scholarly journals Molecular Features and Targeted Therapies in Extrahepatic Cholangiocarcinoma: Promises and Failures

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3256 ◽  
Author(s):  
Alessandro Rizzo ◽  
Simona Tavolari ◽  
Angela Dalia Ricci ◽  
Giorgio Frega ◽  
Andrea Palloni ◽  
...  
Keyword(s):  
Targeted Therapies ◽  
Anatomical Location ◽  
Therapeutic Approaches ◽  
Extrahepatic Cholangiocarcinoma ◽  
Future Directions ◽  
Molecular Features ◽  
Heterogenous Group ◽  
Systemic Treatments ◽  
Molecular Landscape ◽  
Hepatobiliary Tumors

Biliary tract cancers (BTCs) include a heterogenous group of aggressive malignancies with limited therapeutic options. According to their anatomical location, these hepatobiliary tumors are usually classified into intrahepatic cholangiocarcinoma (iCCA), extrahepatic cholangiocarcinoma (eCCA), and gallbladder cancer (GBC). Unfortunately, BTCs are often diagnosed when already metastatic, and although the advent of genomic sequencing has led to a deeper understanding of iCCA pathogenesis, very little data are currently available about the molecular landscape of eCCA. Moreover, despite novel systemic treatments emerging in BTC, the grim prognosis of eCCA patients has not changed in the past decade, and no targeted therapies have been approved so far. The aim of the current review is to provide an overview regarding molecular features and potential targeted therapies in eCCA, together with novel therapeutic approaches and future directions of translational and clinical research on this highly aggressive disease that poses many unanswered questions.

scholarly journals Integrated molecular characterisation of endometrioid ovarian carcinoma identifies opportunities for stratification

2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Robert L. Hollis ◽  
Barbara Stanley ◽  
John P. Thomson ◽  
Michael Churchman ◽  
Ian Croy ◽  
...  
Keyword(s):  
High Risk ◽  
Ovarian Carcinoma ◽  
Expression Patterns ◽  
Parp Inhibitors ◽  
Receptor Expression ◽  
Cancer Type ◽  
Sequencing Data ◽  
Molecular Features ◽  
Endometrioid Ovarian Carcinoma ◽  
Molecular Landscape

AbstractEndometrioid ovarian carcinoma (EnOC) is an under-investigated ovarian cancer type. Recent studies have described disease subtypes defined by genomics and hormone receptor expression patterns; here, we determine the relationship between these subtyping layers to define the molecular landscape of EnOC with high granularity and identify therapeutic vulnerabilities in high-risk cases. Whole exome sequencing data were integrated with progesterone and oestrogen receptor (PR and ER) expression-defined subtypes in 90 EnOC cases following robust pathological assessment, revealing dominant clinical and molecular features in the resulting integrated subtypes. We demonstrate significant correlation between subtyping approaches: PR-high (PR + /ER + , PR + /ER−) cases were predominantly CTNNB1-mutant (73.2% vs 18.4%, P < 0.001), while PR-low (PR−/ER + , PR−/ER−) cases displayed higher TP53 mutation frequency (38.8% vs 7.3%, P = 0.001), greater genomic complexity (P = 0.007) and more frequent copy number alterations (P = 0.001). PR-high EnOC patients experience favourable disease-specific survival independent of clinicopathological and genomic features (HR = 0.16, 95% CI 0.04–0.71). TP53 mutation further delineates the outcome of patients with PR-low tumours (HR = 2.56, 95% CI 1.14–5.75). A simple, routinely applicable, classification algorithm utilising immunohistochemistry for PR and p53 recapitulated these subtypes and their survival profiles. The genomic profile of high-risk EnOC subtypes suggests that inhibitors of the MAPK and PI3K-AKT pathways, alongside PARP inhibitors, represent promising candidate agents for improving patient survival. Patients with PR-low TP53-mutant EnOC have the greatest unmet clinical need, while PR-high tumours—which are typically CTNNB1-mutant and TP53 wild-type—experience excellent survival and may represent candidates for trials investigating de-escalation of adjuvant chemotherapy to agents such as endocrine therapy.

scholarly journals Diffuse Large B-Cell Lymphoma: Recognition of Markers for Targeted Therapy

Hemato ◽  
2021 ◽  
Vol 2 (2) ◽  
pp. 281-304
Author(s):  
Laura Tomas-Roca ◽  
Marta Rodriguez ◽  
Ruth Alonso-Alonso ◽  
Socorro M. Rodriguez-Pinilla ◽  
Miguel Angel Piris
Keyword(s):  
Targeted Therapy ◽  
B Cells ◽  
B Cell ◽  
B Cell Lymphoma ◽  
Therapeutic Approaches ◽  
Molecular Features ◽  
Molecular Variants ◽  
The Status ◽  
Underlying Causes ◽  
Large B Cell

Diffuse large B-cell lymphomas (DLBCL)s, the most common type of Non-Hodgkin’s Lymphoma, constitute a heterogeneous group of disorders including different disease sites, strikingly diverse molecular features and a profound variability in the clinical behavior. Molecular studies and clinical trials have partially revealed the underlying causes for this variability and have made possible the recognition of some molecular variants susceptible of specific therapeutic approaches. The main histogenetic groups include the germinal center, activated B cells, thymic B cells and terminally differentiated B cells, a basic scheme where the large majority of DLBCL cases can be ascribed. The nodal/extranodal origin, specific mutational changes and microenvironment peculiarities provide additional layers of complexity. Here, we summarize the status of the knowledge and make some specific proposals for addressing the future development of targeted therapy for DLBC cases.

scholarly journals Solitary Fibrous Tumors and So-Called Hemangiopericytoma

Sarcoma ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Nicolas Penel ◽  
Eric Yaovi Amela ◽  
Gauthier Decanter ◽  
Yves-Marie Robin ◽  
Perrine Marec-Berard
Keyword(s):  
Solitary Fibrous Tumor ◽  
Targeted Therapies ◽  
Standard Treatment ◽  
Tumor Biology ◽  
Special Focus ◽  
Solitary Fibrous Tumors ◽  
Systemic Treatments ◽  
Localized Disease ◽  
Definition Of ◽  
Fibrous Tumor

We have reviewed the literature data regarding the spectrum of tumors including solitary fibrous tumor and hemangiopericytoma with special focus on definition of the disease, discussion of the criteria for malignancy, and the key elements of standard treatment of localized disease. We have discussed the emerging concepts on the tumor biology and the different systemic treatments (chemotherapy and molecular-targeted therapies).

Bone-Targeted Therapies for Elderly Patients with Renal Cell Carcinoma: Current and Future Directions

Drugs & Aging ◽  
2013 ◽  
Vol 30 (11) ◽  
pp. 877-886 ◽  
Author(s):  
Thomas Roza ◽  
Lukman Hakim ◽  
Hendrik van Poppel ◽  
Steven Joniau
Keyword(s):  
Renal Cell Carcinoma ◽  
Elderly Patients ◽  
Cell Carcinoma ◽  
Targeted Therapies ◽  
Renal Cell ◽  
Future Directions

Metastatic Colorectal Cancer: Current State and Future Directions

2015 ◽  
Vol 33 (16) ◽  
pp. 1809-1824 ◽  
Author(s):  
Marwan G. Fakih
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Targeted Therapies ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Cytotoxic Agents ◽  
Braf Mutations ◽  
Curative Intent ◽  
Future Directions ◽  
Unresectable Metastatic Colorectal Cancer

Substantial improvements have been made in the management of metastatic colorectal cancer over the last two decades. The overall survival of patients diagnosed with unresectable metastatic colorectal cancer has increased from approximately 1 year during the era of fluoropyrimidine monotherapy to more than 30 months with the integration of multiple cytotoxic agents and targeted therapies. More effective therapeutic combinations have increased the rate of curative-intent surgical resections, resulting in median survival in this subgroup that exceed 5 years. Here we review the landscape of systemic therapies for unresectable metastatic colorectal cancer during the current era of targeted therapies, review the effects of RAS and BRAF mutations on clinical decision making, and reflect on future directions for the treatment of metastatic colorectal cancer.

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