The malignant nature of cancer is a phenotype related to blocked apoptosis.

What is it about?

Alpha-fetoprotein (AFP) well known as an oncodevelopmental antigen and the first tumor marker discovered, through its 67 kD AFP receptor (AFPr), is thought to prevent normal aging at the cellular level in part by blocking apoptosis. At the whole host level, paradoxically this leads to aging. (Think of aged skin as having problems dying, thereby they linger and need exfoliation to reveal a more youthful appearance.) The 67 kD AFPr is highly expressed at the cell surface of over 90 % of the common adenocarcinomas (solid tumors) but is also expressed on semi-activated macrophages. HERE AFP blocks apoptosis and generates an immunosuppressive signal. These dysfunctional, lingering macrophages may contribute to immunosuppression and paradoxically also inflammation (which we now call immunosenescence). Agents which may bind and inactivate AFP or which may downmodulate its expression (such as DHEA, the youth hormone) may be useful to reverse anti-cellular senescence (or immunosenescence).

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Why is it important?

This paper (1994) may be one of the first to imply the malignant nature of cancer was a phenotype and thus not a genotype, and accordingly, a malignant tumor could be reverted to benign such as by using agents able to block AFP activity or expression. It was only in 2013 that Dr. Robert A. Weinberg received the 2013 Breakthrough Prize in Life Sciences for his work on establishing that the malignant potential of tumors is not genetically determined (Tam & Weinberg, 2013).

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