PARP Inhibitors For Cancer: Risks And Side Effects 

Researchers have come up with different treatment options for cancers. And one of these is PARP inhibitors. 

The acronym “PARP” stands for poly adenosine diphosphate-ribose polymerase which is the name of an enzyme present in the human body.

PARP inhibitor drugs are an effective new class of anticancer drugs.

What Is A PARP Inhibitor?

The very enzyme PARP (PARP1 and 2) is responsible for helping in DNA damage repair to the cells. 

Thus, PARP inhibitor drugs work by preventing the cancer cell from repairing. 

This, therefore, results in the death of the cancerous cells. 

Targeted Cancer Therapy 

Killer cancers require extreme care and attention. 

So this is why healthcare providers employ targeted cancer therapies. 

Such therapies interfere with specific proteins involved in tumor formation.

Studies have identified PARP inhibitor drugs can be as effective drugs in targeted therapy for cancer. 

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Main PARP Inhibitors

The most common and main types of PARP inhibitors include:

• Talazoparib 
• Rucaparib 
• Olaparib 
• Niraparib 

How Do They work?

As the name indicates, PARP inhibitors inhibit the activity of PARP enzymes. 

This anti-cancer treatment is effective and uses a process we call synthetic lethality. 

It is defined as a type of genetic interaction where there is the occurrence of two genetic events simultaneously. 

This co-occurrence results in cancer cell death.

Moreover, research shows that PARP inhibitor treatment takes advantage of synthetic lethality and induces cell death by exploiting a defect in DNA repair. 

PARP inhibitors are most effective against tumors arising in patients with germline mutation. 

This is because they have a specific type of DNA repair defect which the drug exploits. 

The drugs can work effectively in combination with other treatment modalities and medications such as temozolomide.

How PARP inhibitors Manage Cancer

PARP inhibitors carry out synthetic lethality in cancers where there are susceptibility proteins i.e. BRCA 1 and BRCA2. 

These drugs then hamper the base excision repair (BER) that is important for the overall survival of the cancerous cells. 

This and other deficiencies in the HR pathway then lead to tumor cell death.

Similarly, PTEN-deficient cancerous cells are more sensitive to PARP inhibitors. 

When managing cancer, we can use PARP inhibitor treatment as single agents or in combination with other anti-cancer therapies.

As Single Agents

PARP inhibitors kill BRCA-2 deficient cells as single agents and are more potent (3 times) than cisplatin cytotoxicity.

In Combination With Cytotoxic Therapy 

We can use PARP inhibitors with DNA methylating agents such as temozolomide. 

Moreover, a study suggests that a superior anti-cancer effect is achieved with the combination of PARP inhibitor and temozolomide in the management of Ewing’s sarcoma.

In Combination With Ionizing Radiation 

The efficacious drug PARP inhibitor effectively potentiates ionizing radiation via the inhibition of BER. 

According to a study, we can achieve a great anti-cancer effect when pairing radiotherapy (XRT) with PARP-1 inhibitors. 

Types Of Cancer That PARP Inhibitors Can Work For

Breast Cancer 

PARP inhibition was found to be a promising strategy in the treatment of breast cancers that are associated with BRCA mutation 1/2. 

The treatment method is also effective in curing papillary serous ovarian cancers. 

A study validates the use of PARP inhibitors as adjuvant therapy in the treatment of breast cancer.

Ovarian Cancer 

Ovarian cancer is a leading killer in women. 

It is fifth in cancer deaths among women. 

Further, PARP inhibitors are flag-bearers of change in the management of ovarian cancer. 

This type of drug is pretty effective as a therapeutic agent by inducing synthetic lethality in ovarian cancer. 

FDA/EMA approved PARP inhibitors for ovarian cancer include:

• Olaparib 
• Rucaparib 
• Niraparib 

Keeping in mind the efficacy of PARP inhibitors, these are being launched for newly diagnosed germline BRCA cancers and platinum-sensitive recurrent ovarian cancer. 

PARP inhibitors show promising activity against BRCA mutated ovarian cancer. 

Rucaprib can be advantageous in the treatment of a variety of cancers including:

• Ovarian 
• Peritoneal 
• Fallopian tube 
• Prostate 

Pancreatic Cancer 

BRCA associated pancreatic cancer can be effectively managed using PARP inhibitors, as suggested by a study. 

It is considered to be more beneficial as compared to chemotherapy for this type of cancer. 

It has evolved as a new therapeutic opportunity. 

Research suggests that radiochemotherapy can be better optimized using PARP inhibitors in the treatment of pancreatic cancer. 

The drugs are considered effective chemo-radiosensitizers, which therefore means that giving PARP inhibitors to cancer patients increases their sensitivity to chemotherapy and radiotherapy for cancer treatments.

Prostate Cancer 

These drugs seem to help in the management of prostate cancer as well. 

Studies suggest that we can achieve far better results when we pair PARP therapy with chemo-, radio-, and hormonal therapies, etc.

Furthermore, as per a 2019 study, targeting the DNA repair pathway can render prostate cancer inactive and weak to survive. 

Nicaparib is not very effective for prostate cancer. 

Moreover, other types of cancers for which PARP inhibitors are good for usage include:

• Peritoneal cancer
• Fallopian tube cancer

Do PARP Inhibitors Affect Normal Cells?

The most important question about any anti-cancer drug is if it affects normal cells.

Anti-cancer drugs that do not affect the normal cells are recommended. 

Olaparib is an FDA-approved PARP inhibitor therapy that is indicated in the treatment of patients suffering from breast cancer, prostate cancer, and lung cancer. 

PARP inhibitor therapy does not seem to affect normal, non-cancerous cells. 

As cancerous cells grow and multiply quickly compared to normal cells, PARP inhibitors only target the abnormally multiplying cells.

Risks And Side Effects 

All PARP inhibitors seem to have the following side effects:

• A loss of appetite 
• Changes in taste sensation
• Nausea 
• Vomiting 
• Diarrhea 
• Fatigue 
• Stomach ache and indigestion
• Muscles and joint aches 
• Lethargy and fatigue
• Headaches 
• Dizziness 
• Increased risk of infection and bleeding 

Further, a study suggests that toxicities induced by a PARP inhibitor can be managed with supportive care and dose reduction. 

However, your healthcare provider must give you appropriate counseling before the start of the treatment.

What To Discuss With Your Doctor

As already mentioned, counseling before the beginning of the treatment is crucial. Therefore, you must gain appropriate knowledge pre-hand. 

You must ask your doctor about the following points:

• Possible side effects and drug interactions  
• Management of side effects 
• Risks involved with the therapy
• And effectiveness of the treatment (how it has helped other patients)

You should also inform your doctor about any other medications, and remedies used to make sure that it doesn’t interfere with the treatment.

Conclusion 

So, PARP inhibitors are specialized anti-cancer drugs that target the PARP enzyme in the body. 

This enzyme is responsible for repairing the DNA damage to cancer cells. Abstinence of enzymatic action means tumor cell death. 

Moreover, the most common drugs are rucaparib, olaparib, talazoparib and niraparib. 

These drugs are most effective against BRCA mutation cancers such as ovarian, fallopian tube, peritoneal, breast, and prostate cancer. 

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