Antineoplastic resistance

Antineoplastic Resistance

Antineoplastic resistance mechanisms

Antineoplastic resistance refers to the ability of cancer cells to withstand the effects of chemotherapy drugs designed to kill or inhibit their growth. This resistance can be intrinsic, where cancer cells are inherently resistant to treatment, or acquired, where initially sensitive cancer cells develop resistance over time.

Mechanisms of Resistance

Cancer cells can develop resistance to antineoplastic agents through various mechanisms:

Drug Efflux

One of the primary mechanisms is the increased efflux of drugs from cancer cells. This is often mediated by ATP-binding cassette transporters, such as P-glycoprotein, which pump chemotherapeutic agents out of the cells, reducing their intracellular concentrations and effectiveness.

Drug Inactivation

Cancer cells can also develop the ability to inactivate drugs. This can occur through the increased expression of enzymes that metabolize and neutralize the drugs, rendering them ineffective.

Alteration of Drug Targets

Changes in the structure or expression of drug targets can lead to resistance. For example, mutations in the tyrosine kinase domain of the BCR-ABL protein can confer resistance to imatinib in chronic myeloid leukemia.

DNA Repair

Enhanced DNA repair mechanisms can allow cancer cells to survive the DNA-damaging effects of certain chemotherapeutic agents. This includes increased expression of DNA repair enzymes that correct the damage caused by drugs like cisplatin.

Apoptosis Evasion

Cancer cells can evade apoptosis, the programmed cell death that is often triggered by chemotherapy. This can occur through the overexpression of anti-apoptotic proteins such as Bcl-2 or the downregulation of pro-apoptotic factors.

Clinical Implications

Antineoplastic resistance poses a significant challenge in the treatment of cancer. It can lead to treatment failure and disease progression. Understanding the mechanisms of resistance is crucial for developing strategies to overcome it, such as combination therapies that target multiple pathways or the development of new drugs that can bypass resistance mechanisms.

Strategies to Overcome Resistance

Several strategies are being explored to overcome antineoplastic resistance:

Combination Therapy

Using multiple drugs with different mechanisms of action can help prevent or overcome resistance. This approach can target different pathways simultaneously, reducing the likelihood of resistance development.

Targeted Therapy

Targeted therapies are designed to specifically inhibit the molecular pathways that are altered in cancer cells. These therapies can be more effective and less toxic than traditional chemotherapy.

Immunotherapy

Immunotherapy harnesses the body's immune system to fight cancer. It can be effective in cases where traditional chemotherapy fails due to resistance.

Related Pages

• Chemotherapy
• Cancer
• Drug resistance
• Targeted therapy