Cancer Research and Treatment

Efficacy of Chemotherapy Following Prior PARP-Inhibitor Treatment in Patients with Ovarian Cancer: Jung Chul Kim, Junsik Park, Yong Jae Lee, Eun Ji Nam, Sang Wun Kim, Sung-Hoon Kim, Young Tae Kim, Se Ik Kim, Jae-Weon Kim, Byoung-Gie Kim, Jung-Yun Lee; Received December 23, 2024 Accepted March 16, 2025 Published online March 19, 2025; DOI: https://doi.org/10.4143/crt.2024.1202 [Epub ahead of print]

Abstract PDF Supplementary Material PubReader ePub: Purpose
Considering the current lack of consensus on post–poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi) treatment strategies, this study aimed to evaluate the efficacy of subsequent therapy and compare the outcomes of regimes in patients with recurrent ovarian cancer after PARPi treatment.
Materials and Methods
This multi-center retrospective cohort study analyzed data on patients diagnosed with ovarian cancer between January 2012 and June 2023 who had previously used PARPi after first- to fourth-line platinum-based chemotherapy. The primary endpoint was progression-free survival (PFS), which was the interval between recurrence after using PARPi and subsequent recurrence in the case of recurrence.
Results
Of 318 patients, 147/318 (46.2%) recurred after the PARPi maintenance. Patients were categorized into groups based on subsequent therapy except non-treated (11/147, 7.5%): platinum-based chemotherapy (89/147, 60.5%), non-platinum-based chemotherapy (21/147, 14.3%), other treatments (26/147, 17.7%), and the median PFS (mPFS) for each group were 7.3, 4.8, and 11.4 months, respectively. Among the platinum-based chemotherapy group, the gemcitabine+carboplatin regimen demonstrated a longer mPFS (10.1 months) than the other regimens (6.6 months, p=0.019). In non-platinum-based chemotherapy, no statistically significant differences were observed among the regimens. And, in the other therapy group, where the proportion of patients with oligometastasis was as high as 88.5%, no significant differences were observed among the therapies, including other modalities.
Conclusion
In the subsequent chemotherapy of recurrent ovarian cancer after platinum-based chemotherapy and PARPi, the gemcitabine+carboplatin regimen demonstrated a potential to delay recurrence more effectively compared to other therapies.

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Lung and Thoracic cancer

The Synergistic Effect of PARP Inhibitors and Irinotecan in Small Cell Lung Cancer Cells: Songji Oh, Soyeon Kim, Bhumsuk Keam, Jeonghwan Youk, Tae Min Kim, Dong-Wan Kim, Miso Kim; Cancer Res Treat. 2025;57(4):1040-1050. Published online January 7, 2025; DOI: https://doi.org/10.4143/crt.2024.728

Abstract PDF Supplementary Material PubReader ePub: Purpose
This study focused on combining irinotecan with poly(ADP-ribose) polymerase (PARP) inhibitors to explore the potential for novel combination therapeutics in small cell lung cancer (SCLC).
Materials and Methods
We selected 10 different SCLC cell lines with diverse mutational backgrounds in DNA damage response (DDR) pathway genes to evaluate the efficacy of the combination of three PARP inhibitors and irinotecan. After the cells were exposed to the drugs for 7 days, cell viability was measured, and a combination index was calculated. Apoptotic signaling was assessed via western blot, and DNA damage was evaluated using an alkaline comet assay.
Results
We assessed the synergistic effects of PARP inhibitors and irinotecan in in vitro SCLC models, which revealed increased sensitivity, particularly in cells harboring BRCA mutations. However, even in cells lacking mutations in DDR pathway genes, the combination of the two drugs exhibited a synergistic effect. When treated with 50 nM irinotecan, the IC₅₀ fold changes for PARP inhibitors were as follows: olaparib, 1,649±4,049; talazoparib, 25±34.21; venadaparib, 336±596.01. This combination enhanced apoptosis signaling and increased p-chk1 and p-p53 protein levels. Additionally, the treatment of PARP inhibitor with irinotecan increased DNA damage, as visualized by the alkaline comet assay.
Conclusion
This study provides preclinical evidence of the potential clinical benefits of combining irinotecan with PARP inhibitors in SCLC. Further clinical investigations are warranted to validate these findings for the development of more effective and personalized therapeutic strategies for SCLC patients.

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Gynecologic cancer

Time-Trend Analysis and Risk Factors for Niraparib-Induced Nausea and Vomiting in Ovarian Cancer: A Prospective Study: Young Wook Jeong, Dongkyu Eugene Kim, Ji Hyun Kim, Se Ik Kim, Hyeong In Ha, Sang-Yoon Park, Myong Cheol Lim; Cancer Res Treat. 2025;57(3):865-872. Published online November 4, 2024; DOI: https://doi.org/10.4143/crt.2024.899

Abstract PDF Supplementary Material PubReader ePub

Purpose
Nausea and vomiting are major non-hematological adverse events associated with niraparib maintenance therapy. This study aimed to investigate the time-trend patterns of niraparib-induced nausea and vomiting (NINV) and the associated risk factors in patients with ovarian cancer.
Materials and Methods
In this prospective study, we enrolled patients with stage III-IV epithelial ovarian cancer who received niraparib as frontline maintenance therapy. The clinicopathological characteristics and time-trend patterns of patients with NINV were collected through in-person surveys and electronic medical records from the National Cancer Center.
Results
Of 53 patients, 50 (94.3%) were diagnosed with high-grade serous ovarian carcinoma. BRCA mutations and homologous recombination deficiency (HRD) were identifi ed in 23 (43.4%) and 32 (60.4%) patients, respectively. Thirty-one patients (58.5%) had NINV. Time-trend analyses revealed that the fi rst peak intensity of NINV was reached at 3 h post-dose, and the second peak intensity was reached at 11 hour post-dose. NINV signifi cantly decreased from week 1 to weeks 8 and 12. In multivariate analyses of risk factors for NINV, HRD-positive tumors (p < 0.001) and prior experience of chemotherapy-induced nausea and vomiting (p=0.004) were associated with the occurrence of NINV.
Conclusion
Pre-emptive treatment with antiemetics is required to manage early-phase NINV during niraparib maintenance therapy in patients with risk factors. Additional larger studies are needed to confi rm these fi ndings and to develop optimal preventive strategies for NINV.

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Niraparib

Reactions Weekly.2025; 2076(1): 354. CrossRef

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Recent Advances in Genomic Approaches for the Detection of Homologous Recombination Deficiency: Yoo-Na Kim, Doga C. Gulhan, Hu Jin, Dominik Glodzik, Peter J. Park; Cancer Res Treat. 2024;56(4):975-990. Published online July 17, 2024; DOI: https://doi.org/10.4143/crt.2024.154

Abstract PDF PubReader ePub

Accurate detection of homologous recombination deficiency (HRD) in cancer patients is paramount in clinical applications, as HRD confers sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors. With the advances in genome sequencing technology, mutational profiling on a genome-wide scale has become readily accessible, and our knowledge of the genomic consequences of HRD has been greatly expanded and refined. Here, we review the recent advances in HRD detection methods. We examine the copy number and structural alterations that often accompany the genome instability that results from HRD, describe the advantages of mutational signature-based methods that do not rely on specific gene mutations, and review some of the existing algorithms used for HRD detection. We also discuss the choice of sequencing platforms (panel, exome, or whole-genome) and catalog the HRD detection assays used in key PARP inhibitor trials.

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Recommendations for Clinical Molecular Laboratories for Detection of Homologous Recombination Deficiency in Cancer
Susan J. Hsiao, Destin Black, Kelly A. Devereaux, Ian S. Hagemann, Lawrence J. Jennings, Diana Mandelker, Vera A. Paulson, Michelle Shiller, Tracy L. Stockley, Eric Vail, Praveen Vikas, Anna Yemelyanova
The Journal of Molecular Diagnostics.2025; 27(8): 685. CrossRef
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Mi-Ran Ki, Dong Hyun Kim, Mohamed A. A. Abdelhamid, Seung Pil Pack
Biosensors.2025; 15(11): 737. CrossRef

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Gastrointestinal cancer

Inhibition of WEE1 Potentiates Sensitivity to PARP Inhibitor in Biliary Tract Cancer: Hye-Rim Seo, Ah-Rong Nam, Ju-Hee Bang, Kyoung-Seok Oh, Jae-Min Kim, Jeesun Yoon, Tae-Yong Kim, Do-Youn Oh; Cancer Res Treat. 2022;54(2):541-553. Published online August 6, 2021; DOI: https://doi.org/10.4143/crt.2021.473

Abstract PDF PubReader ePub

Purpose
Up to 20% of patients with biliary tract cancer (BTC) have alterations in DNA damage response (DDR) genes, including homologous recombination (HR) genes. Therefore, the DDR pathway could be a promising target for new drug development in BTC. We aim to investigate the anti-tumor effects using poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors in BTC.
Materials and Methods
We used 10 BTC cell lines to evaluate an anti-tumor effect of olaparib (a PARP inhibitor) and AZD1775 (a WEE1 inhibitor) in in vitro. Additionally, we established SNU869 xenograft model for in vivo experiments.
Results
In this study, we observed a modest anti-proliferative effect of olaparib. DNA double-strand break (DSB) and apoptosis were increased by olaparib in BTC cells. However, olaparib-induced DNA DSB was repaired through the HR pathway, and G2 arrest was induced to secure the time for repair. As AZD1775 typically regulates the G2/M checkpoint, we combined olaparib with AZD1775 to abrogate G2 arrest. We observed that AZD1775 downregulated p-CDK1, a G2/M cell cycle checkpoint protein, and induced early mitotic entry. AZD1775 also decreased CtIP and RAD51 expression and disrupted HR repair. In xenograft model, olaparib plus AZD1775 treatment reduced tumor growth more potently than did monotherapy with either drug.
Conclusion
This is the first study to suggest that olaparib combined with AZD1775 can induce synergistic anti-tumor effects against BTC. Combination therapy that blocks dual PARP and WEE1 has the potential to be further clinically developed for BTC patients.

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Yijun Xie, Di Xiao, Duo Li, Mei Peng, Wei Peng, Huaxin Duan, Xiaoping Yang
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Targeted Therapy of HPV Positive and Negative Tonsillar Squamous Cell Carcinoma Cell Lines Reveals Synergy between CDK4/6, PI3K and Sometimes FGFR Inhibitors, but Rarely between PARP and WEE1 Inhibitors
Ourania N. Kostopoulou, Mark Zupancic, Mariona Pont, Emma Papin, Monika Lukoseviciute, Borja Agirre Mikelarena, Stefan Holzhauser, Tina Dalianis
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