NDRG-1: Role and Potential Mechanisms of Action in Pancreatic Cancer

Öz

Pancreatic cancer (PC) is a leading cause of cancer-related mortality due to its poor prognosis, and it has the highest mortality/incidence rate in both sexes. In 2022, approximately 511,000 new cases and 467,000 PC-caused deaths were reported worldwide, with an average five-year overall survival rate of 10%. Surgical resection is the most effective treatment modality for PC; however, most patients are diagnosed at an advanced stage, which limits the efficacy of surgical intervention. The chemotherapeutic agent Gemcitabine, which is used as the standard chemotherapy agent, is only marginally effective. The FOLFIRINOX regimen, which has a higher survival rate compared to gemcitabine, exhibits high toxicity. The development of resistance to chemotherapeutic agents also negatively impacts the success of treatment, emphasising the need for multidisciplinary treatment approaches for PC. In recent studies, N-myc downregulated gene 1 (NDRG1), which interacts with tumour suppressors such as PTEN, SMAD4 and TP53 and regulates various important signalling pathways in cancer such as PI3K/AKT, TGF-β/SMAD4 and RAS/RAF/MEK/ERK, has been found to show anti-oncogenic and anti-metastatic activities in many aggressive solid tumours including pancreatic cancer. It is also suggested that NDRG1 may play a suppressive role in tumourigenesis by inhibiting multiple oncogenic signalling pathways and interacting with tumour suppressor genes. This review describes interaction of NDRG1 with tumour suppressor genes and the effects of its functions in the regulation of signalling pathways on the development of PC based on the current literature.

Anahtar Kelimeler

• NDRG-1
• PTEN
• p53
• SMAD4
• Pancreatic cancer

Proje Numarası

Yoktur

NDRG-1: Pankreas Kanserindeki Rolü ve Potansiyel Etki Mekanizmaları

Öz

Kötü prognozu nedeniyle kansere bağlı ölümlerin önde gelen nedenlerinden biri olan pankreas kanseri (PK), her iki cinsiyette de en yüksek ölüm/insidans oranına sahiptir. Dünya genelinde ortalama %10’luk beş yıllık genel sağkalım oranı olan PK için 2022 yılında yaklaşık 511.000 yeni vaka ve 467.000 PK-nedenli ölüm bildirilmiştir. Cerrahi rezeksiyon, PK tedavisinde en etkili yöntemdir ancak çoğu hastanın ileri evrede teşhis edilmesi cerrahi tedaviyi kısıtlamaktadır. Standart kemoterapi ajanı olarak kullanılan kemoterapötik ajan Gemsitabin’in etkinliği ise sınırlıdır. Gemsitabine kıyasla daha yüksek sağkalım oranına sahip FOLFIRINOX rejimi ise yüksek toksitite göstermektedir. Dahası kemoterapötik ajanlara direnç gelişimi de tedavi başarısını olumsuz etkilediğinden, günümüzde PK için multidisipliner tedavi yaklaşımları ön plandadır. Tedavideki sınırlılıklar nedeniyle yeni ve hedefe yönelik terapötik stratejilerin geliştirilmesine ihtiyaç vardır. Son çalışmalarda PTEN, SMAD4 ve TP53 gibi tümör baskılayıcılarla etkileşime girerek PI3K/AKT, TGF-β/SMAD4 ve RAS/RAF/MEK/ERK gibi kanserde önemli çeşitli sinyal yollarını düzenlenmesinde etki gösteren N-myc downregüle gen 1 (NDRG1)’in pankreas kanseri dahil birçok agresif solid tümörde anti-onkojenik ve anti-metastatik aktiviteler gösterdiği tespit edilmiştir. Ayrıca hem çoklu onkojenik sinyal yolaklarını inhibe ederek hem de tümör baskılayıcı genlerle etkileşimleri nedeniyle NDRG1'in tümör oluşumunda baskılayıcı bir rol oynayabileceği önerilmektedir. Bu derleme NDRG1’in tümör baskılayıcı genler ile etkileşimini ve sinyal yolaklarının düzenlenmesindeki fonksiyonlarının PK gelişimindeki etkilerini güncel literatüre dayanarak açıklamaktadır.

Anahtar Kelimeler

• NDRG-1
• PTEN
• p53
• SMAD4
• pankreas kanseri

Destekleyen Kurum

Yoktur.

Proje Numarası

Yoktur

Etik Beyan

Yoktur.

Teşekkür

Yazarlar İstanbul Üniversitesi Sağlık Bilimleri Enstitüsü'ne teşekkür ederler.

Kaynakça

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