Loading
Immune checkpoints are brakes on immune cells that tumours press and checkpoint inhibitors release. Cell-cycle checkpoints are gates inside every dividing cell that stop it copying or splitting damaged DNA. They share a word and nothing else, so OnCo keeps a hub for each: every member, its partner, where it is expressed, the drugs against it by class and the approvals by cancer.
Immune cells carry brakes so they do not attack the body. A tumour borrows those brakes: it shows PD-L1 to PD-1 on a T cell, CD47 to a macrophage, HLA-E to an NK cell, and the attack stops. Checkpoint inhibitors are antibodies that block one pair; agonists press the accelerators instead; newer drugs go after the enzymes and secreted signals that quieten the whole neighbourhood.
Brakes carried by the immune cell itself. When the receptor meets its ligand on a tumour cell or an antigen-presenting cell, the T cell or NK cell stands down. Antibodies that block the receptor release the brake.
The other half of each pair. Tumours borrow these molecules from normal tissue so that the brakes on nearby T cells are pressed. Blocking the ligand works as well as blocking the receptor for PD-1.
Signals a cell shows to macrophages to say it is self and should not be eaten. Tumours over-express them; blocking the pair lets macrophages engulf the cancer cell.
Accelerators rather than brakes. These receptors tell a T cell, or the dendritic cell that primes it, to go harder; the drugs are agonists that press them, or bispecifics that press them only where the other arm has found the tumour.
Enzymes and receptors that change the chemistry around the tumour: they use up tryptophan or turn spilt ATP into adenosine, and either change starves or sedates T cells.
Relatives of PD-L1 and CD80 whose receptors are only partly known. Because tumours over-express them, most drugs treat them as an address for an antibody-drug conjugate rather than as a brake to release.
Not receptors but secreted signals that quieten immune cells across a whole tumour. The cited review frames them as immunosuppressive cytokines rather than checkpoints in the strict sense; they are listed here because the drugs against TGF-beta are fused to checkpoint antibodies.
Every cell that divides passes gates: one before it copies its DNA, one before it splits, one inside the split itself, and a damage-response crew behind all three. Cancers break gates to keep dividing, then depend on the ones left. CDK4/6 inhibitors hold the first gate shut; WEE1, ATR, PARP, Aurora and MPS1 inhibitors force a gate open so the cell divides into death.
The first gate. Cyclin D and CDK4/6 phosphorylate RB, which lets the cell commit to copying its DNA; p16 holds CDK4/6 back. Hormone-driven breast cancers lean on this gate, which is why CDK4/6 inhibitors work there.
The second gate, held shut by ATR, CHK1 and WEE1 until copied DNA is checked. Tumours that have lost p53 cannot stop at the first gate, so they rely on this one; drugs that force it open push them into a lethal mitosis.
The sensors and repair crews behind both gates. ATM and ATR detect breaks and stalled forks, CHK1 and CHK2 relay the alarm, p53 decides between pause, repair and death, and PARP patches single-strand breaks. Cancers that have lost one route depend on the others.
The last gate, inside mitosis. MPS1, BUB1 and Aurora B keep the cell from pulling its chromosomes apart until every one is attached; Aurora A and PLK1 build the spindle. Taxanes and vinca alkaloids kill by holding this gate shut for good.
The words around it tell you. Each phrase below opens the family it belongs to.
Machine-readable: checkpoints.json lists both families with their classes and members; each hub has its own data.json with every row.