Cancer occurs when cells multiply uncontrollably, but to do so, they need fuel. More specifically, cancer cells require nutrients, which they convert into the energy they need to proliferate – a process known as cancer metabolism. But what if their energy sources were eliminated, or the process of cancer metabolism altered? Could cancer growth be manipulated, or halted altogether?
A longstanding Terry Fox New Frontiers Program Project Grant team pioneering cancer metabolism research in Canada is seeking the answers to these questions. Funded in collaboration with the Quebec Breast Cancer Federation (QBCF), the team has come to understand that the process of cancer metabolism is not only central to the development and progression of cancer, but is also extremely dynamic, meaning that it’s able to adapt to different circumstances to keep “feeding” cancer growth.
“Overall, the impact of the PPG in Targeting the Metabolic Vulnerabilities of Cancer has been to significantly expand our fundamental knowledge of cancer metabolism and how it enables cancers to establish, spread and resist therapy,” says Dr. Julie St-Pierre, professor at the University of Ottawa and one of the project’s co-leaders. “This has helped establish metabolic plasticity as an Achilles’ heel and revealed molecular mechanisms that can be exploited to dramatically improve cancer therapy.”
By developing cutting-edge, pre-clinical models, the team has been able to study cancer metabolism every step of the way – from the earliest stages to the development of metastatic and drug-resistance disease.
In doing so, they’ve identified the molecular mechanisms that guide and govern metabolic reprogramming and plasticity. According to Dr. St-Pierre, this includes understanding how genes involved in key metabolic pathways are controlled, identifying hormones and growth hormones that stimulate the cellular signalling pathways regulating metabolism and revealing the molecular circuitry that links cancer-causing genes (oncogenes) with metabolic pathways.
In a study led by PPG investigator Vincent Giguère, professor at McGill University, the team expanded this research using advanced technology to map the network of interacting proteins associated with nuclear mTOR – a kinase used in metabolic regulation – in cell-based models of normal and cancerous prostate cells. “These findings shed new light on how mTOR functions in the control of gene expression upon association with chromatin, an unexpected role for this essential regulator,” says Dr. Peter Siegel, professor at McGill University and team co-leader.
In addition to this, PPG team members have also revealed how metabolism changes in the area surrounding tumours, known as the tumour microenvironment, revealing a series of interesting connections that could have an impact on cancer treatment and prevention.
“This work has revealed intricate networks of communication and metabolic exchange between cancer cells, immune cells, adipocytes (fat cells) and other cell types, how these are affected by diet and bodyweight and how they can be targeted to block tumour growth and progression,” says Dr. Siegel.
Together, this work brings the PPG team one step closer to their goal of understanding the connection between metabolic reprogramming, metastatic progression and treatment resistance to inform and, thus, improve the effectiveness of cancer therapies.