Loss of ACE2 mediates resistance to classical treatments to renal cell carcinoma (RCC) , and treatment with a drug that could downstream ACE2, can improve tumor responses in RCC and prolong survival. Renal cell carcinoma (RCC) is the most common form of cancer of the kidney. In 2018, there were an estimated 403,000 new cases of RCC and 175,000 deaths due to kidney cancer worldwide. Currently, the 5-year survival rate for patients with metastatic RCC is only about 12 percent.
‘Angiotensin-(1-7) could provide a promising therapeutic option in patients with RCC in combination with VEGF-pathway inhibitors.’
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Current treatments include inhibitors of the VEGF and PD-1 pathways. However, resistance to therapy occurs in most patients and new combination treatments are still needed to enhance the efficacy of these current approaches.Read More..
The team, led by Beth Israel Deaconess Medical Center's (BIDMC) Rupal Bhatt, MD, PhD, and University College Cork, Ireland's Thomas Walther, PhD, published their findings in the journal Science Translational Medicine.
"Our team reported that ACE2 is a new protective molecule for RCC, and building on this finding, we show that angiotensin-(1-7), a small peptide generated by ACE2, can be used to control tumor growth in preclinical models," said co-corresponding Bhatt, a medical oncologist at BIDMC and associate professor of medicine at Harvard Medical School.
"Our findings suggest that angiotensin-(1-7) could be developed in clinical trials as a promising therapeutic option in patients with RCC in combination with current standard of care treatments and has a strong potential to improve overall survival."
ACE2 is an enzyme that belongs to the renin-angiotensin system (RAS) and antagonizes the classical angiotensin II/AT1 receptor pathway. Interestingly, it is also the receptor for the SARS-CoV2 spike protein, and its downregulation by the virus leads to the often deadly progression of acute respiratory distress syndrome in COVID-19 patients.
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Using novel and innovative methods and techniques, the authors generated multiple lines of evidence that this ACE2 down-regulation can be causative for the resistance to VEGF pathway inhibition, the inevitable consequence of this approved used class of drugs.
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"Our work shows that angiotensin-(1-7) could provide a promising therapeutic option in patients with RCC in combination with VEGF-pathway inhibitors," said co-corresponding author Walther, Professor in Pharmacology at the University College Cork.
"Resistance to VEGF-pathway inhibitors is a general problem in cancer treatment and therefore our findings have broader implications for VEGF-pathway inhibitor therapies that beyond RCC could be extended to other types of cancers."
Source-Eurekalert