The development of cancer is not a process triggered immediately by the emergence of an oncogenic mutation. There is growing evidence of the existence of an intermediate phase - hitherto poorly defined - in which mutated cells remain in a latent state, "accumulating the potential needed to grow, like a biological time bomb", explains Antonio Gentilella, professor at the Faculty of Pharmacy and Food Sciences at the University of Barcelona and head of the Cancer Metabolism Research Group at the Bellvitge Biomedical Research Institute (IDIBELL), part of the Bellvitge Campus.
Now, a study published in the journal PNAS and led by Professor Gentilella analyses this period in detail and reveals that there is a previously unknown mechanism that temporarily separates the acquisition of the mutation that triggers cancer from the emergence of a clinically detectable tumour. This is the MYC-LARP1-mTOR molecular axis, a key mechanism that links the two processes.
From mutation to tumour, via latency
For decades, the dominant model in cancer biology has argued that mutations in key genes (oncogenes) drive tumour formation more or less directly. But "there is growing evidence that these driver mutations, and those that accumulate later, may be present in apparently healthy tissues for years, even decades, without a clinically detectable tumour appearing," explains Antonio Gentilella.
The study conducted by IDIBELL and the UB explains this phenomenon. The researchers demonstrated that the oncogenic mutation (in this case, they studied the one affecting the MYC oncogene, which is involved in 60% of cancers) "primes" the cell for growth, but is not capable, on its own, of generating tumour mass. For a tumour to emerge, a second step is required: the cell must have the metabolic resources that enable it to produce biomass, that is, to grow and divide sustainably. "This finding redefines the origin of the tumour as a process that is not only genetic, but also metabolic and biosynthetic," notes Gentilella.
