Why Cancer Medicines Stop Working

Cancer is a very serious disease. Doctors give patients medicine to fight cancer. But sometimes the medicine stops working. The cancer cells learn to hide from the medicine. This article explains why this happens.

How Do Cells Work?

Every cell in your body has instructions. These instructions are called DNA. DNA tells the cell what to do. DNA tells the cell: “Grow now” or “Stop growing” or “Die now.”

Cancer cells have bad instructions. Their DNA is broken. The cancer cells do not listen to the stop signal. They just keep growing and growing.

But there is more. Cancer cells also have a control system. This control system is like an on/off switch for genes. It can turn genes ON or turn genes OFF. The cancer cells use this control system to hide from medicine.

The Control System: Like a Light Switch

Imagine DNA is a book. In a normal cell, the book is open. You can read the instructions. But in a cancer cell, the book is closed with a lock. You cannot read the instructions.

The cancer cell puts locks on important genes. These locks are called “marks.” The marks hide the genes. The genes cannot work. This is how cancer cells hide from medicine.

For example:

• A cancer cell puts a lock on the “stop growing” gene
• The cell cannot read this gene
• So the cell does not stop growing
• The cancer cell grows more and more

How Medicine Fights Cancer

Doctors have different medicines for cancer:

Chemotherapy: This medicine kills all cells that grow fast. Cancer cells grow very fast, so chemotherapy kills many cancer cells. But it also kills some good cells.

Targeted Medicine: This medicine targets one specific protein in the cancer cell. For example, if a cancer cell has too much of a protein called “HER2,” the medicine will attack only this protein.

Immune Medicine: This medicine helps your immune system see the cancer cells. Your immune system is like soldiers in your body. Normally, the cancer cells hide from these soldiers. The immune medicine helps the soldiers find and kill the cancer cells.

The Big Problem: The Medicine Stops Working

A patient takes medicine for cancer. In the first month, the medicine works very well. The cancer gets smaller. But after three or four months, something bad happens.

The cancer cells learn a trick. They find a way to escape the medicine. Now the medicine does not work anymore. The cancer starts to grow again.

Why does this happen?

• The cancer cells pump the medicine out of the cell
• The cancer cells change the protein that the medicine targets
• The cancer cells use the control marks to hide from the medicine
• The cancer cells make new changes to survive without the targeted protein

New Medicines That Target the Control System

Scientists have a new idea. Instead of killing the cancer cells directly, they can remove the locks on the genes. If you remove the locks, the hidden genes can work again. And some of these genes tell the cancer cell to die.

HDAC Inhibitors – The Key to Open the Locks

HDAC is the name of the lock on the genes. HDAC inhibitors are like keys. They open the locks.

When the locks open:

• Hidden genes can work again
• The “die” genes turn on
• The cancer cells start to die
• The immune system can see the cancer cells better

Doctors use HDAC inhibitors for blood cancers. This medicine works slowly, but it works well for patients who have already used other medicines.

BET Inhibitors – Breaking the Communication

BET is a protein that helps cancer cells talk to each other. BET inhibitors stop this communication.

Without communication:

• Cancer cells cannot get the signals to grow
• Cancer cells stop growing
• Cancer cells start to die

BET inhibitors work very well for some blood cancers, especially cancers with too much MYC protein.

DNA Methylation Medicines – Removing the Other Locks

DNA methylation is another type of lock on genes. It is different from HDAC locks. DNA methylation medicines remove these other locks.

When you remove DNA methylation locks:

• The immune system can see the cancer cells
• The “die” genes turn on
• The cancer cells look “foreign” to the body
• The immune system attacks and kills the cancer cells

Two Medicines Are Better Than One

One new idea is to use two medicines together. If cancer cells can escape one medicine, they may not be able to escape two medicines at the same time.

Example 1: HDAC inhibitor + Immune medicine

• HDAC inhibitor opens the locks on genes
• Immune medicine helps your immune system attack
• Together they are much stronger

Example 2: DNA methylation medicine + Immune medicine

• DNA methylation medicine opens locked genes
• Immune medicine attacks the exposed cancer cells
• Together they work very well

How to Know Which Patient Will Get Better

Not all patients get better with the same medicine. Some patients improve a lot. Some patients improve a little. Some patients do not improve.

Doctors need to know which patients will benefit. Scientists are looking for “signs” in the cancer cells. These signs tell the doctor: “This medicine will work for this patient.”

These signs are:

• Special marks on the DNA
• Which genes are open and which are closed
• Pieces of cancer DNA in the blood
• Testing if the medicine actually works on the patient’s cancer in the lab

Blood Tests: A Simple Way to Watch the Cancer

When cancer cells die, they release DNA into the blood. Scientists can now find this DNA in a simple blood test.

This blood test is useful because:

• It is easy – just a normal blood test
• Doctors can do it many times
• It shows if the treatment is working
• It can find very small amounts of cancer
• It can find new changes in the cancer

In the future, all cancer patients will probably have blood tests every month. If the cancer is changing and developing new escape tricks, the doctor can change the medicine.

The Future: Each Patient Gets the Right Medicine

Today, all cancer patients with the same type of cancer get the same medicine. But in the future, each patient will get a different medicine. The medicine will be perfect for that patient’s specific cancer.

The steps will be:

• Step 1: Take cancer cells from the patient
• Step 2: Test the cancer cells in the lab
• Step 3: Choose the best medicine for this patient’s cancer
• Step 4: Give the medicine and do blood tests to watch
• Step 5: If the cancer is changing, change the medicine early

What Doctors Need to Know Now

• Cancer cells hide from medicine by using control marks on DNA
• New medicines can remove these locks and make cancer cells die
• Using two medicines together is stronger than one medicine
• Blood tests can now watch cancer and find changes early
• In the future, each patient will get the medicine that works for their cancer

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Cancer treatment is changing. We now understand why cancer medicines stop working. This helps us make better medicines. In the future, we can help more patients live longer and healthier lives.