|Moonshot for precision medicine|
Journal of Immunotherapy and Precision Oncology 2019 2(2):21-22
|Tackling immunotherapy resistance: Developing rational combinations of immunotherapy and targeted drugs|
Elena Cojocaru, Mariana Scaranti, Anna Minchom
Journal of Immunotherapy and Precision Oncology 2019 2(2):23-35
Mechanisms of resistance to immunotherapies are multiple and complex with components intrinsic to the tumor cell and within the immune microenvironment. We review evidence of the interaction of tumor cell signaling pathways with immune pathways and the role this plays in de novo and acquired resistance. The mitogen-activated protein kinase (MAPK) pathway activation and effects on T-cell function are discussed. Phosphoinositide 3-kinase (PI3K) pathway activation (including PTEN loss of function) correlates with T-cell inhibition and immunotherapy resistance. Wnt signaling has been implicated in T-cell function suppression. Key evidence from preclinical models exists for the role of these signaling pathways and is described. Clinical evidence is less advanced though correlation of mutations in key nodes with immune resistance provides a limited clinical correlation. Serial biomarker analysis in patients receiving targeted drugs has been attempted with notable examples including BRAF inhibition in melanoma patients resulting in dynamic changes in programmed death-ligand 1 (PD-L1) expression and tumor-infiltrating lymphocytes. Drug combinations aim to overcome mechanisms of resistance, and recent years have seen numerous combinations of targeted therapies and immune checkpoint inhibitors proposed. However, clear biological rationale and thoughtful trial designs with a translational focus are required to allow such combinations to achieve their full potential.
|Should we design clinical trials differently in the era of cancer immunotherapy?|
Journal of Immunotherapy and Precision Oncology 2019 2(2):36-39
The oncology clinical trials are evolving in the era of cancer immunotherapy. In Phase I trials, some severe immune-related adverse events occur beyond the first cycle. This is important to determine the recommended Phase II dose if the treatment duration is long. If there is no dose–response/toxicity relationship, it will not be necessary to push to the maximum tolerated dose. In Phase II trials, companion predictive biomarkers are valuable in cancers with intermediate response rates. Randomized (comparison, selection, or discontinuation) Phase II trials are needed in cancer immunotherapy combination. In Phase III trials, milestone analysis and restricted mean survival time could serve as the alternatives to hazard ratio to fit the survival kinetics of cancer immunotherapy.
|Vedolizumab Achieved Clinical and Histologic Remission in a Patient with Lung Cancer Who Had a Steroid-Refractory Upper Gastrointestinal Injury Due to Nivolumab Treatment|
Cynthia Nguyen Tran, Hamzah Abu-Sbeih, Wenyi Luo, Yang Lu, Yinghong Wang
Journal of Immunotherapy and Precision Oncology 2019 2(2):40-45
Immune checkpoint inhibitors (ICIs) have emerged as a novel therapeutic class for various malignancies. Their immune upregulation promotes significant anti-tumor effect, but simultaneously, can also result in treatment-limiting immune-related adverse events (irAEs). The data on upper gastrointestinal (GI) tract irAEs are sparse. We herein describe a case of steroid-dependent upper GI toxicity with nivolumab (an anti-programmed death [PD] protein-1) that achieved clinical and histological remission with vedolizumab treatment (a GI tract targeted anti-integrin antibody). A 65-year-old male patient with progressive lung cancer was treated with nivolumab and following 16 cycles, developed severe nausea, vomiting, and epigastric abdominal cramps requiring five hospitalizations. His initial esophagogastroduodenoscopy (EGD) showed active inflammation in both the stomach and duodenum. Nivolumab was discontinued, but despite treatment with multiple steroid courses, his symptoms always recurred during prednisone taper. Clinical remission was ultimately achieved with vedolizumab. His last EGD after five infusions of vedolizumab demonstrated resolution of inflammation. His lung cancer has since relapsed and the treatment plan was to resume nivolumab concurrently with vedolizumab. In conclusion, ICIs, such as nivolumab, have emerged as therapy for various malignancies. Their use can be associated with various irAEs including the upper GI adverse events which is uncommon. This case scenario showed that vedolizumab can provide a steroid-sparing therapeutic effect to achieve remission of upper GI irAEs even in cases where multiple steroid courses have failed.
|5th Annual immuno-oncology 360° conference: Spanning science and business to bring new therapies to patients|
Journal of Immunotherapy and Precision Oncology 2019 2(2):46-51
Τετάρτη, 10 Απριλίου 2019
Immunotherapy and Precision Oncology
Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,email@example.com, Telephone consultation 11855 int 1193,Medicine by Alexandros G. Sfakianakis Review of treatment modalities and outcomes of patients with basal cell adenocarcinoma Review of trea...
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,firstname.lastname@example.org, Telephone consultation 11855 int 1193,Medicine by Alexandros G. Sfakianakis Bupivacaine vs. lidocaine: a comparison of local anesthetic efficacy in impacted third molar surgery ...
Orchestrating phospholipid biosynthesis: Phosphatidic acid conducts and Opi1p performs [Gene Regulation]Phosphatidic acid (PA) and the conserved integral ER membrane protein Scs2p regulate localization of the transcriptional repressor Opi1p, wh...
Dupilumab Improves General Health-Related Quality-of-Life in Patients with Moderate-to-Severe Atopic Dermatitis: Pooled Results from Two Randomized, Controlled Phase 3 Clinical TrialsAbstract Introduction Patients with moderate-to-severe atopic dermatitis (AD) report a multidimensional disease burden that includes imp...
The objective of this study was to synthetize europium-doped nanohydroxyapatite using a simple aqueous precipitation method and, thereafter,...
Bound Substrate in the Structure of Cyanobacterial Branching Enzyme Supports a New Mechanistic Model [Enzymology]Branching enzyme (BE) catalyzes the formation of α-1,6-glucosidic linkages in amylopectin and glycogen. The reaction products are variable d...
Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182,00306932607174,email@example.com, Telephone consultation 11855 int 1193,Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, NRF2, p53, and p16: Predictive biomark...
2016-10-26T06-15-03Z Source: International Journal of Advances in Medicine Raghunath Anant Nagvekar, Pooja Nagvekar. Background: Early ...
Cancers, Vol. 10, Pages 8: Modification of Epigenetic Histone Acetylation in Hepatocellular CarcinomaCancers, Vol. 10, Pages 8: Modification of Epigenetic Histone Acetylation in Hepatocellular Carcinoma Cancers doi: 10.3390/cancers10010008 ...