Antineoplastic resistance

Definition

Antineoplastic resistance is the resistance of neoplastic (cancerous) cells, or the ability of cancer cells to survive and grow despite anti-cancer therapies.

Other names

The term antineoplastic resistance is often used interchangeably with chemotherapy resistance

Multiple drug resistance

In some cases, cancers can evolve resistance to multiple drugs, called multiple drug resistance.

cancer treatments may stop working due to antineoplastic drug resistance.

Challenging problem

Antineoplastic drug resistance is one of the most challenging problems facing cancer researchers and patients today.

how does it work?

When cancer cells resist the effects of drugs used for treatment, they can grow and reform tumors, a process known as recurrence or relapse.

How fast does it happen?

• Sometimes resistance develops quickly, within a matter of weeks of starting treatment.
• In other cases, it develops months, or even years, later.

Causes

• Resistance can occur when cancer cells—even a small group of cells within a tumor—contain molecular changes that make them insensitive to a particular drug before treatment even begins.
• Because cancer cells within the same tumor often have a variety of molecular changes, this so-called intrinsic resistance is common.
• In other cases of resistance, cancer cells may adapt to the drug while it is being administered, acquiring molecular changes that allow them to escape its effects.
• Molecular alterations that contribute to intrinsic or acquired treatment resistance include mutation of the drug's molecular target, changes in the way the drug interacts with the tumor, broad cellular changes, and changes in the tumor microenvironment, among others.
• To complicate matters, many of these factors can be at play simultaneously in a single tumor.

How to overcome it?

The following are some of the strategies used to fight the antineoplastic resistance.

Combining Cancer Drugs

• Researchers believe one possible way to overcome or delay the development of resistance is to treat patients with combinations of different drugs.
• One combination treatment approach is to "co-administer drugs that work by different molecular mechanisms," Bissan Al-Lazikani, Ph.D., of Cancer Research UK and her colleagues wrote in Nature Biotechnology, "thereby increasing tumor cell killing while reducing the likelihood of drug resistance and minimizing overlapping toxicity."
• Another approach is to treat patients with drugs that block the particular mechanism of resistance their tumors have developed, and then treat them again with the drug to which they grew resistant. The idea is that this combination approach may "re-sensitize" the patients to the original treatment.

Developing Cancer Drugs inside Cells

• One way cancer cells resist treatment is by expelling cancer drugs.
• For example, healthy cells have proteins known as transporters that pump out toxic agents. One such group of proteins, called the ATP-binding cassette (ABC) transporters, expels some chemotherapy drugs, including doxorubicin, and some targeted therapies, like imatinib (Gleevec®).

Using Reversible Modifications

• In addition to arising through genetic alterations, drug resistance can also emerge as a result of alterations in cancer cells' epigenetic codes—molecular modifications that, without altering the DNA code, turn genes on or off.
• A major difference between epigenetics and genetics is that the epigenetic code is reversible and can shift over time.
• One type of epigenetic alteration, called DNA methylation, occurs when enzymes attach chemical tags named methyl groups to DNA.
• Another type, termed histone modification, occurs when enzymes attach chemical tags to histones, proteins that are involved in "packaging" DNA into compact structures.
• Both DNA methylation and histone modifications can turn nearby genes on or off.

Altering the Tumor Microenvironment=

• Immunotherapies—therapies that help the immune system to fight cancer—have generated robust and durable responses in patients with various types of cancer. But, like other therapies, immunotherapies don't work some patients and for others, they stop working after initially working.

Antineoplastic resistance Resources
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