Cancer Drug Simulator · Phases 1–2

One cancer, two drugs — watch them work, or watch them fail.

The simulator covers one cancer — chronic myeloid leukaemia (CML) — and the drugs aimed at it. Phase 1: imatinib (Gleevec), the drug that turned CML into a manageable disease. Phase 2 adds dasatinib (Sprycel), the second-generation drug built to work where imatinib fails. Follow either drug from a swallowed tablet to the moment a leukaemia cell dies.

Educational simulation only. This page explains how these drugs work, based on the sources listed at the bottom. It is not medical advice, and nothing here is a recommendation to take, stop, or switch any medicine.

Disclaimer: All content on this site was created by AI based on extensive research on the internet. If you believe any information is not accurate, please email your suggestions to r81138965@gmail.com. There is no guarantee that the website will be updated accordingly, or on a timely basis. See the full disclaimer in the footer below.

STEP 1

Pick the cancer

One cancer, researched in depth, carries both phases. More cancers arrive in later phases, one at a time, each with its own verified drug list. Tap the name to see its details.

STEP 2

Pick the drug

Both drugs in this list were built for CML: imatinib, and dasatinib — the second-generation drug that answers most imatinib resistance. Choose one from the drop-down list to load it into the simulation below. Its details stay hidden until you tap its Details button.

Effective drug for CML

In the simulationChanging the selection loads that drug into Step 3.

STEP 3

Run the simulation

Follow the drug from the mouth to the inside of a CML cell. Use the scene chips to jump around. With imatinib or dasatinib selected, you can also flip the cell to a resistant mutant — T315I, which defeats both drugs — and with dasatinib, to an imatinib-resistant mutant (E255K) that it still kills. How the scenes are drawn: every stage gets its own animation wherever a drug's mechanism at that stage differs — a shared scene means the underlying process there is genuinely the same (apoptosis, for instance, is the cell's own program once its survival signals are gone, whichever drug switched them off).

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Scale note: drug molecules are drawn enormously enlarged. A real imatinib molecule is roughly 1 nm across (an estimate from its size, 493.6 Da), while a cell is about 10,000× wider — at true scale the drug would be invisible. Dasatinib (488.01 Da) is almost exactly the same size, so it is drawn at the same scale: the difference between the two drugs is fit, not size. Cells, by contrast, are drawn close to their real relative sizes.

The target: a switch that won't turn off

CML starts with one acquired accident in a single bone-marrow stem cell. It is not inherited — the fusion gene is not passed to children; it arises in that one cell, whose descendants then crowd out normal blood production.

Normal ABL1 is a tightly regulated enzyme with its own off-switch. The fusion keeps ABL1's kinase but loses the regulation: the BCR portion forces the proteins to pair up and switch each other on, around the clock. Source: NCI PDQ; Jayavel et al. 2025.

What the stuck switch does

Active BCR-ABL constantly tags other proteins with phosphates, holding three circuits open at once:

RAS → MAPK — "divide now" signals to the nucleus
PI3K → AKT → mTOR — the main "stay alive" pathway
STAT5 — a transcription factor driving growth and survival

The result: myeloid cells multiply without waiting for growth-factor permission, refuse to die on schedule, and stick less firmly to the marrow — so immature cells spill into the blood.

What a CML cell actually looks like

Honestly? Like a normal immature white cell. A CML blast is not a different shape or colour from a healthy myeloblast (~15 µm, big pale nucleus, thin rim of light-blue cytoplasm). Pathologists spot CML in the population, not the single cell:

Far too many immature myeloid forms in blood and marrow ("left shift")
Raised eosinophils and basophils; packed, hypercellular marrow
Blasts circulating where they should be rare or absent

That's why the simulation marks the CML cell with its glowing BCR-ABL inside — the real difference is internal and behavioural, not cosmetic.

The three phases, by blast percentage

<10%Blasts · Chronic phase

Often few or no symptoms. Commonest finding is an enlarged spleen; fatigue, weight loss, night sweats and fever can occur. This is where imatinib's 400 mg dose applies, and where most patients are diagnosed.

10–19%Blasts · Accelerated phase

The disease is gaining. Rising white cells and platelets, worsening anaemia, growing spleen, increasing abnormalities and marrow scarring (fibrosis). Imatinib dose rises to 600 mg daily in this phase.

≥20%Blasts · Blast phase / crisis

Now resembles acute leukaemia — about two-thirds myeloid, one-third lymphoid — with fever, malaise and progressive splenomegaly. Untreated, blast crisis is fatal within months.

Terminology note: the three-phase ladder above is the classic teaching scheme (NCI PDQ). The WHO 5th edition (2022) now recognises just two phases — chronic and blast — treating "accelerated" as a transition, because modern kinase inhibitors have made it less prognostically important.

Imatinib, by the numbers

Every figure below is from the current FDA prescribing information for Gleevec (revised July 2026) — no percentages have been rounded into existence anywhere else on this page.

400 mg

Daily dose, chronic phase

600 mg in accelerated/blast phase. Taken with a meal and a large glass of water; tablets are 100 mg and 400 mg.

98%

Reaches the blood

Mean absolute bioavailability after swallowing. Peak blood levels arrive in 2–4 hours.

~95%

Bound to plasma proteins

Mostly albumin and α1-acid glycoprotein. Only the unbound ~5% is free to enter cells.

~18 h

Half-life

Its main active breakdown product lasts ~40 h. Levels build 1.5–2.5× at steady state on once-daily dosing.

CYP3A4

Broken down in the liver

The main circulating metabolite (CGP74588) is also active, at ~15% of the parent drug's exposure.

68% / 13%

Leaves via faeces / urine

About 81% of a labelled dose is eliminated within 7 days, mostly as metabolites.

One honest gap: the FDA label gives no bone-marrow drug concentration, and there is no special "marrow-targeting" step in reality. Blood reaches the marrow through leaky sinusoid capillaries, and the drug simply diffuses out — which is how the simulation shows it.

Phase 2 — dasatinib, by the numbers

Dasatinib (Sprycel, Bristol Myers Squibb) is the second-generation answer to imatinib resistance: FDA-approved in June 2006 for imatinib-resistant or -intolerant CML, and on 28 October 2010 for newly diagnosed chronic-phase CML. Figures below are from the current FDA prescribing information for Sprycel (revised September 2026) unless another source is named.

100 mg

Daily dose, chronic phase

Once daily, swallowed whole, with or without food. 140 mg daily in accelerated/blast phase. Tablets are white to off-white.

325×

More potent than imatinib

Against unmutated BCR-ABL in vitro, with an IC₅₀ under 1 nM. Source: Dove Medical Press review of dasatinib in CML.

~96%

Bound to plasma proteins

Only ~4% is free drug. Peak blood levels arrive 0.5–6 hours after a dose; a high-fat meal raises exposure only ~14%.

3–5 h

Half-life

Short — yet once-daily dosing works. The label does not quantify how long BCR-ABL stays inhibited after blood levels fall, so no duration is claimed here.

CYP3A4

Broken down in the liver

Strong CYP3A4 blockers multiply exposure (ketoconazole: ~5× the AUC); acid reducers cut it sharply (famotidine −61% AUC). Grapefruit juice should be avoided.

85% / 4%

Leaves via faeces / urine

Of a radiolabelled dose within 10 days. Its active breakdown product is only ~5% of exposure and is unlikely to play a major role.

Head-to-head: the DASISION trial

Dasatinib 100 mg vs imatinib 400 mg daily in newly diagnosed chronic-phase CML (n=519), from the FDA label:

Confirmed complete cytogenetic response within 12 months: 76.8% vs 66.2%
Major molecular response at 12 months: 52.1% vs 33.8%
Median time to major molecular response: 9.3 vs 15.0 months
Major molecular response at 60 months: 76.4% vs 64.2%
Progression to accelerated/blast phase at 60 months: 3% vs 6%

What visibly changes vs imatinib

Entry: passive diffusion straight through the membrane — no hOCT1 transporter needed, so low hOCT1 cannot cause dasatinib resistance the way it can imatinib resistance.
Fit: binds BCR-ABL in both its active and inactive shapes; imatinib fits only the inactive one. The label phrases this cautiously — modelling predicts binding to multiple conformations.
Extra targets: SRC-family kinases (SRC, LCK, YES, FYN — and LYN and HCK, which are implicated in imatinib resistance), plus c-KIT, EPHA2 and PDGFRβ.
Same size: 488.01 Da vs imatinib's 493.6 Da — the difference is fit, not size, so the simulation draws the two molecules at the same scale.

One thing science hasn't settled: how imatinib gets into the cell

The simulation shows the molecule crossing the membrane — but it deliberately does not show a doorway, because the literature disagrees about whether one exists. Both sides, fairly stated:

The transporter model (2004)

A widely cited Blood study found imatinib uptake into CML cells was temperature-dependent and blocked by inhibitors of hOCT1, a membrane transporter — concluding that "active transport processes mediate the influx and efflux of imatinib." Efflux by the P-glycoprotein pump (MDR1/ABCB1) was also shown.

Thomas et al., Blood 2004

The diffusion model (2019)

A later study, in oocytes and kidney cells engineered to express OCT1/2/3, found uptake occurred independently of all three transporters at normal pH — best explained by passive diffusion of the small uncharged fraction of the drug across the lipid membrane, falling off as pH drops.

OCT uptake study, 2019

What the sim does with this: imatinib is shown diffusing through the membrane (the later study's model), with no transporter drawn as fact. The efflux pump is on firmer ground — P-glycoprotein really can throw imatinib back out of the cell, and it returns below as a resistance mechanism.

The cost: what imatinib does to healthy cells

Healthy cells have no BCR-ABL — so why any side effects at all? Because imatinib also blocks three look-alike kinases that normal tissues genuinely need: normal ABL, c-KIT, and PDGFR. Each side effect below is traced to the tissue involved. The first set appears in the FDA label's list of most frequent reactions (≥30% of patients); low blood counts and liver effects are separate labelled warnings. Where the mechanism is a best guess rather than established, the tag says so — the label itself often lists the effect without stating a mechanism.

Low blood counts

Bone marrow · blood stem cells

Neutropenia, thrombocytopenia, anaemia. c-KIT sits on the haematopoietic stem cells that rebuild blood, and blocking it "probably contributes to the myelosuppression" — the best-supported explanation. Killing off the leukaemic clone also temporarily removes the marrow's (abnormal) workforce before healthy production recovers. The label advises weekly blood counts for the first month, then biweekly, then periodically.Mechanism: best-supported

Fluid retention & swelling

Tissues · eyelids, ankles, lungs

Oedema — classically puffy eyelids in the morning and swollen ankles; in severe cases fluid around the lungs or heart, or in the abdomen. PDGFR helps regulate fluid pressure in tissues, so blocking it is thought to let fluid leak out of capillaries — but the FDA label lists this as a warning without stating a mechanism.Mechanism: probable, not label-stated

Nausea, vomiting, diarrhoea

Gut · interstitial cells of Cajal

The gut's pacemaker cells — the interstitial cells of Cajal, which drive intestinal movement — are rich in c-KIT, and blocking it is the leading explanation for diarrhoea. Nausea also has a simpler contributor: the drug is swallowed, and some leaves the body unchanged in the faeces, irritating the gut on the way through.Mechanism: plausible (review-supported)

Muscle cramps & aches

Skeletal muscle · calves, feet, hands

Often at night. PDGFR inhibition in muscle cells "most likely contributes" to the musculoskeletal pain. For the cramps themselves, the honest answer is that the exact mechanism is not fully understood — changes in calcium/magnesium handling after kinase inhibition have been proposed.Mechanism: not fully elucidated

Liver strain

Liver · hepatocytes

Raised liver enzymes and bilirubin; rarely, severe liver injury. Imatinib is processed in the liver by CYP3A4, and the label warns that "severe hepatotoxicity, including fatalities may occur," advising liver tests before starting and monthly after. How the drug injures liver cells is not established — no mechanism is invented here.Mechanism: not established

Skin rash

Skin · basal cells, melanocytes, mast cells

c-KIT is expressed on skin basal cells, pigment-making melanocytes and mast cells, and its inhibition "may have a role" in rash; loss of skin pigmentation has also been reported. Rarely, severe blistering reactions (including Stevens–Johnson syndrome) occur — a labelled warning.Mechanism: may contribute

Also among the label's ≥30% reactions: fatigue and headache — systemic effects with no single cell type to pin them on. Other labelled warnings (mention only): heart failure in susceptible patients, bleeding, gut perforation, kidney effects, and slowed growth in children.

Dasatinib's cost: a different set of side effects

The broader kinase blockade that makes dasatinib stronger also changes its side-effect profile — its signature problem, fluid around the lungs, barely occurs with imatinib, while imatinib's puffy-eyelid swelling is less common. Rates are from the DASISION trial as reported in the FDA Sprycel label (60-month follow-up, all grades, dasatinib vs imatinib). Where the mechanism is not established, the tag says so.

Fluid around the lungs

Pleura · chest capillaries, lymph drainage

Pleural effusion — dasatinib's signature side effect: 28% of patients vs 1% on imatinib (severe grade 3/4: 3% vs 0%). The leading idea is that blocking SRC-family kinases and PDGFRβ — both involved in keeping blood-vessel walls sealed — makes pleural capillaries leak fluid faster than it drains. But sources state plainly that the exact mechanism is not established.Mechanism: not established

Low blood counts

Bone marrow · blood progenitors

Myelosuppression — thrombocytopenia, neutropenia, anaemia — is among dasatinib's most common reactions, and severe cases come earlier and more often in advanced-phase disease. Normal marrow progenitors depend on c-KIT and SRC-family kinases, both of which dasatinib blocks; exactly how the blame splits between those targets and the disease itself is not proven.Mechanism: plausible, not proven

Bleeding

Platelets · blood-vessel walls

Haemorrhage in 8% of patients (the same rate as imatinib in DASISION); severe bleeding, including rare brain haemorrhage, is a labelled warning. SRC-family kinases help platelets activate and clump, so dasatinib plausibly impairs platelet function on top of lowering platelet counts — a well-supported mechanism, though the label lists the risk without assigning one.Mechanism: plausible (attributed)

Fluid retention

Tissues · heart sac, body-wide capillaries

Fluid retention overall: 38% vs 45% on imatinib — but the pattern differs. Dasatinib causes less surface swelling (14% vs 38%) and more fluid where it matters more: around the lungs (above) and around the heart (pericardial effusion 4% vs 1%). The same leaky-capillary hypothesis is offered as for pleural effusion, and it is equally unproven.Mechanism: not established

High pressure in the lung arteries

Pulmonary arteries · vessel lining and muscle

Pulmonary arterial hypertension is rare — about 0.45% of patients in the literature — but serious. It can appear more than a year into treatment, may reverse when the drug is stopped, and if confirmed, dasatinib must be stopped permanently. The proposed mechanism (SRC/PDGFR blockade disturbing the vessel lining and remodelling the artery wall) is unproven.Mechanism: unclear

The everyday list

Gut · skin · systemic

Diarrhoea 22% (vs 23% on imatinib), rash 14% (vs 18%), headache 14% (vs 11%), fatigue 11% (vs 12%), muscle and joint pain 14% (vs 17%), nausea 10% (vs 25% — notably less than imatinib). No established mechanism was found for these; they are common across this drug class. Other labelled warnings (mention only): heart-ischaemia events (3.9% vs 1.6% at 5 years), QT prolongation (<1%), liver effects, and slowed growth in children.Mechanism: unclear

How CML fights back: resistance

Run the T315I variant in the simulation above to see the most famous escape in action. Resistance comes in two families — changes to BCR-ABL itself, and workarounds that don't involve it.

Changing the target

Kinase-domain mutations — the commonest mechanism. Over 90 have been catalogued. Many work by reshaping the pocket or favouring the active fold imatinib can't bind — while ATP still fits perfectly.
T315I, the "gatekeeper": threonine 315 sits at the mouth of the ATP pocket. Swapping it for bulkier isoleucine both physically blocks imatinib (and dasatinib, nilotinib, bosutinib) and removes a hydrogen bond the drug relies on. ATP is unaffected.
Others to know: P-loop mutations G250E, Y253F/H and E255K/V destabilise the inactive shape imatinib needs; F317L also reduces binding.
Amplification: extra copies of the BCR::ABL1 gene make more oncoprotein than the standard dose can keep up with.

Bypassing the target

Efflux pumps: overproduced P-glycoprotein (ABCB1) and ABCG2 throw imatinib out of the cell faster than it accumulates.
Alternative wiring: the cell re-routes survival through SRC-family kinases (e.g. LYN), or re-lights RAF/MEK/ERK, PI3K/AKT and JAK/STAT — so it survives even with BCR-ABL off.
Drug exposure: poor absorption, or other medicines that speed up CYP3A4, lower the dose the cell ever sees.
Quiescent stem cells: dormant leukaemic stem cells can sit out treatment despite BCR-ABL inhibition, and clonal evolution adds further chromosomal damage over time.

Phase 2 update — what dasatinib rescues, and what beats it too

Dasatinib still kills CML cells carrying most imatinib-resistant mutations — including the P-loop mutations Y253H and E255K/V and F359V/C/I, plus M244V, G250E and M351T — which is why it is the standard second-line choice after imatinib failure. Try the E255K variant in the simulation above. But several changes defeat dasatinib itself:

T315I — the gatekeeper; resistant to imatinib and to every second-generation drug. Only ponatinib and asciminib are active against it.
F317L (and F317V/I/C) — residue 317 sits in the drug-binding pocket; swapping it weakens dasatinib's grip.
V299L — also in the pocket region; it rarely appears on imatinib and typically emerges on dasatinib itself. T315A is likewise highly dasatinib-resistant.

Dasatinib can also be pumped back out of the cell — it is a substrate of the ABCB1, ABCG2 and ABCC6 efflux pumps — though how much that matters in patients is uncertain, and quiescent leukaemic stem cells can survive any of these drugs. Sources: ELN 2025 recommended-TKI table; FDA Sprycel label §12.1/§12.3.

Waiting in the wings: later phases

Two newer drugs matter most for where this simulator goes next — above all because they answer the T315I problem in two completely different ways. They are researched and summarised here, but not yet simulated: each gets its own phase, and your testing decides when.

Allosteric inhibitor · PillLater phase

Asciminib

Scemblix · the STAMP inhibitor

Doesn't touch the ATP pocket at all. Normal ABL1 switches itself off by tucking a fatty tag (a myristoyl group) into a side pocket — BCR-ABL lost that tag, which is part of why it's stuck on. Asciminib occupies that empty myristoyl pocket and restores the off position from the side. Because T315I only changes the ATP pocket, asciminib still works against it (at higher doses).

FDA approval: Oct 2021 (pre-treated / T315I)
Newly diagnosed CML: Accelerated approval, 29 Oct 2024

3rd-gen kinase inhibitor · PillPhase 3 candidate

Ponatinib

Iclusig · built to fit T315I

Still an ATP-pocket drug — but engineered to thread past the bulky isoleucine that blocks imatinib, so it inhibits both normal and T315I BCR-ABL. The trade-off is serious: it carries a boxed warning for arterial blockages, blood clots, heart failure and liver toxicity, which is why it's reserved for resistant disease despite its power.

FDA approval: Dec 2012 (resistant / T315I CML)
T315I coverage: Yes — with asciminib, the only two

Also on the roadmap: the other second-generation ATP-pocket drugs — nilotinib, an imatinib derivative ~30× more potent that, like imatinib, binds only the inactive shape and fails against T315I and against Y253H, E255K/V and F359V/C/I (where dasatinib is preferred); and bosutinib, a dual SRC/ABL inhibitor that binds the active shape like dasatinib but fails against T315I and V299L and is dominated by gut side effects — plus olverembatinib, a third-generation drug approved in China but not by the FDA or EMA as of the 2025 review literature. Investigational allosteric inhibitors (e.g. TERN-701, ELVN-001) are in early trials.

Sources

Researched 8 November 2026. Primary sources (NCI, FDA) were read in full; review and index sources are marked. Where sources disagree — the membrane-entry question, side-effect mechanisms, reaction percentages — this page carries the disagreement instead of picking a winner.

NCI PDQ — Chronic Myeloid Leukemia Treatment (Health Professional). Ph chromosome in >95% of patients, t(9;22), phases by blast %, incidence and median age. cancer.gov/…/CML/HealthProfessional/Page4 [verified live]
FDA — Gleevec (imatinib mesylate) Prescribing Information, revised July 2026. Dose, bioavailability, protein binding, half-life, metabolism, elimination, mechanism (§12.1), warnings and frequent reactions. accessdata.fda.gov/…/021588s067lbl.pdf [verified live]
Jayavel et al. — "Current and future of targeted therapies against BCR::ABL kinases" (2025). Inactive-conformation binding, downstream pathways, mutations, asciminib's myristoyl-pocket mechanism. pmc.ncbi.nlm.nih.gov/articles/PMC13313521 [verified live]
Elmore — "Apoptosis: A Review of Programmed Cell Death." Shrinkage, pyknosis, ~180–200 bp DNA laddering, blebbing, apoptotic bodies, phagocytosis. pmc.ncbi.nlm.nih.gov/articles/PMC2117903
Thomas et al. — "Active transport of imatinib into and out of cells," Blood 2004 (hOCT1 influx / P-glycoprotein efflux). pubmed.ncbi.nlm.nih.gov/15315971
Imatinib uptake not mediated by OCT1/2/3 (2019) — passive-diffusion model. iris.unil.ch/entities/publication/1c6eb57d…
Gerber — "Targeted therapies" (imatinib side-effect mechanisms: c-KIT and myelosuppression; PDGFR and muscle pain), American Family Physician 2008. aafp.org/afp/2008/0201/p294
EMA — Herceptin (trastuzumab) Summary of Product Characteristics. HER2 subdomain IV binding, ADCC, HER2-testing requirement. ec.europa.eu/…/anx_130985_en.pdf
JCI — "Targeting mutations in cancer." Osimertinib: covalent Cys797 binding, exon 19 deletion / L858R / T790M selectivity. jci.org/articles/view/154943
Haematologica (2026) — review of T315I-era CML therapy: ponatinib and asciminib activity and status. haematologica.org/article/view/14277/80570
FDA — Asciminib accelerated approval for newly diagnosed CML, 29 Oct 2024. fda.gov/…/asciminib-newly-diagnosed…
FDA — Sprycel (dasatinib) Prescribing Information, revised September 2026 (via DailyMed). Indications, dose, mechanism (§12.1 — including the modelling caveat on binding multiple conformations), pharmacokinetics (§12.3), DASISION results (§14.1), side-effect rates. fda.report/DailyMed/4764f37b… [verified live]
Dasatinib for the treatment of chronic myeloid leukemia — patient selection, structure and mechanism; 325× potency vs imatinib in vitro. Dove Medical Press (Drug Design, Development and Therapy). DovePress.com/…dasatinib-for-the-treatment-of-chronic-myeloid-leukemia…
Giannoudis et al. — effective dasatinib uptake in CML cells without hOCT1, Blood 2008 (passive, transporter-independent entry); transporter review, Frontiers in Pharmacology 2021. pmc.ncbi.nlm.nih.gov/articles/PMC2569180
ELN 2025 — recommended TKIs by BCR::ABL1 mutation (dasatinib active vs Y253H, E255K/V, F359V/C/I; not vs T315I, F317L/V/I/C, V299L), via the CML Advocates Network slide set. cmladvocates.net/…New-appoaches-to-overcome-TKI-resistance.pdf
Dasatinib-induced pulmonary hypertension and pleural effusion — case series & literature review, 2025 (PAH ~0.45%; SRC/PDGFRβ mechanism unproven). pmc.ncbi.nlm.nih.gov/articles/PMC12271141

Cell sizes and appearances (myeloblast ~15 µm; segmented neutrophil 10–12 µm; red cell 7–8 µm; capillaries 5–10 µm) follow standard haematology smear-teaching references; imatinib C₂₉H₃₁N₇O, 493.6 Da, per supplier chemistry data; dasatinib C₂₂H₂₆ClN₇O₂S, 488.01 Da, per the FDA Sprycel label §11 and Tocris. The ~1 nm molecular size is an estimate from molecular weight, flagged as such wherever it appears.