**5. Future directions in improving patents care outcomes**

### **5.1 Epigenetics and immunotherapy**

There is biologic plausibility that epigenetic therapies can prime tumors for a better response to immunotherapy and turn "cold" tumors into "hot" ones [68]. For example, in one murine model, the combination of decitabine and anti-CTLA-4 significantly shrunk tumors and prolonged survival as compared to either agent alone [77]. There is additional preclinical data suggesting that AZA can upregulate T-cells in murine models [78]. Additionally, two clinical trials are currently underway. The results from one study of 75 patients are expected in March 2022 (NCT03206047). Its investigators are looking at AZA and atezolizumab with or without the anti-NY-ESO-1 vaccine (a biologic agent) in women with recurrent platinum resistant ovarian cancer. The other study is looking at guadecitabine with pembrolizumab for

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*Novel Indications of Epigenetic Therapy in Ovarian Cancer*

medicine and the targeting of actionable mutations.

**6. Conclusion**

ian cancer.

**Acknowledgements**

**Conflict of interest**

Foundation - Pink Roses Teal Magnolias.

The authors declare no conflict of interest.

in this latter study and results are expected in March 2022.

recurrent ovarian cancer (NCT02901899). Thirty-five patients have been enrolled

The heterogeneity of ovarian cancer is such that no two tumors are alike, however, tumors expressing similar genetic profiles, have been shown to respond to agents targeting their specific genetics. Recent clinical trials indicate that ovarian cancer patients with homologous recombination deficiency, for example, respond well to PARP inhibition [79, 80]. Newer epigenetic therapies like BET inhibitors, have the ability enhance PARP inhibition [69]. Another clinical challenge in ovarian cancer is the *ARID1A* mutation. Ovarian cancers with this mutation are associated with late-stage disease at diagnosis and early recurrence [81]. Roughly 50 percent of clear cell carcinomas, which are notoriously chemoresistant, harbor this mutation. In one murine model, the HDACi vorinostat was found to be highly effective against ARID1A mutated ovarian cancer [81]. Thus, epigenetics may help further precision

Platinum resistant and recurrent ovarian cancer patients have very little in the way of highly effective treatment. Chemotherapy may be effective for a period of months or a few years for these patients, but it is rarely if ever curable. Epigenetic therapies hold promise, especially in conjunction with other mechanisms, like PARP inhibitors and immunotherapy, but the timing, dosing and patient selection must be fine-tuned before they can enter the mainstream of treatment for ovar-

This work has been funded by The Research Initiative Grant, Camden Health

Research Program and Research Grant, The Cooper MD Anderson Cancer

*DOI: http://dx.doi.org/10.5772/intechopen.98187*

**5.2 Epigenetics and precision medicine**

recurrent ovarian cancer (NCT02901899). Thirty-five patients have been enrolled in this latter study and results are expected in March 2022.
