Oncotecture

Oncotecture is the pattern of gene expression and associated protein activity that governs tumor behavior. It stems from the insight that this pattern is almost from patient to patient, regardless of the triggering mutation. This approach posits that developing interventions that affect such patterns is easier than addressing the triggering mutations.[1][2]

Mutation analysis

A genetic analysis study found that only 6.4% of tumors could be paired with a drug aimed specifically at a specific mutation. Few common cancer mutations are common and fewer have drugs that target them. The many other triggering mutations are rare and therefore unlikely to become research targets.[1]

Process

The oncotecture of a cancer derives from the gene-expression profiles (gene activity) of that cancer. This reveals the quantities and identities of the associated proteins. The relevant proteins are those involved in regulating cell growth and division via signalling pathways whereby one protein changes the behavior of potentially many others. These proteins in turn activate other genes, resulting in a cascading network of activity.[1]

Master regulator proteins

These networks have a few “master regulator” proteins that control large numbers of other proteins.[1]

As of 2016 data from 20,000 tumor samples and maps for 36 types of tumor had been completed. Some 300 proteins are master regulator candidates. They mostly regulate the process of copying information in DNA into messenger molecules.[1]

One candidate master regulator is an oestrogen-receptor that is involved in breast cancer that controls the expression of many genes. Tamoxifen has proven effective against this target. A second example is Bruton’s tyrosine kinase, which regulates white blood cell malignancies.

Improperly controlled master regulators can reinforce themselves or each other, leading to runaway growth. In aggressive prostate cancer, proteins FOXM1 and CENPF reinforce each other, inadvertently promoting tumor growth. In glioblastoma three proteins collaborate similarly. Similarly two master-regulator proteins govern the malignancy of small-cell lung cancer.[1]

Some known and suspected master regulators are in protein classes that are difficult to affect with drugs. Further not all of the master regulators identified by modeling have been shown to act as regulators.[1]

As of 2016 research mainly focused on in vitro and mouse models.[1]

See also

References

  1. 1 2 3 4 5 6 7 8 "A new type of molecular medicine may be needed to halt cancers". The Economist. 2016-12-17. ISSN 0013-0613. Retrieved 2017-01-31.
  2. ↑ Califano, Andrea; Alvarez, Mariano J. "The recurrent architecture of tumour initiation, progression and drug sensitivity". Nature Reviews Cancer. 17 (2): 116–130. doi:10.1038/nrc.2016.124.
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