metastatic patients who were receiving palliative therapy, and the difference was statistically significant ( p = 0.01, p = 0.03). In our study, infection rate was similar among patients treated with CT, IT and CT plus targeted therapy; however, fewer COVID-19 infections were seen at patients who received only targeted therapy. Conclusion COVID-19 infection is more frequent in cancer patients and tends to be more severe in metastatic cancer patients receiving anticancer treatment, and the continuation of palliative cancer treatments in these patients may cause increased cancer and infection-related morbidity and mortality.

scholarly journals Engineering of Cytolethal Distending Toxin B by Its Reducing Immunogenicity and Maintaining Stability as a New Drug Candidate for Tumor Therapy; an In Silico Study

Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 785
Author(s):  
Maryam Keshtvarz ◽  
Mahdieh Mahboobi ◽  
Marek Kieliszek ◽  
Antoni Miecznikowski ◽  
Hamid Sedighian ◽  
...  
Keyword(s):  
B Cell ◽  
Structural Stability ◽  
Targeted Therapies ◽  
Hot Spot ◽  
Tumor Therapy ◽  
3D Structure ◽  
Foreign Protein ◽  
Drug Candidate ◽  
Cytolethal Distending Toxin ◽  
B Cell Epitopes

The cytolethal distending toxin (CDT), Haemophilus ducreyi, is one of the bacterial toxins that have recently been considered for targeted therapies, especially in cancer therapies. CDT is an A-B2 exotoxin. Its catalytic subunit (CdtB) is capable of inducing DNA double strand breaks, cell cycle arrest and apoptosis in host eukaryotic cells. The sequence alignment indicates that the CdtB is structurally homologyr to phosphatases and deoxyribonucleases I (DNase I). Recently, it has been found that CdtB toxicity is mainly related to its nuclease activity. The immunogenicity of CDT can reduce its effectiveness in targeted therapies. However, the toxin can be very useful if its immunogenicity is significantly reduced. Detecting hotspot ectopic residues by computational servers and then mutating them to eliminate B-cell epitopes is a promising approach to reduce the immunogenicity of foreign protein-based therapeutics. By the mentioned method, in this study, we try to reduce the immunogenicity of the CdtB- protein sequence. This study initially screened residue of the CdtB is B-cell epitopes both linearly and conformationally. By overlapping the B-cell epitopes with the excluded conserve residues, and active and enzymatic sites, four residues were allowed to be mutated. There were two mutein options that show reduced antigenicity probability. Option one was N19F, G74I, and S161F with a VaxiJen score of 0.45 and the immune epitope database (IEDB) score of 1.80, and option two was N19F, G74I, and S161W with a VaxiJen score of 0.45 and IEDB score of 1.88. The 3D structure of the proposed sequences was evaluated and refined. The structural stability of native and mutant proteins was accessed through molecular dynamic simulation. The results showed that the mutations in the mutants caused no considerable changes in their structural stability. However, mutant 1 reveals more thermodynamic stability during the simulation. The applied approaches in this study can be used as rough guidelines for finding hot spot immunogen regions in the therapeutic proteins. Our results provide a new version of CdtB that, due to reduced immunogenicity and increased stability, can be used in toxin-based drugs such as immunotoxins.

Rapamycin-regulated Control of Antiangiogenic Tumor Therapy Following rAAV-mediated Gene Transfer

2007 ◽  
Author(s):  
Minh Nguyen ◽  
Guang Huan-Tu ◽  
Melissa Gonzalez-Edick ◽  
Victor M Rivera ◽  
Tim Clackson ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Tumor Therapy

Induktion von einem nicht-apoptotischen Zelltodes in der humane Zelllinie HepG2 nach Behandlung mit neuen Targeted Therapies

2019 ◽  
Author(s):  
PI Mester ◽  
E Aschenbrenner ◽  
K Pollinger ◽  
C Kunst ◽  
K Gülow ◽  
...  
Keyword(s):  
Targeted Therapies

Development of hypoparathyroidism due to targeted therapies

2017 ◽  
Author(s):  
Canpolat Asena Gokcay ◽  
Berna Imge Aydogan ◽  
Sule Canlar ◽  
Sevim Gullu ◽  
Murat Faik Erdogan
Keyword(s):  
Targeted Therapies

Acute pericarditis and mediastinal lymph node abscess developing after endobronchial ultrasound guided transbronchial needle aspiration

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Shingo Nishikawa ◽  
Ryo Ariyasu ◽  
Tomoaki Sonoda ◽  
Masafumi Saiki ◽  
Takahiro Yoshizawa ◽  
...  
Keyword(s):  
Lymph Node ◽  
Mediastinal Lymph Node ◽  
Tumor Therapy ◽  
Needle Aspiration ◽  
Lymph Node Biopsy ◽  
Endobronchial Ultrasound ◽  
Tumor Treatment ◽  
Ultrasound Guided ◽  
Transbronchial Needle Aspiration ◽  
Acute Pericarditis

A 27-year-old man was diagnosed with inflammatory myofibroblastic tumor, and multiple lymph node and subcutaneous metastases. After several administrations of anti-tumor therapy, he underwent mediastinal lymph node biopsy using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) to confirm tumor relapse. Five weeks later, he complained of chest pain, then rapidly developed shock due to acute pericarditis. Although he was treated with antibiotics for anaerobic bacterial infection and cardiac drainage, mediastinal lymph node abscess and pericarditis did not improve. After the surgical procedure, his physical condition dramatically improved and he was treated with another molecularly targeted therapy. Pericarditis associated with EBUS-TBNA is extremely rare. In this case, salvage was achieved by surgical drainage of the lymph node abscess and pericarditis, and long survival was obtained with further administration of anti-tumor treatment.

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