Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Ludwig Oxford’s David Mole and Peter Ratcliffe show interaction between transcription factors HIF and AHR, indicating a combined approach to therapy may provide greater efficacy for cancer treatment.

Hypoxia-inducible factor (HIF) and aryl hydrocarbon receptor (AHR) belong to the same family of transcription factors that have central roles in the pathogenesis of renal cancer. Compounds enabling the inhibition of these factors individually have recently been developed for the treatment of solid tumours.

Work carried out by Véronique Lafleur and colleagues in the Mole and Ratcliffe laboratories, and recently published in the Life Science Alliance journal, has shown the complex and diverse interactions between HIF and AHR in both cooperative and antagonistic manners.

AHR mRNA levels have been shown to be elevated in many types of cancer compared to normal tissue and AHR plays an important role in regulating cellular proliferation and immunity, having both pro- and anti-tumourigenic actions. Likewise, HIF is activated in many cancer types where it is associated with intra-tumour hypoxia and resistance to therapy. In clear cell renal cell carcinoma (ccRCC) tumours, competition for the common HIF-1β/ARNT subunit leads to a reciprocal competitive relationship between HIF and AHR.

These interactions indicate that therapeutic inhibition of either AHR or HIF transcription factors might lead to amplified oncogenic effects in the other pathway. This discovery raises important questions for the potential of combination therapy, raising the possibility that targeting both pathways might lead to synergistic efficacy.

Read the full paper in the Life Science Alliance journal.

Similar stories

Ludwig Oxford at 2024 AACR

Ludwig Oxford staff and students alike share their research in San Diego at the 2024 AACR Annual Meeting