Replies to post #19228 on NorthWest Biotherapeutics Inc (NWBO)

[flipper44]

Dok said,

I thought that most mutations did kill cells, not through apoptosis, but rather through the loss of a needed protein. If that is not the case then I need to edit some wiki content.

(Note: My frustration with someone else on the board was not the topic, it was his active admitted refusal to read any research presented to him, then pontificate on the subject, ascribe inaccurate views to other people using a straw man like technique and ignore the remaining context in responses he received. I apologize to you and the board for trying to short circuit this debating technique by sarcastically using his same technique x 10 in reverse to attempt to curtail the needless 'heated' debates. )

Anyway, in response to your question:) I tried to find something that would explain, in a noncontroversial way, the point that cancer cell progeny, on average, accumulate 60 or more mutations during the course of their ancestors' cell divisions. The logic here being that those mutations did not happen all at once, they occurred over time during cell division, and in the meantime those prior cells were capable of not only living with one mutation, but indeed procreating a lineage of cells with more and more mutations in each generation.

(Digression: Did you ever see that movie with Michael Keaton called "Multiplicity"? Michael Keaton made clones of himself so he could be more productive, but the clones made copies of themselves,

"and you know how sometimes when you make a copy of a copy, it is not quite as sharp?" -- Michael Keaton

Here is the film trailer.)

I really hope the science excerpt below is helpful to people as a relatively accepted understanding regarding current basic understanding in cancer cell mutations. Foxhound can tell us what parts are still controversial, but I think it gives everyone a foundation upon which to agree or disagree.


"Cell Division and Cancer

Cancer cells are cells gone wrong — in other words, they no longer respond to many of the signals that control cellular growth and death. Cancer cells originate within tissues and, as they grow and divide, they diverge ever further from normalcy. Over time, these cells become increasingly resistant to the controls that maintain normal tissue — and as a result, they divide more rapidly than their progenitors and become less dependent on signals from other cells. Cancer cells even evade programmed cell death, despite the fact that their multiple abnormalities would normally make them prime targets for apoptosis. In the late stages of cancer, cells break through normal tissue boundaries and metastasize (spread) to new sites in the body.

How Do Cancer Cells Differ from Normal Cells?
In normal cells, hundreds of genes intricately control the process of cell division. Normal growth requires a balance between the activity of those genes that promote cell proliferation and those that suppress it. It also relies on the activities of genes that signal when damaged cells should undergo apoptosis.

Cells become cancerous after mutations accumulate in the various genes that control cell proliferation. According to research findings from the Cancer Genome Project, most cancer cells possess 60 or more mutations. The challenge for medical researchers is to identify which of these mutations are responsible for particular kinds of cancer. This process is akin to searching for the proverbial needle in a haystack, because many of the mutations present in these cells have little to nothing to do with cancer growth.

Different kinds of cancers have different mutational signatures. However, scientific comparison of multiple tumor types has revealed that certain genes are mutated in cancer cells more often than others. For instance, growth-promoting genes, such as the gene for the signaling protein Ras, are among those most commonly mutated in cancer cells, becoming super-active and producing cells that are too strongly stimulated by growth receptors. Some chemotherapy drugs work to counteract these mutations by blocking the action of growth-signaling proteins. The breast cancer drug Herceptin, for example, blocks overactive receptor tyrosine kinases (RTKs), and the drug Gleevec blocks a mutant signaling kinase associated with chronic myelogenous leukemia.

Other cancer-related mutations inactivate the genes that suppress cell proliferation or those that signal the need for apoptosis. These genes, known as tumor suppressor genes, normally function like brakes on proliferation, and both copies within a cell must be mutated in order for uncontrolled division to occur. For example, many cancer cells carry two mutant copies of the gene that codes for p53, a multifunctional protein that normally senses DNA damage and acts as a transcription factor for checkpoint control genes.

How Do Cancerous Changes Arise?

Gene mutations accumulate over time as a result of independent events. Consequently, the path to cancer involves multiple steps. In fact, many scientists view the progression of cancer as a microevolutionary process.

A schematic diagram shows five different images of a group of cells, depicting the various stages that occur in the progression from normal, healthy cells to invasive cancer cells. Normal cells in the population are shown as light pink circles with a darker pink border and a darker pink dot in their center; they are arranged side-by-side to form a hollow ring. Hyper-proliferating, mutant cells are shown as light purple circles with a darker purple border, some of which have a dark purple dot in their center, or as blue cells. The mutant cells are shown dividing inside the ring of healthy cells where they form a dense clump that eventually fills the inside of the ring, rupturing it.

Figure 1: Microevolution of a cancer cell
A series of mutations in a cell causes it to proliferate more than its immediate neighbors. As the cluster of dividing cells grows over time, further mutations turn atypical hyperplasia into a cancer (carcinoma). The spreading of cancer cells to other tissues and organs (metastasis) occurs when the adhesion of these cancerous cells breaks down, and they are able to travel easily to new locations.

A five-part schematic shows six normal colon cells as they accumulate specific mutations and eventually develop into a large population of metastatic cancer cells. Each cell is represented as a circle containing a small, circular nucleus at its center. The color of the cells changes from beige to yellow to orange and finally red as the population becomes increasingly cancerous.

View Full-Size Image Figure 2 Figure Detail To understand what this means, consider the following: When a mutation gives a cancer cell a growth advantage, it can make more copies of itself than a normal cell can — and its offspring can outperform their noncancerous counterparts in the competition for resources. Later, a second mutation might provide the cancer cell with yet another reproductive advantage, which in turn intensifies its competitive advantage even more. And, if key checkpoints are missed or repair genes are damaged, then the rate of damage accumulation increases still further. This process continues with every new mutation that offers such benefits, and it is a driving force in the evolution of living things — not just cancer cells (Figure 1, Figure 2).

How Do Cancer Cells Spread to Other Tissues?
During the early stages of cancer, tumors are typically benign and remain confined within the normal boundaries of a tissue. As tumors grow and become malignant, however, they gain the ability to break through these boundaries and invade adjoining tissues.

A schematic outlines alternative pathways cancerous cells can follow after being disseminated to a new tissue during metastasis. Schematics of cancerous cell populations are shown beside descriptive text for each stage. Labeled illustrations are connected with arrows to outline pathways. Vertical dashed or dotted arrows on the left side of the diagram indicate approximate lengths of time for various steps within the diagram.

View Full-Size Image Figure 3 Figure Detail Invasive cancer cells often secrete proteases that enable them to degrade the extracellular matrix at a tissue's boundary. Proteases also give cancer cells the ability to create new passageways in tissues. For example, they can break down the junctions that join cells together, thereby gaining access to new territories.

Metastasis — literally meaning "new place" — is one of the terminal stages of cancer. In this stage, cancerous cells enter the bloodstream or the lymphatic system and travel to a new location in the body, where they begin to divide and lay the foundation for secondary tumors. Not all cancer cells can metastasize. In order to spread in this way, the cells must have the ability to penetrate the normal barriers of the body so that they can both enter and exit the blood or lymph vessels. Even traveling metastatic cancer cells face challenges when trying to grow in new areas (Figure 3).

Conclusion
Cancer is unchecked cell growth. Mutations in genes can cause cancer by accelerating cell division rates or inhibiting normal controls on the system, such as cell cycle arrest or programmed cell death. As a mass of cancerous cells grows, it can develop into a tumor. Cancer cells can also invade neighboring tissues and sometimes even break off and travel to other parts of the body, leading to the formation of new tumors at those sites."
eBooks
This page appears in the following eBook
Essentials of Cell Biology, Unit 5.5
http://www.nature.com/scitable/topicpage/cell-division-and-cancer-14046590

[DrChuck]

I'm not sure what Flip is talking about, but most eukaryotic (non-bacterial) DNA is so-called "junk" DNA which doesn't code for anything, so, yes, mutations in this DNA will not affect the cell.