EZH2 inhibitors and PARP inhibitors are two classes of drugs that are used in the treatment of cancer. Both classes of drugs target specific enzymes that play key roles in cancer progression and development. In this answer, we will discuss the differences between EZH2 inhibitors and PARP inhibitors, including their mechanisms of action, clinical uses, and potential side effects.
EZH2 Inhibitors:
EZH2 (Enhancer of Zeste Homolog 2) is a histone methyltransferase that is involved in the regulation of gene expression. It plays a critical role in the formation of the polycomb repressive complex 2 (PRC2), which functions to silence the expression of genes involved in cell differentiation and tumor suppression. EZH2 is frequently overexpressed in a variety of cancers, including breast, prostate, and lung cancers, and is associated with poor prognosis.
EZH2 inhibitors are a class of drugs that target EZH2, preventing its function as a histone methyltransferase. This leads to the activation of tumor-suppressive genes and the inhibition of cancer cell growth. Several EZH2 inhibitors have been developed and are currently being tested in clinical trials for the treatment of various types of cancer, including lymphoma, leukemia, and solid tumors.
Clinical Uses:
EZH2 inhibitors have shown promising results in preclinical and early clinical studies for the treatment of cancer. In particular, they have shown efficacy in the treatment of lymphoma, which is frequently associated with overexpression of EZH2. Two EZH2 inhibitors, tazemetostat and CPI-1205, have been approved by the FDA for the treatment of relapsed or refractory follicular lymphoma and epithelioid sarcoma, respectively.
Potential Side Effects:
The most common side effects of EZH2 inhibitors include fatigue, nausea, anemia, decreased appetite, and constipation. Less common side effects include liver toxicity, cardiac toxicity, and secondary malignancies.
PARP Inhibitors:
PARP (Poly ADP-Ribose Polymerase) is an enzyme that plays a critical role in DNA repair. It is involved in the repair of single-strand DNA breaks through the base excision repair (BER) pathway. PARP inhibitors are a class of drugs that target PARP, preventing its function in DNA repair. This leads to the accumulation of DNA damage and the induction of cell death in cancer cells.
PARP inhibitors have been approved by the FDA for the treatment of ovarian and breast cancers that have BRCA mutations. BRCA mutations are associated with defects in DNA repair, and PARP inhibitors have been shown to be particularly effective in these types of tumors.
Clinical Uses:
PARP inhibitors have shown promising results in the treatment of ovarian and breast cancers, particularly in patients with BRCA mutations. Three PARP inhibitors, olaparib, rucaparib, and niraparib, have been approved by the FDA for the treatment of ovarian cancer. Two PARP inhibitors, olaparib and talazoparib, have been approved for the treatment of breast cancer.
PARP inhibitors are also being investigated in clinical trials for the treatment of other types of cancer, including pancreatic, prostate, and lung cancers.
Potential Side Effects:
The most common side effects of PARP inhibitors include fatigue, nausea, vomiting, anemia, and diarrhea. Less common side effects include myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), and secondary malignancies.
Differences between EZH2 inhibitors and PARP inhibitors:
Mechanism of Action:
EZH2 inhibitors target EZH2, preventing its function as a histone methyltransferase. This leads to the activation of tumor-suppressive genes and the inhibition of cancer cell growth.
PARP inhibitors target PARP, preventing its function in DNA repair. This leads to the accumulation of DNA damage and the induction of cell death in cancer cells.
Clinical Uses:
EZH2 inhibitors are being investigated for the treatment of lymphoma, leukemia, and solid tumors.
PARP inhibitors are approved for the treatment of ovarian and breast cancers that have BRCA mutations, and are being investigated for the treatment of other types of cancer.
Side Effects:
The most common side effects of both EZH2 inhibitors and PARP inhibitors are fatigue, nausea, and anemia. However, the less common side effects differ between the two classes of drugs. EZH2 inhibitors have been associated with liver toxicity, cardiac toxicity, and secondary malignancies, while PARP inhibitors have been associated with MDS, AML, and secondary malignancies.
In conclusion, EZH2 inhibitors and PARP inhibitors are two classes of drugs that target specific enzymes involved in cancer progression and development. While both classes of drugs have shown promise in the treatment of cancer, they differ in their mechanisms of action, clinical uses, and potential side effects. It is important that patients and healthcare providers work together to determine the best treatment options based on individual patient characteristics and tumor biology.
