The gene GSK3β, which encodes glycogen synthase kinase 3 (GSK3), was originally identified in 1980.

This is a serine/threonine kinase, and is highly conserved, from yeast to mammals. Deletion of GSK3β leads to embryonic lethality at E16 caused by hepatocyte apoptosis. This shows that the functions of GSK3β are not compensated by the presence of GSK3α.

In cancer cell lines, GSK3β modulation, particularly using pharmacological inhibitors, decreases cell proliferation and survival, and induction of apoptosis.

PTEN is a tumor suppressor gene that encodes a dual-specificity phosphatase with both protein phosphatase and lipid phosphatase activity. This lipid phosphatase activity is critical for its tumor suppressor function. The complete loss of PTEN is extremely common in tumor cell lines. PTEN loss of function is observed in many types of cancer including breast, prostate, and endometrial cancer. Around 5-14% of colorectal cancers show PTEN mutations.

Mitogen-activated protein (MAP) kinase kinase (MAP2K) belong to a family of serine/threonine kinase also known as MEKs or MKKs. The genome encodes seven members that regulate the activity of downstream MAP kinases .The MAP kinase pathway is among the most frequently deregulated in human cancer. Even though the frequency of mutation of MAP2K is around 1% upstream activators such as Raf or Ras are mutated in respectively 20% and 30% of all human cancers.

DNA can be damaged through environmental attacks such as tobacco smoke or UV light, or through error introduced as part of the normal DNA replication processes. These can cause up to one million changes to the DNA each day. These changes to the DNA, and therefore any resulting proteins, increase the risk of cancer. To maintain the integrity and stability of the DNA, the cell has its own in-built DNA repair mechanisms that correct the errors, by chemically reversing the damage, or by removing and replacing the damaged bases.

The division cycle in eukaryotic cells can be divided into four phases: cell growth and protein/mRNA synthesis (G1 phase); DNA replication (S phase); cell growth and protein synthesis (G2 phase); and mitosis (separation of the chromosomes) and cell division (M phase). There are checkpoints between the phases (G1/S checkpoint and G2/M checkpoint). The cell can only progress to the next phase after phase processes and DNA repair are verified. If the phases of the cell cycle become dysregulated, this can lead to uncontrolled cell replication and tumor formation.

RAS genes are the most common targets for somatic gain-of-function mutations in human cancer and belong to a class of genes known as oncogenes. When mutated, oncogenes have the potential to cause normal cells to become cancerous. In its active form KRAS is able to activate downstream proteins including the PI3K-AKT-mTOR pathway, which is involved in cell survival, and the RAS-RAF-MEK-ERK pathway, which is involved in cell proliferation. KRAS mutations have been found in bladder, ovarian, thyroid, lung, colorectal and pancreatic carcinoma; neuroblastoma; rhabdomyosarcoma; and acute nonlymphocytic leukemia.

MSH2 is a component of the MMR system. It is responsible for the post-replicative repair of mismatches and small single-stranded DNA loops, and it is critically involved in preventing recombination between homologous DNA sequences. The MSH2 protein was identified as a locus frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). HNPCC is the most common hereditary variant of colorectal cancer (CRC), which accounts for 2-5% of CRCs, mainly due to hMLH1 and hMSH2 mutations that impair DNA repair functions.

Transforming growth factor beta receptor type II (TGFBRII) is a putative tumor suppressor gene which belongs to the serine-threonine kinase family. These are multifunctional peptides that regulate proliferation, differentiation, adhesion, migration, and other functions in many cell types by transducing their signal through combinations of transmembrane type I and type II receptors (TGFBRI and TGFBRII) and their downstream effectors, the SMAD proteins.
TGFBRII is part of the transforming growth factor–ß (TGF-ß) signaling pathway. The TGF-ß signaling pathway is involved in many cellular processes in both the adult organism and the developing embryo including cell growth, cell differentiation, apoptosis, cellular homeostasis and other cellular functions.
Deregulation of this pathway appears to play an important role in colon carcinogenesis by affecting TGF-β-mediated growth inhibition, apoptosis, and differentiation as well as other TGF-β-regulated processes
The mutational inactivation of TGFBRII occurs in approximately 30% of colon cancers and promotes the formation of colon cancer by inhibiting the tumor suppressor activity of the TGFB signaling pathway.

SMADs are highly conserved across species, especially in the N terminal MH1 domain and the C terminal MH2 domain. Activation of the canonical TGF-β signaling pathway provides growth inhibitory signals in the normal intestinal epithelium. Mutations SMAD4 and SMAD2 have been identified in human cancers and more importantly with high frequency in pancreatic and colorectal cancer.

CTNNB1 is a gene that encodes the dual-function protein β-catenin in humans. β-catenin plays a role in cell-cell adhesion and cell signaling as an essential part of the WNT signaling pathway. It is part of a complex of proteins that constitute adherens junctions. β-catenin dependent WNT signaling pathways have crucial roles in the regulation of diverse cell behaviors, including cell fate, proliferation, survival, differentiation, migration, and polarity.