The scienceMetastatic cancer (cancer that has spread)

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The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models.

The science

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Targets

The targets of this cancer's medicines and the ones linked to it directly.

ALK BRAF CDK4/6 HER2 MEK1/2 NTRK PD-1 RANK ligand (RANKL)RET ROS1

How often this target appears

Target / alteration	Prevalence	Measure
5-HT3 receptor (HTR3A)	host%	Host target: serotonin receptor on gut vagal endings and the vomiting centre. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
Adenosine deaminase (ADA)	all%	Housekeeping enzyme present in every dividing cell (purine breakdown, highest in lymphocytes); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Cannabinoid receptor 1	host%	Host target: brain cannabinoid receptor. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
CD3	immune%	Immune-cell target (CD3 on every T cell, the arm that T-cell engagers pull on): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers.
CD73 / adenosine axis	immune%	Immune-cell target (CD73 and adenosine on tumour and immune cells; tumour expression varies and is measured in trials): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers.
CRAF (RAF1)	all%	Signalling protein present in most cells (CRAF in the RAS-MAPK relay); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
Dihydrofolate reductase (DHFR)	all%	Housekeeping enzyme present in every dividing cell (folate recycling); not a selection marker, which is why these drugs are given by cancer type rather than by test.
DNA polymerase alpha (POLA1)	all%	Housekeeping enzyme present in every dividing cell (DNA strand initiation); not a selection marker, which is why these drugs are given by cancer type rather than by test.
DNMT1 (DNA methyltransferase 1)	all%	Housekeeping enzyme present in every dividing cell (methylation maintenance during replication); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Dopamine D2 receptor	host%	Host target: dopamine receptor; also the target in prolactin-secreting pituitary tumours. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
Elongation factor 2 (EEF2)	all%	Housekeeping enzyme present in every dividing cell (protein synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test.
EphA2 receptor	all%	Signalling protein present in most cells (EphA2 receptor, over-expressed in many solid tumours without a selecting mutation); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
Erythropoietin receptor (EPOR)	host%	Host target: erythropoietin receptor on marrow red-cell precursors. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
FKBP12 (FKBP1A)	all%	Housekeeping enzyme present in every dividing cell (rapamycin-binding protein); not a selection marker, which is why these drugs are given by cancer type rather than by test.
FRK kinase	all%	Signalling protein present in most cells (FRK kinase); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
GART (trifunctional purine synthesis enzyme)	all%	Housekeeping enzyme present in every dividing cell (purine synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Glutathione reductase	all%	Housekeeping enzyme present in every dividing cell (antioxidant recycling); not a selection marker, which is why these drugs are given by cancer type rather than by test.
GM-CSF receptor (CSF2RA)	host%	Host target: GM-CSF receptor on white-cell precursors. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
HCK kinase	all%	Signalling protein present in most cells (HCK kinase, mainly in white blood cells); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
IGF-1 receptor (IGF1R)	all%	Signalling protein present in most cells (IGF-1 receptor, widely expressed; a decade of trials found no selecting marker); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
IL-11 receptor alpha	host%	Host target: IL-11 receptor on platelet precursors. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
Interferon alpha receptor (IFNAR1)	immune%	Immune-cell target (interferon alpha receptor on immune and tumour cells alike): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers.
LYN kinase	all%	Signalling protein present in most cells (LYN kinase under the B-cell receptor); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
Mu-opioid receptor	host%	Host target: mu-opioid receptor in pain pathways and gut. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
NK1 receptor (TACR1)	host%	Host target: substance P receptor in the vomiting pathway. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.
Proteasome (PSMB5)	all%	Housekeeping enzyme present in every dividing cell (protein disposal, on which myeloma cells depend most); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Protein kinase C family (PKC)	all%	Signalling protein present in most cells (protein kinase C family); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
PTK6 (BRK)	all%	Signalling protein present in most cells (PTK6, over-expressed in many breast cancers without a selecting mutation); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
Retinoid X receptor (RXR)	all%	Signalling protein present in most cells (retinoid X receptor); bexarotene acts on the pathway rather than on a mutation that selects patients, so no prevalence applies.
Ribonucleotide reductase (RRM1)	all%	Housekeeping enzyme present in every dividing cell (DNA building-block synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test.
RON receptor (MST1R)	all%	Signalling protein present in most cells (RON receptor kinase, a secondary target of MET drugs); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
SRC family kinases	all%	Signalling protein present in most cells (SRC family kinases); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
Thioredoxin reductase 1	all%	Housekeeping enzyme present in every dividing cell (antioxidant recycling); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Thymidylate synthase (TYMS)	all%	Housekeeping enzyme present in every dividing cell (thymidine synthesis); not a selection marker, which is why these drugs are given by cancer type rather than by test.
TIE2 receptor (TEK)	all%	Signalling protein present in most cells (TIE2 on blood-vessel endothelium); drugs act on the pathway rather than on a mutation that selects patients, so no prevalence applies.
TIM-3	immune%	Immune-cell target (TIM-3 checkpoint on exhausted T cells and myeloid cells): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers.
Toll-like receptor 7 (TLR7)	immune%	Immune-cell target (innate immune sensor in skin and immune cells, switched on by imiquimod): expressed on immune cells rather than on the tumour, so patient selection rests on the cancer type and, in trials, on PD-L1 or immune biomarkers.
Topoisomerase I (TOP1)	all%	Housekeeping enzyme present in every dividing cell (DNA unwinding during replication); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Tubulin (microtubules)	all%	Housekeeping enzyme present in every dividing cell (microtubule scaffold for cell division); not a selection marker, which is why these drugs are given by cancer type rather than by test.
Xanthine oxidase (XDH)	host%	Host target: xanthine oxidase in uric acid formation. Not a tumour alteration, so no prevalence applies; the drug acts on normal tissue or on symptoms.

How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.

Model panel1 model

Machine commentary by named AI models on a date, not clinical review. Claims are tied to the record's own sources; check them before relying on anything here.

FableAnthropic · v5.12026-09-17medium confidence

The record's core definitions are well supported by its two sources: metastatic cancer keeps the name of the primary, spreads most commonly to bone, liver, lung and brain, is responsible for most cancer deaths, and the Paget seed and soil history is correctly dated. The more specific clinical content, including the SABR-COMET five-year survival figures, the list of tissue-agnostic approvals and the early palliative care trial, is not covered by either the NCI page or the Wikipedia article and rests on linked OnCo records instead, so it cannot be verified from the sources given. The record would benefit from distinguishing regional lymph node spread from distant metastasis, from clarifying that 'advanced cancer' is not strictly synonymous with metastatic disease, and from citing the SABR-COMET history entries consistently. Nothing in the two sources contradicts the record.

Right 4Missing 1Unclear 3Show verdicts

Right
It keeps the name of where it started, and a breast cancer that has spread to the liver is still breast cancer treated with breast cancer drugs.
The NCI page states that metastatic cancer has the same name and the same type of cancer cells as the original cancer, and that treatment is generally based on the primary type.
NCI: Metastatic cancer
Right
Metastatic cancer spreads most often to the bones, liver, lungs or brain.
The NCI page lists common sites of metastasis by primary cancer, and bone, liver, lung and brain recur across most of the listed primaries. The record's own caveat that the pattern depends on the primary site matches that presentation.
NCI: Metastatic cancer
Right
Most cancer deaths follow metastasis rather than growth of the original tumour.
The Wikipedia article on metastasis describes metastatic spread as the main cause of cancer mortality, consistent with the record's burden statement. The record does not give a figure, so nothing here needs checking against a number.
Wikipedia
Right
In 1889 Stephen Paget proposed the seed and soil hypothesis, that cancers spread to organs whose environment suits them.
The Wikipedia article covers Paget's seed and soil hypothesis and dates it to 1889. This history entry has no refs in the record, so the Wikipedia link is its only support.
Wikipedia
Unclear
In SABR-COMET, adding stereotactic radiotherapy to every metastasis raised five-year overall survival from 17.7 to 42.3 percent.
Neither listed source reports SABR-COMET or its survival figures, so the numbers cannot be checked from the record's own citations. The linked trial record 'sabr-comet' describes the result only qualitatively. Note also that the 2019 history entry for SABR-COMET refs 'sbrt' rather than 'sabr-comet', while the 2020 entry refs 'sabr-comet'; the two entries would be easier to match if they cited the same record.
Wikipedia
Unclear
Pembrolizumab (2017), larotrectinib, entrectinib, dabrafenib with trametinib, selpercatinib and trastuzumab deruxtecan are approved regardless of where the cancer began.
Neither the NCI page nor the Wikipedia article addresses tissue-agnostic drug approvals, so this list and the 2017 date rest on the linked drug records rather than on the record's cited sources. The linked pembrolizumab, larotrectinib and selpercatinib records are consistent with the record's wording, but they are not among the citable sources here.
NCI: Metastatic cancer
Unclear
Aliases include 'Advanced cancer', 'Stage 4 cancer' and 'Stage IV cancer'.
The NCI page equates metastatic cancer with stage IV for most solid tumours, which supports the stage IV aliases. 'Advanced cancer' is broader in common usage and can include locally advanced disease that has not spread to distant sites; the record's sources do not settle whether it should be treated as a straight synonym, and the record could say so.
NCI: Metastatic cancer
Missing
Metastasis is the process by which cancer cells leave the original tumour, travel through blood or lymph and grow in another organ.
Both sources distinguish spread to nearby lymph nodes (regional) from spread to distant organs (distant metastasis), and the NCI page explains that only the latter is usually called metastatic or stage IV. The record describes the process but does not make this distinction, which matters for how the aliases and the 'burden' statement are read.
NCI: Metastatic cancer

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ProvenanceLast edited 2026-09-17 · Jude Gomila · Reverse links for orphaned trials · diff · file

Wikipedia

Metastasis

Sources & links

NCI: Metastatic cancer