Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance
Despite the crucial advances in understanding the biology of cholangiocarcinoma (CCA) achieved during the last decade, very little of this knowledge has been translated into clinical practice. Thus, CCA prognosis is among the most dismal of solid tumors. The reason is the frequent late diagnosis of...
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doaj-4d3a132381c340f48b934020b8d46c232021-05-31T23:58:59ZengMDPI AGCancers2072-66942021-05-01132358235810.3390/cancers13102358Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of ResistanceJose J. G. Marin0Paula Sanchon-Sanchez1Candela Cives-Losada2Sofía del Carmen3Jesús M. González-Santiago4Maria J. Monte5Rocio I. R. Macias6Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute (IBSAL), University of Salamanca, 37007 Salamanca, SpainExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute (IBSAL), University of Salamanca, 37007 Salamanca, SpainExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute (IBSAL), University of Salamanca, 37007 Salamanca, SpainDepartment of Pathology, Biomedical Research Institute (IBSAL), University Hospital of Salamanca, 37007 Salamanca, SpainDepartment of Gastroenterology and Hepatology, Biomedical Research Institute (IBSAL), University Hospital of Salamanca, 37007 Salamanca, SpainExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute (IBSAL), University of Salamanca, 37007 Salamanca, SpainExperimental Hepatology and Drug Targeting (HEVEPHARM) Group, Biomedical Research Institute (IBSAL), University of Salamanca, 37007 Salamanca, SpainDespite the crucial advances in understanding the biology of cholangiocarcinoma (CCA) achieved during the last decade, very little of this knowledge has been translated into clinical practice. Thus, CCA prognosis is among the most dismal of solid tumors. The reason is the frequent late diagnosis of this form of cancer, which makes surgical removal of the tumor impossible, together with the poor response to standard chemotherapy and targeted therapy with inhibitors of tyrosine kinase receptors. The discovery of genetic alterations with an impact on the malignant characteristics of CCA, such as proliferation, invasiveness, and the ability to generate metastases, has led to envisage to treat these patients with selective inhibitors of mutated proteins. Moreover, the hope of developing new tools to improve the dismal outcome of patients with advanced CCA also includes the use of small molecules and antibodies able to interact with proteins involved in the crosstalk between cancer and immune cells with the aim of enhancing the immune system’s attack against the tumor. The lack of effect of these new therapies in some patients with CCA is associated with the ability of tumor cells to continuously adapt to the pharmacological pressure by developing different mechanisms of resistance. However, the available information about these mechanisms for the new drugs and how they evolve is still limited.https://www.mdpi.com/2072-6694/13/10/2358biliary cancerimmunotherapypharmacoresistancetargeted therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Jose J. G. Marin Paula Sanchon-Sanchez Candela Cives-Losada Sofía del Carmen Jesús M. González-Santiago Maria J. Monte Rocio I. R. Macias |
spellingShingle |
Jose J. G. Marin Paula Sanchon-Sanchez Candela Cives-Losada Sofía del Carmen Jesús M. González-Santiago Maria J. Monte Rocio I. R. Macias Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance Cancers biliary cancer immunotherapy pharmacoresistance targeted therapy |
author_facet |
Jose J. G. Marin Paula Sanchon-Sanchez Candela Cives-Losada Sofía del Carmen Jesús M. González-Santiago Maria J. Monte Rocio I. R. Macias |
author_sort |
Jose J. G. Marin |
title |
Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance |
title_short |
Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance |
title_full |
Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance |
title_fullStr |
Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance |
title_full_unstemmed |
Novel Pharmacological Options in the Treatment of Cholangiocarcinoma: Mechanisms of Resistance |
title_sort |
novel pharmacological options in the treatment of cholangiocarcinoma: mechanisms of resistance |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2021-05-01 |
description |
Despite the crucial advances in understanding the biology of cholangiocarcinoma (CCA) achieved during the last decade, very little of this knowledge has been translated into clinical practice. Thus, CCA prognosis is among the most dismal of solid tumors. The reason is the frequent late diagnosis of this form of cancer, which makes surgical removal of the tumor impossible, together with the poor response to standard chemotherapy and targeted therapy with inhibitors of tyrosine kinase receptors. The discovery of genetic alterations with an impact on the malignant characteristics of CCA, such as proliferation, invasiveness, and the ability to generate metastases, has led to envisage to treat these patients with selective inhibitors of mutated proteins. Moreover, the hope of developing new tools to improve the dismal outcome of patients with advanced CCA also includes the use of small molecules and antibodies able to interact with proteins involved in the crosstalk between cancer and immune cells with the aim of enhancing the immune system’s attack against the tumor. The lack of effect of these new therapies in some patients with CCA is associated with the ability of tumor cells to continuously adapt to the pharmacological pressure by developing different mechanisms of resistance. However, the available information about these mechanisms for the new drugs and how they evolve is still limited. |
topic |
biliary cancer immunotherapy pharmacoresistance targeted therapy |
url |
https://www.mdpi.com/2072-6694/13/10/2358 |
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