Investigating New Ovarian Cancer Treatments

Reizes and other researchers are focusing their efforts in the laboratory on developing ways to improve these ovarian cancer medications. "How do we take those known drugs and make them better, make them more effective, improve the lives of our patients," he says.

Preventing Chemotherapy Resistance

Platinum-based chemotherapy drugs like cisplatin (Platinol) and carboplatin (Paraplatin) are part of the standard of care for ovarian cancer. Women get these drugs either before surgery (called neoadjuvant chemotherapy) to shrink the tumor and make it easier to remove, or after surgery to get rid of any cancer cells that remain.

Chemotherapy drugs work very well for a while, but eventually, the cancer becomes resistant to the effects of these drugs and starts to grow again. Researchers like Dr. Reizes want to know why tumors become resistant to chemotherapy drugs, and how they can overcome that resistance.

One method they're investigating is combining other drugs with chemotherapy to make the treatment more effective, and increase the odds that the cancer will respond to it. "We’re finding ways to enhance the ability of these drugs to work, prolong life, and ensure that patients have a high quality of life," he says.

Making PARP Inhibitors Work for More Women

PARP, or poly (ADP-ribose) polymerase inhibitors, are a group of targeted drugs that work against ovarian cancer at the genetic level. When the DNA in a cell breaks, PARP enzymes rush in to mend the damaged strands. PARP inhibitors interrupt that repair process, preventing cancer cells from fixing themselves. Ultimately, the cancer is unable to survive.

PARP inhibitors are particularly effective for women who carry inherited BRCA gene mutations, which themselves make it more difficult for cells to repair their DNA damage. "The combination of having this BRCA inhibitor or mutation and the PARP inhibitor allows for a very effective drug combination," Reizes says. "In some cases you see complete remission."

The problem is that not everyone has these mutations. Only about 5% to 10% of ovarian cancers have an inherited mutation like BRCA. So Reizes and his colleagues are trying to make PARP inhibitors work better across a wider group of women with ovarian cancer by creating what he calls “BRCA-ness.”

Some women with BRCA gene mutations have what's called a homologous recombination deficiency (HRD), which means their ovarian cancer cells have trouble repairing themselves. HRD makes the cancer easier to treat, in effect by helping the PARP inhibitors work more efficiently against it.

However, the American Society of Clinical Oncology (ASCO) released new guidelines recommending PARP inhibitors be offered to women, with or without genetic mutations, who are newly diagnosed with stage III or IV ovarian cancer and have improved with chemotherapy.

At Reizes' lab, he and his fellow researchers have discovered ways to produce a state of HR deficiency in a variety of ovarian cancer cells and tumors. This finding is leading to the development of drugs that inhibit the HR repair mechanisms. Once the cancer has become more vulnerable to treatment, "Now we’re able to come back with a PARP inhibitor and really eliminate the cancer cells," he says.

Many new therapies like the ones Reizes is developing are available to ovarian cancer patients for experimental use in clinical trials. Taking part in one of these studies could give you access to a new, and potentially more effective ovarian cancer treatment. Ask your doctor if any clinical trials currently in progress might be a good fit for you.

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