Why Do Some Blood Cancers Become Resistant To Treatment?

Author: Aarya Vibhandik

1. Some Cancer Cells Are Resistant From the Beginning

Some blood cancers contain a small group of cells that are already resistant to treatment before therapy begins. Cancer cells within the same tumor can have different genetic and molecular characteristics. This means that while treatment may destroy most of the cancer cells, some resistant cells can survive. After the sensitive cells are removed, the resistant cells can multiply and become more common. Eventually, these cells may cause the cancer to return. This is one reason why a cancer can initially respond well to treatment but later relapse.

2. Cancer Cells Can Change During Treatment

Cancer cells can also develop new changes while a patient is receiving treatment. These changes may allow the cells to survive drugs that previously worked against them. For example, a mutation can change the shape of a protein that a targeted drug is designed to attack. Research on blood cancers has found a mutation called BTK A428D that can make some cancer cells resistant to both BTK inhibitors and newer BTK degraders. This mutation changes the structure of the BTK protein, making it difficult for these drugs to attach to their target. This shows how cancer can evolve in response to treatment.

3. Cancer Cells Can Find Other Ways to Survive

Cancer cells can sometimes avoid treatment by using alternative pathways to keep growing. A drug may block one pathway that cancer cells depend on, but the cells can activate another pathway that sends similar survival signals. Cancer cells can also increase proteins called ABC transporters, which can pump certain drugs out of the cell. When less of the drug remains inside the cancer cell, the treatment may become less effective. These changes can allow cancer cells to continue growing even while the patient is receiving treatment. Researchers are studying combinations of drugs that can block several survival pathways at the same time.

4. The Cancer Environment Can Help Resistant Cells

Cancer cells are affected by the environment around them, which includes immune cells and other types of cells. This environment can sometimes help cancer cells survive treatment. This is especially important with immunotherapy, which works by helping the immune system attack cancer cells. Certain cells in the tumor environment can interfere with immune cells and prevent them from effectively attacking the cancer. Researchers have found that myeloid cells, for example, can weaken T cells and contribute to resistance to some immunotherapies. Understanding the tumor environment may help scientists develop treatments that prevent cancer cells from using their surroundings to survive.