Verywell / Michela Buttignol
Causes of Cancer Drug Resistance
There are two main types of drug resistance.
Intrinsic drug resistance is already present before the treatment starts.
Extrinsic resistance develops in response to the treatment.
Verywell / Michela Buttignol
There are many ways that anticancer drugs work.
This binding causes a cascade of reactions inside the cell that results in the cell dying.
There are many ways that the cells can change these proteins.
The following are ways are the different mechanisms through which cancer develops either intrinsic or extrinsic drug resistance.
Ways that cancer cells develop intrinsic drug resistance include:
Existing Cellular Differences
Cancer cells arent all the same.
Even within one tumor, there can be multiple cancer cell strains with different molecular and genetic characteristics.
Some of these cancer cells may havemutations(changes in their genes) that give them drug resistance.
These cells continue to grow and spread.
Tumor Microenvironment
The conditions in the area around the tumor (its microenvironment) may change during treatment.
For example, certain types of cells can protect the tumor against attacks by the immune system.
Changes that recruit more of these cells to the tumor may include resistance to treatments.
Cancer stem cells have unique properties that give them a special edge against drugs like chemotherapies.
Extrinsic drug resistance can develop at any time.
A tumor may even develop multiple lines of resistance.
Many drugs work by causing damage that leads the cells to kill themselves.
If the pathways that cause this cell death are turned off, the cells can’t kill themselves.
Some drugs need to be modified within the cell to be activated and have their anticancer effects.
Without this metabolism by the cell, the drugs are ineffective.
If the binding isn’t as strong, the drug will be less effective.
The cells may stop expressing the target molecule altogether.
For example,estrogen or progesterone receptors in breast cancersare the target ofhormone therapies.
By enhancing their DNA repair mechanisms, the cancer cells may make these drugs less effective.
These kinds of gene expression changes can also be performed by unique RNA-based structures in the cell called microRNA.
These changes can ramp up or down the number of proteins being created from any given gene.
Changing the Drug Shuttles
Sometimes, changes in cancer cells can reduce the concentrations of drugs inside cells.
MDR1 can stop drugs from entering cells and eject drugs from cells.
Many other approaches to drug resistance are still being tested in cells, animals, or clinical trials.
Using drugs that work in different ways can also help reduce side effects and improve treatment responsiveness.
Researchers are working on other ways to get around drug resistance.
Some tumors may be protected against the immune system by cells like the myeloid cells, which inactivateT cells.
T cells are a pop in of white blood cell that can kill or organize attacks against cancer cells.
This idea is still being investigated in cells.
If tumor growth restarts, your doctor will likely change your treatment approach.
Cancers become resistant to chemotherapy in two major ways.
They either have preexisting resistance to a bang out of drug or they can develop resistance through mutations.
Frequently Asked Questions
Yes, drug resistance is one of the biggest problems in cancer care today.
There are many ways that cancers develop drug resistance.
Cancers that become resistant to a given drug are usually still sensitive to other drugs with different pathways.
Giving multiple drugs in combination can help overcome the resistance that may develop.
Cancer Quest.Cancer drug resistance.
National Cancer Institute.Why do cancer treatments stop working?
2020;12(4).
