Blocking blood vessel formation through anti-angiogenic therapy may kill cancerous tumours, but it can also cause potentially deadly side-effects for patients – a dilemma that Dr. Andras Nagy and his TFRI-funded team is determined to overcome.
“We are working on minimizing the harm anti-angiogenic drugs do to the healthy parts of the body while at the same time maximizing their efficacy,” said Dr. Nagy, senior scientist at Mt. Sinai Hospital’s Lunenfeld-Tanenbaum Research Institute in Toronto.
Cancerous tumours need oxygen to grow and metastasize, and new blood vessels are constantly being formed to “feed” the tumours. Anti-angiogenic therapy blocks the formation of these blood vessels and “starves the tumour to death.” It can also cause serious side effects such as kidney damage, hypertension, ulcers, severe headaches and stroke.
Dr. Nagy and his research team have partnered with five other laboratories to push the front line of knowledge in understanding the complexity of anti-angiogenic treatments.
“Despite the significant amount of research still needed to eliminate all the risk, anti-angiogenic therapy and targeting the tumour environment are among the most promising approaches to treat cancer,” said Dr. Nagy.
The Quaggin lab is focusing on protecting the kidneys and other organs from being damaged during anti-angiogenic therapy, while the Pawson lab is researching how “disruptions of cell-cell interactions” may cause cancer. Meanwhile, the Nagy’s lab is investigating the effects of anti-angiogenic therapies on normal physiology, such as the immune system.
Led by the Wrana lab, the team is also expanding their studies to look at other non-tumour cell components of the tumours, called the tumour stroma.
“We want to see how the non-tumour component of a solid tumour is playing a role not only in the progression of the tumour growth, but also in metastasis,” he said.
Dr. Nagy says his team’s findings so far are “very exciting and interesting” – and may one day lead to a cure for cancer.
“We are proposing to introduce the tools that have been developing in the rapidly emerging stem cell field to better understand the molecular and cellular mechanisms playing roles in cancer progression and eventually gain a total control on this devastating disease.”
Editor’s note: Dr. Nagy’s work on reprogramming somatic cells to stem cells was published in Nature on Dec. 11, 2014. Dr. Nagy led a team of 50 scientists from around the world, mapping out the process of generating stem cell on a daily resolution basis. The team also discovered a new stem cell type, the F-cells, named for its fuzzy appearance. Reprogramming is the journey an adult cell takes as it changes into a stem cell.
Project Title: The Terry Fox New Frontiers Program Project Grant in the Genetic Analysis of Signaling Pathways for Vascular Development and Tumour Angiogenesis (2010-2015)
Investigators: Andras Nagy, Anthony Pawson, Jeff Wrana, and Susan Quaggin; Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Hao Ding; University of Manitoba, Janet Rossant; Hospital for Sick Children