Understanding cancers is based on understanding genes

Therapy for cancers is currently based on understanding genes.

“Where once we viewed cancer as a bewildering variety of diseases with causes too numerous to count,” Bishop writes, “now we are on the track of a single unifying explanation for how most or all cancers might arise. The track is paved with cells.”

J. Michael Bishop

But genes are not what you or your Grandfather thought they were.

One gene = one trait, not quite

One gene mutation = one disease, not entirely

An oncogene is a tumor inducing strand of DNA that may or is capable of making a defective protein.

These persisting oncogenes are manifest as post reproductive problems that evolution would not have weeded out by means of natural selection. That is because natural selection works to allay or push forward reproduction. Those traits that are debilitating are not always screened out.

Proto-Oncogenes

such as the

RAS gene

HK&N or KRAS, or NRAS, or

HRAS is bladder cancer, for example

A damaged proto-oncogene, damaged genetically (a mutant) for example is often a code problem where:

GGC ---> glycine is changed to valine ----> GTC

Genes

human chromosomes

Repressing an expression of genes in replication:

Next

Inherited tumors

RetinoBlastoma

translated from one generation to the next

on Chromosome

# 13

has a deletion or loss of genetic information to cause the tumor.

By 1986 they found the retinoblastoma gene

it is a genetic lesion that is formed.

There is a mutation in the inheritance of the tumor suppresser genes keep such tumors under control

Genetic lesions in cancer cells.

Colon cancer increases with age and the result of multiple events, or several steps from two to a dozen steps. There are 30 steps to production of prostate cancer.

Peter Noll, 1976

Every tumor represents a biological experiment that is ruthlessly selected for by evolution and demonstrates the relentless selection pressures on vital genes.

Genetic damage is the current path to cancer:

in either proto-oncogenes (GO switch or jammed accelerator)

or

tumor suppresser genes (STOP switch or defective brake)

Characteristics of cancer

excessive proliferation

impeded maturation

Unstable genetics

defective cellular suicide (cells do not die, when they should).

angiogenesis

hyperkinetic

abnormal invasiveness

metastasizes

Sun exposure to radiation

skin cancer

GCCA mutates to GTTA when irradiated by UV frequencies

p53 gene is damaged

DNA exposed to ultraviolet radiation

Bladder Cancer

can be affected by early detection

by genetic cytology

PSA test
can detect two kinds of tumors (both bad --prone to metastasize-- and benign

Defining character | Examples | Human chromosomes | paths | therapy | sources | terms

Therapy

Therapeutic regimes.

Protein handmaidens of genes can be targeted: (exquisite selectivity)

a malfunctioning switch

retinoic acid (APL) binds to mutant protein – 1987 – Leukemia (vitamin A therapy) chromosomal abnormality

Breast Cancer – Herceptin is not curative – but does help in some breast cancers

Gleevec – effective in the early phase of some types of Leukemia (resistance in tumor occurs)

Iressa can arrest the broken switch in certain cancer maladies. (Lung Cancer effective in 10%)

Defining character | Examples | Human chromosomes | paths | therapy | sources | terms

"Playing on a genetic keyboard."

He was awarded the Nobel Prize for "discovering within normal cells certain growth-controlling genes which, when mutated, play a role in initiating growth of cancerous tissues."

Dr. J. Michael Bishop, lecture, 2005, UCSB

How to Win the Nobel Prize: An Unexpected Life in Science, was published in May 2003, by Harvard University Press.

"Bishop’s story proceeds through five levels of scientific insight. First came the understanding that cancer is a cellular inheritance: it begins in a single cell and passes its malignant potential to subsequent generations of cells. Second, scientists learned that a carcinogenic event is usually set off by some external factor: cancer begins with disruptive exposure to sunlight, x-rays, smoking, a dangerous chemical. Third, that event is mutagenic: the DNA is somehow deranged, because genes are mislocated among different chromosomes (as in the "Philadelphia chromosome" associated with chronic myelogenous leukemia), or changed at a precise point, or overgrown (a hyperprevalence called "amplification"). Fourth, as they use cells to effect their own replication, certain viruses can convert benign proto-oncogenes into cancer agents—a vital finding, because the simple genetic structure of viruses is much more readily susceptible to study than is that of cellular species. Finally, the rare, truly inherited cancers reveal the repair genes and "suppressor genes" whose loss or malfunction permits other mutations to proceed to the point of tumorigenesis."

Harvard Magazine, 2003.

proto-oncogene

A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression.

Proto-oncogenes code for proteins that help to regulate cell growth and differentiation. [More]

Proto-oncogenes are often involved in signal transduction and execution of mitogenic signals, usually through their protein products.

Upon ''activation'', a proto-oncogene (or its product) becomes a tumor-inducing agent, an oncogene.

Medical News, (2014).

The Century of the Gene, published in 2000.