Miguel Bronchud: When does a normal or “quasi normal“ tissue really becomes a “cancer”?

Miguel Bronchud, Co-Founder & Advisory Board at Regenerative Medicine Solutions, shared a post on LinkedIn:

“To be “cancer”, or not to be? When does a normal or “quasi normal “ tissue really becomes a “cancer”? An example on how difficult it might be to truly “qualify as a cancer” we can see in prostate cancer (in some countries the commonest cancer type diagnosed in recent times).

In the UK , for instance, prostate cancers now rank top among the top causes of death from cancers (following lung cancers and gastrointestinal cancer). But, autopsy studies reveal that so called low grade 1 ( GG1 ) is so common in aging males as to be perhaps a normal aspect of aging. Pure GG1 has no capacity to metastasize. Modern diagnostic pathways focus on detecting higher-grade disease, explicitly omitting biopsy if GG 2 or higher is not suspected, so GG1 has effectively become an “incidentaloma.”

Recent spatial transcriptomics of prostate sections identifies a continuum of genomic changes—including alterations characteristic of malignancy in histologically normal regions, so the designation of cancer based entirely on conventional pathology findings increasingly seems arbitrary at least to an extent. Pathologists discussed heterogeneity and diagnostic challenges, suggesting “acinar neoplasm” as one possible alternative label. GG1 should not be considered “normal,” and absolutely requires ongoing active surveillance.

Lung cancer is by far the most common cause of cancer deaths in males accounting for around a fifth (21%) of all male cancer deaths (2017-2019).The next most common causes of cancer death in UK males are prostate (14%) and bowel (10%) cancers. Lung, prostate and bowel cancers together account for nearly half (45%) of all male cancer deaths in the UK. (Link)

But when does a “pre cancer really become a cancer”? Traditionally we were taught “when abnormal cells behave like malignant cells”, e.g. by invading normal neighboring tissue and/or spreading to loco regional lymph nodes , or distant sites (“metastasis”). For that to happen, of course, cancer cells must not only outcompete normal cells, but also escape or evade our normal immune control.

But the latter is (in my opinion and personal view) probably the key process – and yet it seems poorly understood. Not only in a pathological serious process like cancers , but also in a crucial physiological process (in Eutherian mammals) like normal pregnancy, placentation and feto maternal tolerance.

See (if you are curious ) some short personal published articles- with links to references of the original studies in a unique clinical context …

Bronchud M. H. (2018). Are aggressive epithelial cancers ‘a disease’ of Eutherian mammals? Ecancermedicalscience, 12, 840.
Bronchud M. H. (2017). Immunomodulatory pathways in both breast cancer and placental tissues: Insights from a unique clinical and genomic case report. J Clin Oncol, 35(7).”

Additional information

Source: Miguel Bronchud/LinkedIn