A major issue related to cancer treatment is tumor cell spread. Lung cancer cell spread throughout the body is preceded by a stepwise evolution of so called pre-invasive, benign lesions, to high-grade lesions (ultimately evolving into invasive cancer).
However, not all the pre-invasive lesions progress into high-grade lesions, some of them (about 30%), indeed, spontaneously regress (through an unknown process). Discriminating those progressing to invasive cancer from those that actually regress is impossible, thus, after diagnosis, all patients are generally treated the same way, with either radiotherapy or surgery, which means that those who actually have pre-invasive lesions not progressing into high-grade lesion are, in fact, over-treated.
Though looking quite similar, pre-invasive lesions progressing into high-grade present different features at the molecular level compared to the ones that regress.
Indeed, thorough analyses have shown that progressive lesions have higher number of mutations (alterations of the DNA sequence) and high chromosome instability (meaning random loss or insertion of pieces of chromosomes during proliferation). Moreover, methylation levels (chemical modification of the DNA or proteins associated with DNA, affecting gene expression) were significantly different in the two groups, and some genes were “more active” while others were “less active”. Notably, some of the differences in methylation levels have been found in genes known for having a critical role in cancer.
Overall, when these events occur, cells acquire specific traits conferring them the ability to progress into invasive cancer.
These findings assume a great significance in light of a future exploitation of such traits to predict whether a pre-invasive lesion progresses into an invasive lesion. That, indeed, would enable to discriminate the patients that actually need treatment from those who do not, hence avoiding over treatment. Among the different molecular features considered in the analysis, chromosome instability appears as a powerful marker of progression of pre-invasive into invasive lesions. This means that if the analyses reveal chromosome instability in the pre-invasive lesions, patients should be treated for cancer, as these are likely to evolve into invasive cancer, while the others should be only periodically monitored.
Reference. Deciphering the genomic, epigenomic, and transcriptomic landscapes of pre-invasive lung cancer lesions. Teixeira, Pipinikas, Pennycuick, Lee-Six, Chandrasekharan, Beane, Morris, Karpathakis, Feber, Breeze, Ntolios, Hynds, Falzon, Capitanio, Carroll, Durrenberger, Hardavella, Brown, Lynch, Farmery, Paul, Chambers, McGranahan, Navani, Thakrar, Swanton, Beck, George, Spira, Campbell, Thirlwell, Janes. Nature Medicine 2019.