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

Result code in 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>

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EB - Genetics and molecular biology

OECD FORD branch

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Project

—

Continuities

R - Projekt Ramcoveho programu EK

Publication year

2015

Confidentiality

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

Name of the periodical

Seminars in cancer biology

ISSN

1044-579X

e-ISSN

—

Volume of the periodical

31

Issue of the periodical within the volume

April

Country of publishing house

GB - UNITED KINGDOM

Number of pages

13

Pages from-to

52-64

UT code for WoS article

000350925200007

EID of the result in the Scopus database

2-s2.0-84923193781