Resistance Bypass Engine

Evidence-first oncology resistance analysis

5 DATA SOURCES AVAILABLE

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Acquired resistance / evidence review

Examine resistance.
Review the evidence.

Enter a treatment and a resistance-related gene change. The report checks the gene names, maps related proteins, and shows the supporting records and missing evidence.

Start an analysis Browse resistance scenarios

05 biological databases 02 resistance patterns 01 reproducible report ID

How the report is built

01 Check the genesOfficial gene and protein records HGNC · UniProt

02 Map related proteinsKnown protein interactions STRING

03 Review the evidenceDisease, drug, and study records Clinical data

sequence / acquired resistanceEGFR → MET

Evidence-based starting points

Begin with a documented resistance pattern.

19reviewed examples across 11 cancer types. Start with a known resistance pattern, then examine the current database records.

FEATURED / NSCLC

EGFR inhibition → MET amplification

Review reported MET-associated alternative signaling after progression on osimertinib.

Open live analysis →

Evidence review / new analysis

Build a resistance evidence report.

Describe the treated target and the change observed after therapy. The report connects gene records, protein interactions, drug activity, and clinical sources without turning a research score into a treatment recommendation.

Method / limits

What the analysis can—and cannot—show.

The tool distinguishes a biological link from evidence that a treatment works. It can organize findings for expert review, but it cannot determine patient suitability, dose, expected response, or treatment benefit.

Check namesMatch common gene names, such as HER2, to their official HGNC, UniProt, Ensembl, and ChEMBL records.

Map interactionsBuild a protein-interaction map from live databases and state when a source is unavailable.

Assess supportShow what supports the result, what conflicts with it, and which drug-activity data are missing.

Data sources / report details

Five biological databases are checked.

Each report shows which databases responded, when they were checked, what evidence they returned, and a non-identifying ID for repeating the same request.

HGNC + UniProtOfficial gene names and reviewed human protein records.

STRING-DBReported physical interactions between proteins.

Open Targets + ChEMBLDrug, disease, clinical-development, and laboratory activity records.

How to read the report

Research priorityOrders results for expert review. It is not measured drug synergy or a treatment recommendation.

Network influenceDescribes where a protein sits in the interaction map. Drugs aimed at the same protein can therefore receive the same value.

Supporting evidenceShows whether the result has relevant disease, drug-activity, and drug-pair records. Missing evidence remains visible.

Clinical resistance scenariosBrowse 19 reviewed examples across 11 cancer types. Open library

Reported resistance patterns

Choose a documented resistance example from 11 cancer types. Each example fills in the gene change, prior treatment, and cancer type before opening the live analysis.

Find a resistance pattern 19 reviewed scenarios · 11 cancer types

Showing 19 reviewed scenarios

No scenario matches those filters. Try a gene, mutation, drug, or cancer type.

EGFR + MET Amplification MET amplification after treatment · check sample and assay

Chr 7p11.2 (EGFR) ➔ Chr 7q31.2 (MET)

Proposed mechanism: MET amplification may support signaling through ERBB3 and PI3K despite EGFR inhibition with osimertinib.

EGFR + C797S Secondary Mutation Drug-binding change · confirm the reported variant

Chr 7p11.2 (Exon 20 C797S)

Proposed mechanism: EGFR C797S changes the drug-binding site and can reduce covalent binding of osimertinib.

ALK + MET signaling Alternative receptor signaling · check prior ALK therapy

Chr 2p23.2 (ALK) ➔ Chr 7q31.2 (MET)

Proposed mechanism: MET activation may provide an alternative signaling route during alectinib treatment in ALK-positive NSCLC.

ROS1 + G2032R Solvent-front mutation · inspect TKI history

Chr 6q22.1 (ROS1 G2032R)

Mechanism: A solvent-front substitution can impair binding of earlier ROS1 inhibitors. Drug sensitivity remains inhibitor-specific and must be checked against the current clinical record.

Primary translational evidence ↗

HER2 + MET Amplification Possible MET-associated resistance · confirm HER2 and MET status

Chr 17q12 (ERBB2) ➔ Chr 7q31.2 (MET)

Proposed mechanism: Increased MET signaling may provide an alternative pathway during trastuzumab treatment.

ESR1 + CDK4/6 signaling After endocrine therapy · specify prior treatment

Chr 6q25.1 (ESR1) ➔ Chr 12q14.1 (CDK4)

Proposed mechanism: Ligand-independent ESR1 variants and Cyclin D1/CDK4 activity may support growth after aromatase-inhibitor treatment.

ESR1 + Y537S Ligand-independent activation · variant-specific

Chr 6q25.1 (ESR1 Y537S)

Mechanism: Y537S stabilizes an active estrogen-receptor conformation and is associated with acquired endocrine resistance; it does not establish sensitivity to a particular subsequent regimen.

Primary structural evidence ↗

KRAS G12C + EGFR signaling Return of EGFR signaling · check prior KRAS therapy

Chr 12p12.1 (KRAS) ➔ Chr 7p11.2 (EGFR)

Proposed mechanism: EGFR activity can restore MAPK signaling during KRAS G12C inhibition, providing a reason to study both targets together.

BRAF V600E + EGFR signaling Approved only in specified clinical settings

Chr 7q34 (BRAF) ➔ Chr 7p11.2 (EGFR)

Proposed mechanism: EGFR activity can restore MAPK signaling during BRAF inhibition. Encorafenib plus cetuximab is FDA-authorized in specified BRAF V600E metastatic colorectal cancer settings.

BRAF V600 + MAP2K1/MEK1 MAPK reactivation • confirm acquired alteration

Chr 7q34 (BRAF) ➔ Chr 15q22.31 (MAP2K1)

Mechanism: MAPK reactivation is a documented resistance biology; dabrafenib plus trametinib is authorized only for specified BRAF V600 melanoma, NSCLC, thyroid, and other labeled indications—not as a universal resistance rescue.

BCR–ABL1 + T315I Drug-binding change · specify previous TKIs

Chr 9q34.12 (ABL1 T315I Gatekeeper)

Mechanism: Threonine-to-isoleucine substitution alters the kinase binding site; ponatinib or asciminib are approved options in specified CML/Ph+ ALL settings, while combination use requires its own evidence.

AR + PI3K signaling Confirm PTEN/PI3K test result and prior therapy

Chr Xq12 (AR) ➔ Chr 3q26.32 (PIK3CA)

Proposed mechanism: Androgen-receptor and PI3K–AKT signaling can regulate one another in metastatic castration-resistant prostate cancer.

PIK3CA + KRAS signaling RAS/MAPK co-alteration • confirm tumor subtype

Chr 3q26.32 (PIK3CA) ➔ Chr 12p12.1 (KRAS)

Proposed mechanism: RAS–MAPK activation may maintain signaling during selective PI3Kα inhibition.

PARP inhibition + BRCA2 reversion HR restoration · confirm paired sequencing

Chr 13q13.1 (BRCA2 reversion)

Mechanism: A secondary reversion can restore BRCA2 open-reading-frame function and homologous recombination, providing a documented route to PARP-inhibitor resistance.

Primary mechanistic evidence ↗

EGFRvIII + MET Amplification Confirm EGFR and MET results in the relevant sample

Chr 7p11.2 (EGFRvIII) ➔ Chr 7q31.2 (MET)

Proposed mechanism: Concurrent signaling through EGFRvIII and MET may reduce dependence on EGFR alone in high-grade glioma.

RET fusion + MET signaling Possible MET-associated resistance · confirm progression on RET therapy

Chr 10q11.21 (RET) ➔ Chr 7q31.2 (MET)

Proposed mechanism: MET amplification has been reported after treatment with the selective RET inhibitor selpercatinib.

RET + G810 solvent-front mutation On-target binding change · substitution-specific

Chr 10q11.21 (RET G810R/S/C)

Mechanism: G810 solvent-front substitutions can sterically interfere with selective RET-inhibitor binding. The returned report must not be read as evidence for a replacement therapy.

Primary clinical evidence ↗

KIT + V654A Secondary ATP-pocket mutation · exon-specific

Chr 4q12 (KIT V654A)

Mechanism: The secondary KIT V654A substitution alters the ATP-binding pocket and is associated with acquired imatinib resistance in GIST.

Primary model evidence ↗

FGFR2 + V565F Gatekeeper mutation · polyclonal resistance possible

Chr 10q26.13 (FGFR2 V565F)

Mechanism: Secondary FGFR2 kinase-domain mutations, including V565 gatekeeper substitutions, are documented after FGFR-inhibitor therapy in FGFR2-altered cholangiocarcinoma.

Primary resistance landscape ↗

01 / Define the caseTreatment and resistance details

Primary target gene

Targeted therapy

Resistance-associated gene

Describe the observed changes optional but useful

Initial gene change (optional)

Resistance-related change (optional)

Type of gene change (optional)

When resistance was identified (optional)

Cancer type

Use this report to organize research evidence. It does not determine treatment suitability or predict response.

02 / Evidence reportProtein interactions and research priorities

Case preview

The report will follow this treatment-to-resistance relationship.

Ready to analyze

TARGETEGFRtreated protein

targeted by

Osimertinib

resistance observed

CHANGEMETNSCLC context

01Confirm the recordsMatch gene and protein names to reviewed database entries.HGNC · UNIPROT

02Retrieve interactionsBuild a connected map from reported protein interactions.STRING

03Review the supportSeparate network findings from drug and clinical evidence.OPEN TARGETS · CHEMBL

01 / CHECKOfficial gene recordsMatch common gene names to HGNC, UniProt, Ensembl, and ChEMBL records.

02 / MAPProtein interactionsRetrieve reported protein interactions and relevant drug and disease records.

03 / REVIEWStrength of evidenceKeep the research score separate from clinical evidence and clearly show missing data.

How the analysis works

Run an analysis to view reported protein interactions, evidence records, and any linked experimental protein structure.

Primary Target: - Resistance Marker: - Source timing: —

01 · Gene records confirmed 02 · Interactions retrieved 03 · Evidence reviewed 04 · Research priorities calculated

Resistance Type

Network Nodes

0.000

Network Distance

Reported protein interaction network

Primary Target Resistance Marker Additional Drug Target Intermediate Protein

⌬ Experimental protein structure

Inspect an experimental structure linked to the selected protein. If none is available, the report states this clearly.

Select a node

Run an analysis to check for a linked experimental structure.

Structure record

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PDB —

This panel shows whether a reviewed PDB record is linked to the selected protein.