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The genetics of drug resistance: why a medicine stops working

Sometimes a medicine works well at first and then becomes less effective. Often the reason is new genetic changes in the leukaemia cells; this is called drug resistance.

Last updated: ~1 min read
A single yellow-and-white capsule on an open palm
Figure 1.Why a medicine can stop working

01Short answer

The target protein can change so the medicine no longer binds well (for example, kinase domain mutations in BCR::ABL1 in CML). Or the cell learns to survive another way. Sometimes resistant cells are present in small numbers from the start and are selected and multiply during treatment. Testing finds these changes and helps choose the next medicine. Taking the medicine regularly, exactly as prescribed, lowers the risk of resistance.

02Simple explanation

The target changes.

Selection.

Test and choose again.

Regular intake.

03Scientific explanation

NCI: drug resistance is when cancer cells do not respond to a medicine; it can be present from the start or develop during treatment.

NCI: new treatments are tested step by step, from the laboratory to clinical trials; only those proven safe and beneficial become standard care.

04What happens in the body?

Clonal evolution

The disease cells changing over time.

A growing clone
Figure 2.A growing clone — The genetics of drug resistance: why a medicine stops working

Kinase domain mutation

A common cause of resistance to TKIs.

Two keys
Figure 3.Two keys — The genetics of drug resistance: why a medicine stops working

How to read the news

Research news brings hope, but not every advance suits everyone. Look at who it was tested in, at what phase and in how many people.

Talk to your doctor

Show your doctor what you have read; they will explain how it relates to your diagnosis and treatment. Do not change your treatment on your own.

05From research news to a conversation: four steps

Read, check, ask, decide together.

Read — From a trusted source.1ReadFrom a trusted source.
Check — Phase, participants, result.2CheckPhase, participants, result.
Ask — Show your doctor.3AskShow your doctor.
Decide — Together, without rushing.4DecideTogether, without rushing.
SourceA trusted site.
DoctorA personal explanation.
SafetyNot changing treatment yourself.

06Key points at a glance

TopicIn brief
Clonal evolutionThe disease cells changing over time.
Kinase domain mutationA common cause of resistance to TKIs.
How to read the newsResearch news brings hope, but not every advance suits everyone. Look at who it was tested in, at what phase and in how many people.
Talk to your doctorShow your doctor what you have read; they will explain how it relates to your diagnosis and treatment. Do not change your treatment on your own.

07Key terms

Drug resistance
Loss of a medicine's effect.
Clone
A group of cells descended from one cell.
Clinical trial
Testing a new treatment with volunteers.
Evidence
A result confirmed by reliable research.

08Key points

  • Take it.
  • Test.
  • Switch.
  • Check the source.
  • Talk to your doctor.

09Frequently asked questions

Is resistance my fault?

No, it is usually the biology of the disease; but not missing doses matters.

Is there another medicine?

Often yes; your doctor will choose based on testing.

Is this advance right for me?

Only your treating doctor can say, based on your diagnosis, stage and condition.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is resistance my fault?

  2. Is there another medicine?

  3. Is this advance right for me?

My questions

12Sources

  1. National Cancer Institute. NCI Dictionary of Cancer Terms: drug resistance
  2. National Cancer Institute. Chronic Myelogenous Leukemia Treatment (PDQ®) – Patient Version
  3. National Cancer Institute. What Are Clinical Trials?
  4. National Cancer Institute. Phases of Clinical Trials
  5. National Cancer Institute. Using Trusted Resources
  6. National Cancer Institute. NCI Dictionary of Cancer Terms: conditioning regimen
  7. National Cancer Institute. NCI Dictionary of Cancer Terms: bioinformatics
  8. National Cancer Institute. NCI Dictionary of Cancer Terms: microscope
  9. National Cancer Institute. NCI Dictionary of Cancer Terms: eligibility criteria
  10. World Health Organization. International Clinical Trials Registry Platform
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
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