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Centre de recherche

Friday 18 October 2019 from 12:00 at 13:00

Scientific Conference of Friday Noon

Targeting senescence against aging and therapy resistance in cancer

Speaker

  • Peter de Keizer, PhD
    • Assistant Professor, University Medical Center Utrecht, The Netherlands
    • Scientific Founder, Co-Managing Director, Cleara Biotech B.V., Utrecht, the Netherlands

Aging and cancer are closely connected. Identifying processes that underly both might thus have broad benefits to society. As we age, our cells accumulate damage, which can eventually cause them to become “senescent”. Senescent cells cease to divide, but chronically secrete a wide range of factors that permanently alter their environment. As such, they are thought to impair tissue function and accelerate age-related diseases. In addition, they can also promote cancer progression, migration and therapy resistance by permanently enforcing a state of stemness. Senescent cells and senescence-like cancer cells pose exciting candidates for therapeutic removal.

Today, I will discuss how we identified the interaction between the damage-associated proteins FOXO4 and p53 as a pivot in senescent cell viability. Inhibition of FOXO4, or interference with its interaction with p53 using cell penetrating peptides could selectively eliminate senescent cells and target signs of aging in vivo[4]. We further developed these compounds in an attempt to make clinical translation feasible. As cancer cells that survived chemotherapy may develop a senescence-like response, we tested these improved compounds in models of therapy resistance. We found the FOXO4-p53 inhibitors to selectively eliminate therapy-resistant, but not primary, cancer cells in a broad sense. Together, this shows that, a) it may be possible to therapeutically restore health span once it has already declined and b) that therapy resistance in cancer may be overcome with the right anti-senescence drugs. It will now be crucial to dissect senescence heterogeneity and identify molecular mechanisms that dictate sensitivity or resistance. Our current research is focused on these mechanisms and preparing the translation of our FOXO4-p53 drugs to clinical trials.

 
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Updated on 10/3/2019
Created on 10/2/2019
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