PD-1 binds to its ligand PD-1L and leads to T cell activation

PD-1 binds to its ligand CTLA4 and leads to T cell activation

PD-1 binds to its ligand PD-L1 and induces T cell division and expansion

The PD-1/PD-1L interaction leads to downregulation of the PI3-K / m-TOR/ RAS/Ras/MAPK/Erk pathways and T cell exhaustion 

Antibodies in which the majority of the sequence is of human origin except for the complementarity determining regions (CDR), which are mouse sequence

Antibodies in which the entire constant and variable regions are human sequence

Antibodies in which the entire constant and variable regions are mouse sequence

Fab fragments that are entirely of human sequence

Host immune response

Inability to recognise and bind the native antigen

Antibody dependent cytotoxicity 

Antibody degradation

Increased expression of other tyrosine kinases

The Bcr-Abl threonine residue in the kinase domain is mutated to an isoleucine (T315I) which blocks Glivec access to Bcr-Abl

Amplification of Bcr-Abl

Altered expression of drug transporter proteins

an increase in Purkinje cell number

reduced differentiation of granule cell precursors in the internal granular layer (IGL)

abnormal architecture of the Bergmann glial cells

an expansion of the granule cell precursors in the internal granular layer (IGL)

Patched is a positive regulator of hedgehog pathway signalling

The cilia is not required for regulation of the hedgehog signalling pathway

Smoothened (Smo) is an inhibitor of the Hedgehog signalling pathway

The introduction of the Smoothened mutation SmoM2 in a mouse model is able to induce medulloblastoma and basal cell carcinoma

highly sensitive to UV-light induced DNA damage due to gain of function mutations

at an increased risk of basal cell carcinoma due to loss of function mutations in the PTCH gene

at an increased risk of basal cell carcinoma due to gain of function mutations in the PTCH gene

at an increased risk of basal cell carcinoma due to reduced Hedgehog signalling

Vemurafenib, dabrafenib and trametinib are reversible inhibitors of the kinase domain of B-RAF

Vemurafenib blocks MAPK signalling by wild-type B-RAF, B-RAF(V600E) mutant and p61 B-RAF (V600E) mutant to induce cell cycle arrest and apoptosis of melanocytes

Vemurafenib blocks MAPK signalling by B-RAF(V600E) mutant, to induce cell cycle arrest and apoptosis of melanocytes

Vemurafenib, dabrafenib and trametinib are non-competitive inhibitors of the kinase domain of B-RAF

CACCAG

GCAACC

GCAATC

CACCAA

Malignant melanoma, Basal cell carcinoma, Squamous cell carcinoma

Squamous cell carcinoma, Basal cell carcinoma, Malignant melanoma

Basal cell carcinoma, Squamous cell carcinoma, Malignant melanoma

Malignant melanoma, Squamous cell carcinoma, Basal cell carcinoma