❌ is the result of an accumulation of key ❌ in ❌ genes in a cell’s progeny, which eventually causes seriously ❌ cell growth and survival. Exposure to environmental ❌, failure of DNA ❌ and ❌ contribute to the accumulation of ❌.

Genes whose mutated version leads to ❌ in the protein product’s activity or in its expression in tumours (usually caused by a ❌ mutation) are called ❌. In contrast, those genes whose products are ❌ in tumours (either affecting their activity or expression), usually by ❌ mutations, are called ❌ genes.

The initial ❌ occurs within a normal cell, leading to the clinical development of a ❌. This progresses with further mutations to ❌, through to fully ❌, which is ❌ and has ❌. Although ❌ in origin, tumours acquire ❌ and contain ❌.

In medical terms, tumours are traditionally classified according to their ❌. The majority of cancers in humans are ❌, from epithelial cells. This is because they have a ❌, which increases the likelihood of mutations occurring. Moreover, they are often exposed to chemical and physical ❌, as they are the first barrier that environmental agents encounter in the body. ❌ are common sites for tumours for this reason.
Other types of cancers are ❌, from muscle or connective tissue, or ❌, from haemopoietic cells.

The key ❌ properties that cells acquire through successive rounds of mutation include: ❌, self-sufficiency in growth signals (usually by activating ❌), insensitivity to growth-inhibitory signals (often involving inactivation of ❌), avoidance of ❌ and replicative ❌, sustained ❌, and tissue invasion and ❌.

Genetic ❌ accelerates the rate of accumulation of key mutations in ❌ genes.
Genetic instability can be a result of ❌ in any of the many genes whose products check, detect and repair ❌ DNA.
Cancer cells show ❌ mutation rates compared to normal cells, due to genetic instability.

The type of genetic ❌ within a cell reflects the ❌ that has been disrupted, e.g. loss of ❌ leads to a superficially ❌, with many ❌ and short repeats, while loss of ❌ leads to ❌ resulting from ❌.

The ❌ protein normally triggers ❌ in response to ❌, leading to DNA ❌ or ❌ if damage is severe. Continued ❌ in p53-deficient cells leads to increasing ❌ and ❌ instability.
50% of ❌ have mutations in the p53 gene.

❌ and ❌ drugs rely on ❌ the DNA of ❌ so severely that they undergo ❌ and die, whilst normal cells, with normal ❌, either undergo ❌ or ❌ and survive.

❌ can be identified by their ability to transform ❌ cell lines and have often been discovered in ❌. Only a ❌ needs to be mutated, because the effect is ❌. ❌ mutations, ❌, amplification and chromosome and gene ❌ can all produce ❌ effects.

Self-sufficiency in ❌ can arise through ❌ of individual components of a ❌ pathway. Proteins encoded by ❌ include ❌ (e.g. PDGF), ❌ (EGF receptors), cytoplasmic ❌ (Ras, Src and Bcr–Abl), and ❌ factors (Myc).

❌, such as ❌ , were originally discovered through study of rare ❌ cancers. For cell tumorigenesis to occur, ❌ need to be inactivated (e.g. by point ❌, deletion, ❌), which is ❌ to occur than activation of a ❌, but has very ❌ on the cell.

Loss of ❌ can cause ❌ to either ❌ signals, or to ❌. Loss of ❌ causes deregulation of the ❌. Loss of ❌ allows cells with sustained ❌ to continue to ❌, when normally they would be ❌ at entry into ❌, by p53/p21CIP-mediated mechanisms, until the damage was ❌.

❌ of the pathways of ❌ is as important in the microevolution of ❌ as the changes that increase the rate of cell ❌. Tumour cells acquire mutations that cause them to resist ❌ by either ❌ pro-apoptotic signals or ❌ anti-apoptotic pathways. Both ❌ and extrinsic pathways can be ❌ in tumorigenic cells.

Tumour cells acquire mutations that cause them to avoid ❌.
One mechanism involves ❌, so that cells with damaged ❌ continue to divide. Tumour cells may also reactivate ❌, often after significant ❌ damage has been sustained, thus allowing clonal tumour cells that would otherwise be ❌, to survive and proliferate.

Most cells suffering from ❌ will synthesize and secrete ❌ (VEGF) which promotes ❌ by attracting ❌ which then form new ❌.
Tumour cells in solid tumours do this too.

Solid ❌ secrete ❌ and other ❌ factors which induce ❌.

Tissue ❌ by tumours requires the breakdown of normal ❌ and cell–cell ❌ interactions; for example, ❌ is absent in some tumours.

❌ is very inefficient and poorly understood. The cells need to break through the ❌ of blood or lymphatic vessels, probably aided by the secretion of serine proteases or ❌. Once in the circulation, they lodge in ❌ (or if in lymphatics, lodge in draining lymph nodes) and may then colonize the new tissue. Successful ❌ probably depends on the degree of ❌ of the ❌ cells.

Colorectal cancer is a suitable model for the study of ❌, due to the availability of surgically removed early polyps. There are characteristic ❌, some relating to the ❌, and some tending to occur ❌ or later in the progression.

Mutations in the Wnt pathway genes ( APC and β -catenin ), which maintain ❌, are common in human colorectal cancer; ❌ are found in patients with familial adenomatous polyposis coli.

Mutations of ❌ are particularly common in human colorectal cancer, while mutations in genes encoding proteins of the ❌ ( Smad4, TGFrII ), in DNA ❌ repair genes and in ❌ genes are found at lower frequencies.

❌ is involved in activation of the ❌ checkpoint in response to ❌, which leads to cell cycle ❌. It also acts as an inducer of downstream pathways of ❌ and (if repair is unsuccessful) ❌, and is involved in the induction of ❌