Meme Kanserinde PD-1/PD-L1 Hedefli Tedaviler

Yıl 2023, Cilt: 4 Sayı: 2, 55 - 61, 30.04.2023

Güneş Özen Eroğlu İlham Yaylım Uğur Gezer Dürdane Serap Kuruca

Öz

Meme kanseri, kadınlarda en yaygın görülen kanserlerden biridir ve
dünyadaki en yüksek insidansa sahip kanser türüdür. Meme kanseri
gelişiminde cinsiyet, yaş, östrojen düzeyi, aile öyküsü, gen mutasyonları
ve sağlıksız yaşam tarzı gibi çok sayıda risk faktörü bulunmaktadır.
Mevcut tedavi seçenekleri cerrahi, radyoterapi, hormonal tedaviler,
kemoterapi ve hedefe yönelik tedavilerdir. Hedefe yönelik tedavilerin
içinde immünoterapi son yıllarda oldukça yaygın bir tedavi stratejisi
olarak karşımıza çıkmaktadır.
Meme kanseri immün sistemden bağımsız bir kanser olduğu düşüncesinin
aksine, artık meme kanserinin immün temelli bir kanser türü
olduğu bilinmektedir. Bu kapsamda diğer kanser türlerinde olduğu
gibi, meme kanserinde de immünoterapinin hedeflediği moleküllerden
programlanmış hücre ölümü-1 (PD-1) ve programlanmış hücre
ölümü ligandı-1 (PD-L1) ile yapılan çok sayıda çalışma bulunmaktadır.
PD-1 ve PD-L1 hedefli tedaviler günümüzde meme kanseri tedavisinde
uygulanmaktadır. Meme kanseri alt tipleri olarak ele alındığında;
farklı alt tipler arasında heterojen bir dağılım olmakla birlikte tümör
hücrelerinde artmış PD-L1 ekspresyonu gözlenmektedir. Ayrıca, PDL1
ekspresyonu, genç yaş, ileri evre, tümör infiltre eden lenfositlerin
(TIL’ler) varlığı ve agresif moleküler alt tipler ile pozitif korelasyon göstermektedir.
Şimdilik sadece üçlü negatif meme kanserinin (TNMK)
tedavisinde yer alan immünoterapi, yapılacak daha fazla araştırma sonucunda,
diğer meme kanseri alt tiplerinde de kombinasyon ya da tek
tedavi olarak yer alabilecektir.
Meme kanseri tedavisinde, PD-1 ve PD-L1 düzenlemesinin ayrıntılı
mekanizmasını anlamak; tedavilere direncin üstesinden gelinmesi ve
daha iyi klinik sonuçlara ulaşılması açısından büyük önem taşımaktadır.
Bu derlemede meme kanserinde PD-1 ve PD-L1 hedefli tedavilerin
incelenmesi hedeflenmiştir.

Anahtar Kelimeler

meme kanseri, PD-1, PD-L1, immünoterapi

PD-1/PD-L1 Targeted Therapies in Breast Cancer

Öz

Breast cancer is one of the most common cancers among women and has
the highest incidence globally. Many risk factors for breast cancer progression include gender, age, estrogen level, family history, gene mutations,
and unhealthy lifestyle. Besides, current treatment options are surgery, radiotherapy, hormonal treatments, chemotherapy, and targeted therapies.
Among the targeted therapies, Immunotherapy has emerged as a very
common treatment strategy in recent years. Contrary to the thought that
breast cancer is an immune system-independent cancer, it is presently acknowledged that breast cancer is an immune-based cancer type. In this
context—as in other cancer types—many studies are conducted with programmed cell death-1 (PD-1) and programmed cell death ligand 1 (PD-L1)
molecules targeted by Immunotherapy in breast cancer. PD-1 and PD-L1
targeted therapies are currently used to treat breast cancer. Although there
is a heterogeneous distribution among different subtypes, increased PD-L1
expression is observed in tumor cells—when considering breast cancer
subtypes. Moreover, PD-L1 expression correlates positively with young age,
advanced stage, presence of tumor-infiltrating lymphocytes (TILs), and aggressive molecular subtypes. Therefore, Immunotherapy, which is currently
only used in the treatment of triple-negative breast cancer (TNBC), may be
used as a combination of treatment or single treatment procedure in other
breast cancer subtypes—after further research. To better understand the
detailed mechanism of PD-1 and PD-L1 regulation in breast cancer treatment, overcoming resistance to treatments and achieving better clinical
outcomes is important. This review aims to investigate PD-1 and PD-L1
targeted therapies in breast cancer.

Anahtar Kelimeler

breast cancer, PD-1, PD-L1, immunotherapy

Kaynakça

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