DIŞA ATIM POMPA SİSTEMLERİ VE BU SİSTEMLERİN KANSER TEDAVİSİNDEKİ ETKİNLİKLERİ

Year 2019, Volume: 3 Issue: 1, 54 - 69, 31.01.2019

Elvan Bakar , Dilek Özgen Gülyenli

Abstract

ÖZET

            Membranlar hücreleri çevresinde
ayıran, lipit, proteinler ve karbonhidratlardan oluşan çift tabakalı yapılardır.
Çeşitli moleküllerin hücre zarı boyunca taşınmasını sağlayan sistemler arasında
hücre zarına yerleşmiş taşıyıcı proteinler bulunmaktadır.

            Kanser, kontrolsüz hücre
çoğalmasıyla karakterize bir grup hastalığın genel adıdır. Ortalama ömrün
uzaması gibi çeşitli etkenler ile kanser görülme sıklığı artmaktadır. Kanserin
tedavisi önündeki en önemli engellerden bir tanesi, kanser hücrelerinin
kemoterapötiklere karşı geliştirdikleri çoklu ilaç direncidir. Bu dirence sebep
olan en önemli etkenlerden birisi ABC taşıyıcı proteinleridir. Günümüze kadar
keşfedilmiş 49 üyesi bulunan bu protein süper ailesinin, in vivo şartlarda
çoklu ilaç direnci ile ilişkili olduğu belirlenmiş 4 üyesi bulunmaktadır.
Bunlar P-glikoprotein (MDR1), çoklu ilaç direnci ilişkili protein (MRP1), göğüs
kanseri direnç proteini (BCRP) ve ABCC10’dur. Bu proteinler, kimyasal yapısı ve
etki mekanizmaları bakımından birbirinden çok farklı pek çok antikanser ilacını
hücre dışına atarak, kanser hücrelerinin kemoterapötiklere direnç
geliştirmesine neden olmaktadır.

            Kanser hücrelerinde oluşan çoklu
ilaç direncini atlatmak ve bu hücreleri antikanser ilaçlarına tekrar duyarlı
hale getirmek için denenen stratejilerden birisi, antikanser ilaçların p-gp
inhibitörleri ile birlikte verilmesidir. Bu amaçla 3 nesil p-gp inhibitörü
geliştirilmiştir. Henüz klinik çalışmalarda başarı gösteremeyen bu
inhibitörler, kanser tedavisi açısından üzerinde durulması gereken çok önemli
bir alanı oluşturmaktadır.

 

ABSTRACT

Membranes,
which separate the cells from their environment, are two-layered structures
composed of lipits, proteins and carbohydrates. One of the systems that allow
the transport of various molecules accros cell membranes are carrier proteins
that are located on the cell membrane.

Cancer
is the general name of a group of diseases characterized by uncontrolled cell
proliferation. The incidence of cancer is increasing with various factors such
as the average life span. One of the most important obstacles to cancer
treatment is multidrug resistance, which cancer cells develop against
chemotherapeutics. ABC carrier proteins are one of the most important factors
that cause this resistance. Until today 49 members of this protein superfamily
has been discovered, there are 4 members who are found to be associated with
multiple drug resistance in vivo conditions. These are P-glycoprotein (MDR1),
multidrug resistance-associated protein (MRP1), breast cancer resistance
protein (BCRP) and ABCC10. These proteins can efflux many different anticancer
drugs which are different from each other in terms of chemical structure and
mechanism of action and cause cancer cells to develop resistance to
chemotherapeutics.

One
strategy that has been tried to overcome the multiple drug resistance that
occurs in cancer cells and make these cells susceptible to anticancer drugs is
the co-administration of anticancer drugs with p-gp inhibitors. Three
generations of p-gp inhibitors have been developed for this purpose. These
inhibitors, which have not yet been successful in clinical trials, constitute a
very important area to be addressed in terms of cancer treatment.

Keywords

ABC taşıyıcılar, çoklu ilaç direnci

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