Rationale for combination PARP inhibitor and antiangiogenic treatment in advanced epithelial ovarian cancer: A review

Secord, Angeles Alvarez; O’Malley, David M.; Sood, Anil K.; Westin, Shannon N.; Liu, Joyce F.

doi:10.1016/j.ygyno.2021.05.018

Cited by 34 publications

(24 citation statements)

References 66 publications

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“…In an effort to address this issues, several trials focused on specific tyrosine kinase inhibitors with some of them demonstrating activity against VEGFR [ 57 ]. Antiangiogenic drugs have been studied extensively as an addition to the chemotherapy backbone [ 58 ], but a clear benefit was seen only in a high risk patient population [ 59 ], however novel combinations are under way in order to augment their therapeutic potential in combination with immunotherapy [ 60 ] or PARPi [ 61 ]. In addition, the combination of PARPi with immunotherapy could be synergistic and is under evaluations in recent clinical trials [ 62 ].…”

Section: Discussionmentioning

confidence: 99%

Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present

et al. 2022

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Ovarian cancer is composed of a complex system of cells best described by features such as clonal evolution, spatial and temporal genetic heterogeneity, and development of drug resistance, thus making it the most lethal gynecologic cancer. Seminal work on cancer as an evolutionary process has a long history; however, recent cost-effective large-scale molecular profiling has started to provide novel insights coupled with the development of mathematical algorithms. In the current review, we have systematically searched for articles that focused on the clonal evolution of ovarian cancer to offer the whole landscape of research that has been done and highlight future research avenues given its characteristic features and connections to evolutionary biology.

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Section: Discussionmentioning

confidence: 99%

Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present

et al. 2022

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“…Combinations of PARP inhibitors and anti-angiogenic agents have been tested in epithelial ovarian cancer, where these compounds proved to be effective as monotherapy [ 102 ]. Early phase trials combining these classes of drugs have been conducted even in other tumor types, such as breast and pancreatic cancer [ 103 , 104 ].…”

Section: Combination Regimensmentioning

confidence: 99%

“…The simultaneous use of PARP and angiogenesis inhibitors seem to exert a synergistic effect. Indeed, anti-angiogenics-induced hypoxia might impair homologous recombination functioning, while PARP inhibition seems to affect tumor angiogenesis [ 102 , 105 ]. Additionally, these agents present limited overlapping toxicities as confirmed by randomized trials, further fostering their development in combination regimens ( Table 3 ).…”

Section: Combination Regimensmentioning

confidence: 99%

Everything Comes with a Price: The Toxicity Profile of DNA-Damage Response Targeting Agents

Martorana

Silva

Sessa

et al. 2022

Cancers

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Targeting the inherent vulnerability of cancer cells with an impaired DNA Damage Repair (DDR) machinery, Poly-ADP-Ribose-Polymerase (PARP) inhibitors have yielded significant results in several tumor types, eventually entering clinical practice for the treatment of ovarian, breast, pancreatic and prostate cancer. More recently, inhibitors of other key components of DNA repair, such as ATR, CHK1 and WEE1, have been developed and are currently under investigation in clinical trials. The inhibition of DDR inevitably induces on-target and off-target adverse events. Hematological and gastrointestinal toxicities as well as fatigue are common with all DDR-targeting agents, while other adverse events are drug specific, such as hypertension with niraparib and transaminase elevation with rucaparib. Cases of pneumonitis and secondary hematological malignancies have been reported with PARP inhibitors and, despite being overly rare, they deserve particular attention due to their severity. Safety also represents a crucial issue for the development of combination regimens incorporating DDR-targeting agents with other treatments, such as chemotherapy, anti-angiogenics or immunotherapy. As such, overlapping and cumulative toxicities should be considered, especially when more than two classes of drugs are combined. Here, we review the safety profile of DDR-targeting agents when used as single agents or in combination and we provide principles of toxicity management.

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“…In addition to antiangiogenic agents, PARPi was combined with other targeted immunotherapies, such as PD-1/PD-L1 inhibitors, WEE-1 inhibitors, ataxia-telangiectasia-mutated-and-Rad3-related kinase (ATR) inhibitors, MEK inhibitors, and so on ( 37 ). Plenty of studies regarding PARPi and PD-1/PD-L1 combinational therapy are completed or ongoing.…”

Section: Targeting Dna Repair-based Combination Immunotherapiesmentioning

confidence: 99%

“…Although the majority of people initially respond to platinum-based chemotherapy, most patients would suffer a recurrence within 5 years. Currently, most clinical studies regarding immunotherapies are applied to patients who previously received chemotherapy, as we discussed before ( 37 ). Resistance to platinum agents and PARP inhibitors is one of the main obstacles to ovarian cancer therapy ( 155 ).…”

Section: Chemotherapy-based Combination Immunotherapiesmentioning

confidence: 99%

Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed

Bian

Zhao

2022

Front. Immunol.

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Ovarian cancer, one of the most common gynecological malignancies, is characterized by high mortality and poor prognosis. Cytoreductive surgery and chemotherapy remain the mainstay of ovarian cancer treatment, and most women experience recurrence after standard care therapies. There is compelling evidence that ovarian cancer is an immunogenic tumor. For example, the accumulation of tumor-infiltrating lymphocytes is associated with increased survival, while increases in immunosuppressive regulatory T cells are correlated with poor clinical outcomes. Therefore, immunotherapies targeting components of the tumor microenvironment have been gradually integrated into the existing treatment options, including immune checkpoint blockade, adoptive cell therapy, and cancer vaccines. Immunotherapies have changed guidelines for maintenance treatment and established a new paradigm in ovarian cancer treatment. Despite single immunotherapies targeting DNA repair mechanisms, immune checkpoints, and angiogenesis bringing inspiring efficacy, only a subset of patients can benefit much from it. Thus, the multi-immunotherapy investigation remains an active area for ovarian cancer treatment. The current review provides an overview of various clinically oriented forms of multi-immunotherapy and explores potentially effective combinational therapies for ovarian cancer.

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Rationale for combination PARP inhibitor and antiangiogenic treatment in advanced epithelial ovarian cancer: A review

Cited by 34 publications

References 66 publications

Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present

Evolutionary perspectives, heterogeneity and ovarian cancer: a complicated tale from past to present

Everything Comes with a Price: The Toxicity Profile of DNA-Damage Response Targeting Agents

Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed

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