Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209805%3A_____%2F15%3A%230000669" target="_blank" >RIV/00209805:_____/15:#0000669 - isvavai.cz</a>

Výsledek na webu

<a href="http://linkinghub.elsevier.com/retrieve/pii/S1044-579X(14)00099-6" target="_blank" >http://linkinghub.elsevier.com/retrieve/pii/S1044-579X(14)00099-6</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.semcancer.2014.08.002" target="_blank" >10.1016/j.semcancer.2014.08.002</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Popis výsledku v původním jazyce

The tumor microenvironment includes a complicated network of physiological gradients contributingto plasticity of tumor cells and heterogeneity of tumor tissue. Hypoxia is a key component generatingintratumoral oxygen gradients, which affect the cellular expression program and lead to therapy resis-tance and increased metastatic propensity of weakly oxygenated cell subpopulations. One of the adaptiveresponses of tumor cells to hypoxia involves the increased expression and functional activation of car-bonic anhydrase IX (CA IX), a cancer-related cell surface enzyme catalyzing the reversible conversion ofcarbon dioxide to bicarbonate ion and proton. Via its catalytic activity, CA IX participates in regulationof intracellular and extracellular pH perturbations that result from hypoxia-induced changes in cellularmetabolism producing excess of acid. Through the ability to regulate pH, CA IX also facilitates cell migra-tion and invasion. In addition, CA IX has non-catalytic function in cell adhesion and spreading. Thus, CAIX endows tumor cells with survival advantages in hypoxia/acidosis and confers an increased ability tomigrate, invade and metastasize. Accordingly, CA IX is expressed in a broad range of tumors, where itis associated with prognosis and therapy outcome. Its expression pattern and functional implications intumor biology make CA IX a promising therapeutic target, which can be hit either by immunotherapywith monoclonal antibodies or with compounds inhibiting its enzyme activity. The first strategy hasalready reached the clinical trials, whereas the second one is still in preclinical testing. Both strategiesindicate that CA IX can become a clinically useful anticancer target, but urge further efforts toward betterselection of patients for immunotherapy and deeper understanding of tumor types, clinical situationsand synthetic lethality interactions with other treatment approaches.

Název v anglickém jazyce

Hypoxia-induced carbonic anhydrase IX as a target for cancer therapy: From biology to clinical use

Popis výsledku anglicky

The tumor microenvironment includes a complicated network of physiological gradients contributingto plasticity of tumor cells and heterogeneity of tumor tissue. Hypoxia is a key component generatingintratumoral oxygen gradients, which affect the cellular expression program and lead to therapy resis-tance and increased metastatic propensity of weakly oxygenated cell subpopulations. One of the adaptiveresponses of tumor cells to hypoxia involves the increased expression and functional activation of car-bonic anhydrase IX (CA IX), a cancer-related cell surface enzyme catalyzing the reversible conversion ofcarbon dioxide to bicarbonate ion and proton. Via its catalytic activity, CA IX participates in regulationof intracellular and extracellular pH perturbations that result from hypoxia-induced changes in cellularmetabolism producing excess of acid. Through the ability to regulate pH, CA IX also facilitates cell migra-tion and invasion. In addition, CA IX has non-catalytic function in cell adhesion and spreading. Thus, CAIX endows tumor cells with survival advantages in hypoxia/acidosis and confers an increased ability tomigrate, invade and metastasize. Accordingly, CA IX is expressed in a broad range of tumors, where itis associated with prognosis and therapy outcome. Its expression pattern and functional implications intumor biology make CA IX a promising therapeutic target, which can be hit either by immunotherapywith monoclonal antibodies or with compounds inhibiting its enzyme activity. The first strategy hasalready reached the clinical trials, whereas the second one is still in preclinical testing. Both strategiesindicate that CA IX can become a clinically useful anticancer target, but urge further efforts toward betterselection of patients for immunotherapy and deeper understanding of tumor types, clinical situationsand synthetic lethality interactions with other treatment approaches.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

EB - Genetika a molekulární biologie

OECD FORD obor

—

Projekt

—

Návaznosti

R - Projekt Ramcoveho programu EK

Rok uplatnění

2015

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Seminars in cancer biology

ISSN

1044-579X

e-ISSN

—

Svazek periodika

31

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

13

Strana od-do

52-64

Kód UT WoS článku

000350925200007

EID výsledku v databázi Scopus

2-s2.0-84923193781