Small-molecule kinase inhibitors
Pills that block the specific enzyme a cancer relies on. Imatinib in 2001 proved a cancer could be switched off by design.
Over 80 approved kinase inhibitors: EGFR (osimertinib), ALK (lorlatinib), BRAF/MEK, KRAS G12C, RET, NTRK, MET, FGFR, BTK, JAK, CDK4/6, PI3K/AKT, VEGFR, FLT3, KIT. Resistance through gatekeeper mutations, bypass pathways, and lineage change drives successive generations. Allosteric, covalent, and macrocyclic designs extend the reach.
How it works
ATP-competitive or allosteric binding to the kinase domain blocks phosphotransfer.
- Oral, outpatient
- Dramatic responses in oncogene-addicted cancers
- Near-universal resistance in metastatic disease
- Off-target toxicities
Acalabrutinib is a cleaner BTK blocker with fewer heart and bleeding problems than ibrutinib. In February 2026 it became half of the first all-oral, fixed-duration CLL regimen.
Afatinib (Gilotrif) is an irreversible EGFR pill for lung cancer, notable for activity against uncommon EGFR mutations (G719X, L861Q, S768I).
Alectinib is a well-tolerated ALK pill, standard first line for years and, since 2024, the first targeted therapy given after surgery for ALK-positive lung cancer.
Alpelisib was the first PI3K drug for PIK3CA-mutant breast cancer (2019). It is effective, but high blood sugar and rash limited its use, and newer drugs are displacing it.
Asciminib is a BCR::ABL1 blocker that binds a different pocket from every other TKI, approved for all newly diagnosed chronic myeloid leukaemia in 2024 and now being tested in Ph-positive ALL.
Avapritinib is the first drug for GIST driven by the PDGFRA D842V mutation, which resists every other kinase inhibitor; it is also approved for systemic mastocytosis.
Avutometinib plus defactinib is the first treatment approved specifically for low-grade serous ovarian cancer, a slow-growing type driven by the RAS pathway.
Axitinib is a selective VEGF-receptor pill, now given mainly with pembrolizumab or avelumab as first-line kidney cancer treatment.
Belumosudil is a pill for chronic graft-versus-host disease, the long-term immune complication of donor stem-cell transplants used to cure blood cancers.
Belzutifan is the first HIF-2α inhibitor, born from Nobel-winning biology, and is now approved after kidney cancer surgery with pembrolizumab.
Binimetinib is the MEK inhibitor partnered with encorafenib; blocking the next step in the same relay stops the tumour rerouting around the BRAF block.
Bortezomib was the first proteasome inhibitor: it jams the cell's protein-recycling machine, which antibody-factory plasma cells cannot tolerate.
Bosutinib is a CML pill with less cardiovascular and pleural toxicity than its rivals; its main side effect is diarrhoea.
Brigatinib is an ALK pill with strong brain activity, approved first after crizotinib and then first line after beating it in ALTA-1L.
A pill that blocks both blood-vessel growth and the MET escape pathway, used in kidney, liver, thyroid and, since 2025, neuroendocrine cancers.
Capivasertib (Truqap) is the first AKT inhibitor, for breast cancer with PI3K-pathway mutations and, since 2026, for prostate cancer with PTEN loss.
Capmatinib and tepotinib are two pills for the roughly 3% of lung cancers with a MET exon 14 skipping mutation.
Ceritinib is a second-generation ALK pill for lung cancer, effective after crizotinib but with gastrointestinal toxicity that limited uptake.
Cobimetinib is the MEK partner for vemurafenib, and the first drug approved for histiocytic neoplasms.
Copanlisib is an intravenous PI3K inhibitor for relapsed follicular lymphoma, approved in 2017 and withdrawn in 2023 when its confirmatory trial failed.
Crizotinib was the first ALK inhibitor, approved four years after ALK fusions were found in lung cancer; it was also the first drug for ROS1 lung cancer and for ALK-positive lymphoma and inflammatory myofibroblastic tumour in children.
Dabrafenib plus trametinib is the BRAF-plus-MEK pill combination, approved for BRAF V600E lung cancer and, since 2022, for any solid tumour with that mutation.
A second-generation EGFR pill that beat gefitinib on survival in EGFR-mutant lung cancer but was quickly overshadowed by osimertinib.
Dasatinib is a second-generation BCR::ABL1 pill that, combined with the immunotherapy blinatumomab, can put Ph-positive ALL into deep remission with no chemotherapy at all.
A dual PI3K inhibitor for relapsed CLL whose survival data raised FDA concern; use is now limited to late lines.
Encorafenib is a BRAF inhibitor that, with cetuximab and chemotherapy, became first-line standard for BRAF-mutant colorectal cancer in 2026.
A Chinese-developed ALK pill approved in the US in December 2024 for first-line ALK-positive lung cancer.
Entrectinib (Rozlytrek) is a pill for NTRK-fusion cancers and ROS1 lung cancer that reaches brain metastases.
The first targeted pill for bladder cancer, for the roughly 20% of tumours with FGFR3 alterations, used after immunotherapy.
Erlotinib was one of the first EGFR pills for lung cancer; it was approved before anyone knew EGFR mutations predicted who would respond, then redefined by them.
An mTOR-blocking pill that doubled progression-free time with exemestane in 2012 and is now paired with the oral SERD giredestrant.
A second JAK inhibitor for myelofibrosis that works after ruxolitinib fails; it carries a boxed warning for a rare brain toxicity (Wernicke encephalopathy) so thiamine is checked.
A Chinese-discovered pill that blocks the blood-vessel receptors, approved in 2023 for bowel cancer after all standard treatments.
Futibatinib is a covalent FGFR inhibitor for FGFR2-fusion bile duct cancer, with the highest response rate of the first-generation drugs.
An intravenous drug that blocks the whole PI3K/mTOR pathway, approved in July 2026 for hormone-positive breast cancer.
The lung-cancer pill whose dramatic responses in a few patients led to the discovery of EGFR mutations in 2004.
A single pill that beats salvage chemotherapy for relapsed FLT3-mutated AML, and the backbone of the triplets now being tested in frontline disease.
Glasdegib is a hedgehog-pathway pill that, with low-dose chemotherapy, extends survival in older AML patients who cannot have intensive treatment; it has largely been displaced by venetoclax combinations.
The pill that ended chemotherapy for most CLL. It blocks the survival signal B cells depend on, and it was the first drug to beat chemoimmunotherapy in nearly every CLL setting.
Idelalisib was the first PI3K inhibitor for blood cancers; it is effective in CLL with rituximab but so toxic (colitis, hepatitis, pneumonitis, infections) that the class has largely been abandoned.
The drug that started the targeted therapy era in 2001, turning chronic myeloid leukaemia into a manageable condition with near-normal life expectancy.
Inavolisib is a PI3K drug that also destroys the mutant protein, approved in 2024 with palbociclib and fulvestrant for PIK3CA-mutant breast cancer.
Ivosidenib is a pill that blocks the mutant IDH1 enzyme, approved in bile duct cancer and in leukaemia.
Ixazomib (Ninlaro) is the first oral proteasome inhibitor for multiple myeloma, enabling an all-oral triplet with lenalidomide and dexamethasone.
Lapatinib was the first HER2-blocking pill (2007) and is now mostly a comparator arm and a late-line option, displaced by tucatinib and ADCs.
The first drug approved for a gene fusion regardless of where the cancer started; it works in about 75% of NTRK-fusion cancers, from infant fibrosarcoma to salivary and thyroid cancers.
A third-generation EGFR pill used together with amivantamab as the first regimen to beat osimertinib in EGFR-mutant lung cancer.
An oral anti-angiogenic pill that matched sorafenib in liver cancer with higher response rates, and partners with pembrolizumab in kidney and endometrial cancer.
An ALK inhibitor with the longest disease control ever recorded for a targeted lung cancer pill: 60% progression-free at five years.
The first drug to improve survival in FLT3-mutated AML, added to standard chemotherapy: median survival went from about two years to more than six.
Mobocertinib was the first oral drug for EGFR exon 20 insertion lung cancer, approved in 2021 and withdrawn in 2023-24 after its confirmatory trial failed.
Momelotinib is the JAK inhibitor designed for anaemic myelofibrosis patients: it can improve haemoglobin while shrinking the spleen.
A fourth-generation ALK pill that works after lorlatinib and avoids the TRK-related brain side effects; under FDA priority review with a decision due 27 November 2026.
Nemtabrutinib is Merck's reversible BTK blocker, active against the C481S escape mutation, being tested against ibrutinib and acalabrutinib in first-line CLL.
A pill taken for a year after trastuzumab to further reduce recurrence in HER2-positive, hormone-positive breast cancer, limited by severe diarrhoea.
Nilotinib is a second-generation CML pill that produces deeper responses faster than imatinib, at the cost of cardiovascular and metabolic side effects.
An anti-angiogenic pill that looked promising in mesothelioma in a small trial but failed in the large one.
Nirogacestat is the first approved medicine for desmoid tumours, locally invasive growths that do not spread but can be crippling; it works by blocking Notch signalling.
Osimertinib (Tagrisso) is the standard pill for EGFR-mutant lung cancer, now also given after surgery and with chemotherapy or after chemoradiation.
The JAK inhibitor for myelofibrosis patients whose platelet counts are too low for ruxolitinib.
Pazopanib is the only multi-kinase inhibitor approved for soft-tissue sarcoma (excluding fat-derived tumours), used after chemotherapy fails.
Pemigatinib was the first targeted therapy for bile duct cancer, for tumours with an FGFR2 gene fusion.
Pexidartinib is the first drug for tenosynovial giant cell tumour, a benign but destructive joint tumour; it is effective but has liver toxicity that requires a restricted programme.
A BTK blocker that works after the older ones stop, because it grips a different part of the enzyme. Fully approved for CLL in December 2025.
Ponatinib is the only BCR::ABL1 inhibitor that covers the T315I resistance mutation. In 2024 it became the preferred pill for newly diagnosed Ph-positive ALL.
Pralsetinib is the second selective RET pill for lung cancer, less used than selpercatinib after a change of owner and label.
Pyrotinib is China's HER2 pill, widely used there with capecitabine and as a comparator for the new Chinese HER2 ADCs.
Quizartinib is a more selective FLT3 blocker that, added to chemotherapy, roughly doubled median survival in the highest-risk FLT3 subtype.
A sorafenib successor that became the first second-line drug proven to prolong life in liver cancer (2017).
A ROS1 and NTRK pill that also works after other ROS1 drugs fail, with dizziness as its signature side effect.
A fourth-line GIST drug that locks KIT in an off state regardless of which resistance mutation the tumour has acquired.
Ruxolitinib was the first JAK inhibitor: it shrinks the spleen and relieves symptoms in myelofibrosis and controls blood counts in polycythaemia vera, without eliminating the disease clone.
Selinexor is a first-in-class pill that traps tumour-suppressor proteins inside the nucleus; approved in myeloma, it failed its endometrial cancer test in 2026.
Selpercatinib is a selective RET inhibitor approved for any tumour with a RET fusion, with a further label update in July 2026.
Sevabertinib is an oral HER2 inhibitor for lung cancers with HER2 mutations, approved in November 2025 as an alternative to Enhertu and zongertinib.
Sonidegib (Odomzo) is the second hedgehog inhibitor for locally advanced basal cell carcinoma, similar in effect and side effects to vismodegib.
Sonrotoclax is a more potent, shorter-acting successor to venetoclax. It was approved for mantle cell lymphoma in May 2026 and is in late-stage trials with zanubrutinib for CLL.
The first drug ever to extend life in advanced liver cancer (2007), now mostly a comparator arm that newer combinations are measured against.
Sunitinib is an anti-angiogenic pill approved for pancreatic neuroendocrine tumours, kidney cancer and GIST.
An oral drug for EGFR exon 20 insertion lung cancer that succeeded where mobocertinib failed; approved in China (2023) and the US (2025).
A ROS1 lung-cancer pill approved in 2025 that works in the brain and after crizotinib, with fewer dizziness-type side effects than repotrectinib.
A weekly infusion that was the first drug to extend survival in poor-risk kidney cancer (2007), and in 2024 the first targeted drug to improve outcomes in childhood rhabdomyosarcoma.
A next-generation FGFR inhibitor designed to work after pemigatinib or futibatinib stop working, now in a global phase 3.
Tivozanib is a highly selective VEGF-receptor pill for kidney cancer after two or more prior treatments, notable for its tolerability and for a trial that closed the door on immunotherapy rechallenge.
Tovorafenib is a pill for the most common childhood brain tumour, low-grade glioma driven by BRAF changes, approved in 2024.
A HER2-selective pill that works in the brain, for HER2-positive breast cancer with brain metastases.
A PI3K inhibitor for marginal zone and follicular lymphoma approved in 2021 and withdrawn in 2022 after the UNITY-CLL trial suggested more deaths.
Vandetanib was the first drug approved for medullary thyroid cancer (2011), now largely replaced by RET-selective selpercatinib.
Vemurafenib was the first BRAF inhibitor (2011); it shrank melanomas in weeks and proved that a single mutation could be drugged in a solid tumour.
A pill that removes the survival shield from leukaemia cells, enabling chemotherapy-free, time-limited treatment for CLL.
Vimseltinib is a pill approved in February 2025 for tenosynovial giant cell tumour, a benign but destructive joint tumour, offering an alternative to repeated surgery.
Vismodegib was the first hedgehog-pathway drug, for basal cell carcinomas too advanced for surgery; it shrinks most tumours but muscle cramps, taste loss and hair loss make long-term use hard.
Zanubrutinib is the only BTK blocker to beat ibrutinib on both efficacy and safety in a head-to-head trial. It is now the most prescribed BTK inhibitor in CLL.
A ROS1 inhibitor approved in July 2026 that works after other ROS1 drugs fail and avoids their brain side effects.
Zongertinib was the first oral HER2 inhibitor for lung cancer with HER2 mutations, approved in 2025 and moved to first line in 2026.
Patients with newly diagnosed metastatic colorectal cancer whose tumour carries a BRAF V600E mutation, which is about 8-12% of cases, should now be offered encorafenib and cetuximab together with FOLFOX from the start rather than after chemotherapy fails; median survival has roughly doubled to about two and a half years. BRAF testing at diagnosis is therefore essential, alongside RAS and mismatch repair testing. The regimen is more toxic than chemotherapy alone.
Patients newly diagnosed with EGFR-mutated advanced lung cancer now have a first-line option that improves survival over osimertinib, particularly if they have high-risk features. The trade-off is intravenous (now subcutaneous) infusions and considerably more skin, nail and clotting toxicity, so osimertinib alone remains reasonable for those who prioritise convenience and tolerability. Both this regimen and osimertinib plus chemotherapy (FLAURA2) are approved; there is no direct comparison.
Patients with KRAS G12C lung cancer that has progressed after chemo-immunotherapy can take an oral KRAS inhibitor instead of docetaxel and gain a somewhat longer time to progression with fewer severe side effects, but should understand that most tumours become resistant within a year and that survival is not improved. KRAS G12C testing is worthwhile, but first-generation inhibitors are a step rather than a cure; combinations and next-generation inhibitors are the active research fronts.
Young adults with a grade 2 IDH-mutant glioma who have had surgery can now take a daily tablet that slows or reverses tumour growth and defers radiotherapy and chemotherapy, both of which carry long-term cognitive costs, by years. It confirms that the IDH mutation is a driver that can be targeted, not just a marker. Whether it improves survival or cognition over the long term, and whether it helps in higher-grade or previously treated tumours, is unknown.
Patients with newly diagnosed advanced clear-cell kidney cancer should receive an immunotherapy-based combination; lenvatinib plus pembrolizumab gives the highest response rate and longest PFS of the available options, at the cost of more side effects requiring dose adjustment. Sunitinib alone is no longer an appropriate standard. Choosing among the combinations depends on risk group, symptoms, comorbidity and the value placed on treatment-free survival, which favours nivolumab plus ipilimumab in intermediate and poor risk.
The dose on the label is often not the best dose for patients; it is the highest one that was tolerable for a few weeks. Project Optimus means new cancer drugs should arrive with evidence on dose, and it gives clinicians licence to consider dose reduction for toxicity. For older drugs, the evidence gap persists.
Every resected non-squamous lung cancer should be tested for EGFR mutations, because patients who carry one live longer if they take osimertinib for three years after surgery. The trial does not tell us whether adjuvant chemotherapy can be omitted, nor what happens on relapse after osimertinib, and the three-year duration was chosen empirically.
For ALK-positive advanced lung cancer, lorlatinib as the first drug offers the possibility of many years without progression and strong protection against brain metastases. Alectinib and brigatinib remain alternatives with a gentler side-effect profile; the choice weighs lorlatinib's cognitive, metabolic and weight effects against its unmatched duration of control.
Anyone diagnosed with advanced lung cancer should have EGFR testing before treatment, because osimertinib as the first drug gives the longest disease control, protects the brain, and is well tolerated. Chemotherapy is not the first step for these patients. The remaining questions are whether to intensify upfront (adding chemotherapy or amivantamab) and how to treat resistance when it develops.
The most frequently mutated oncogene in cancer stopped being undruggable, and patients with KRAS G12C lung and bowel cancers now have targeted pills. The approach, exploiting a mutation-created chemical handle and an inactive-state pocket, has become a template for other hard targets.
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