The future of cancer classification — a molecular realignment

Traditionally cancers have been classified according to their organ system of origin: prostate cancer, breast cancer, color-rectal cancer, etc. For several years now, it has been evident that this historic classification system needed a major overhaul … and that overhaul is now coming closer.

In a new paper, published this week in the journal Cell, Hoadley et al. report on their genomic signature analysis of data from 3,500+ pathological specimens from 12 different types of cancer to elucidate a unified classification of these tumors into 11 major cancer subtypes. A helpful news item for the non-scientist appears on the web site of the San Francisco Chronicle.

The authors report that:

  • Five of these subtypes were very closely correlated with the older “tissue-of-origin” classification.
  • Lung squamous, head and neck, and a subset of bladder cancers appeared to coalesce into one definable subtype.
  • Bladder cancers seemed to be split into three different pan-cancer subtypes.

The new classification described by Hoadley et al. provides independent information for predicting clinical outcomes but is still, in many ways, correlated with  a cancer’s tissue of origin.

It is important to understand that prostate cancers were not included as one of the 12 tissue-of-origin cancer categories examined by Hoadley et al. in this study. And we know that there may be as many as 25 different subtypes of prostate cancer. But it is already very clear that in the not too distant future we are liable to be looking at a much more sophisticated system for the classification of the vast majority of cancers (prostate cancer included) that is based on a combination of both tissue of origin and molecular subtype. The “New” Prostate Cancer InfoLink would expect prostate cancers to be an important component of that reclassification, and we wouldn’t be at all surprised to find that prostate cancers behaved (from a molecular point of view) more like bladder cancers than some of the other types of cancers included in this study.

One Response

  1. Traditionally cancers have been classified according to their organ system of origin: prostate cancer, breast cancer, etc. New cancer classification system may revolutionize diagnoses and treatments.

    Cancers may be classified by their primary site of origin or by their histological or tissue types or even by their genetic and molecular types. Human cancer classification is currently based on the idea of cell of origin, and light and electron microscopic attributes of the cancer. Recent innovative techniques in biology have provided a wealth of information on changes in iron metabolism in cancerous cells. Future cancer treatment may be advanced by using an iron model of cancer classification.

    Cancer encompasses a class of heterogeneous diseases that differ on a cellular and molecular level — even within subtype. Rather than gradually collecting many tiny mutations, cancerous cells can dramatically acquire macromutations (large genomic leaps, tens or hundreds of structural rearrangements in genomic regions). The mechanisms of chromothripsis (chromosome shattering) are not well understood if microbiological information (cancer occurs when cellular iron overload affects DNA, RNA, chromosomes, even mitoses) is ignored. If cancer encompasses a class of local/regional iron-overload diseases (prostate cancer — local iron overload in the cells in the prostate gland; pancreatic cancer — local iron overload in the cells in the pancreas; lung cancer — local iron overload in the cells in the lung), most cancers can be adequately treated with surgical procedures and iron-chelating therapies (direct intra-tumoral injections of anti-iron agents, blood donation and iron-poor diet).

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