The mechanism of cancer cell death by PARP inhibitors goes beyond DNA damage alone

Macciò, Antonio; Madeddu, Clelia

doi:10.1002/ijc.32392

Cited by 6 publications

(7 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Therefore, it is reasonable to hypothesize that these unique glucose metabolism characteristics of neoplastic cells, which could be induced by the same mediators that lead immune cells to become M1 TAMs, as well as the associated M1-induced functional iron deficiency 2 , might cause M1-enriched tumors to be more sensitive to chemotherapy regimens. As we stated in our review on the mechanism of action of cisplatin 10 and re-emphasized in our recent analysis (commentary) on the efficacy of poly(ADP-ribose) polymerase inhibitors 11 , cancer cell metabolism based on an efficient Warburg effect is fundamental for the effectiveness of the antineoplastic actions www.nature.com/scientificreports www.nature.com/scientificreports/ of these drugs. It is worth noting here that in cancers that do not display the Warburg effect, such as in positron emission tomography-negative tumors, cisplatin is ineffective 10 .…”

Section: Discussionmentioning

confidence: 82%

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Macciò

Gramignano²,

Cherchi

et al. 2020

Sci Rep

Self Cite

120

View full text Add to dashboard Cite

The identification of prognostic and predictive markers is crucial for choosing the most appropriate management method for ovarian cancer patients. We aimed to assess the prognostic role of tumorassociated macrophage (TAM) polarization in advanced ovarian cancer patients. We carried out a prospective observational study that included 140 consecutive patients with advanced-stage highgrade serous ovarian cancer as well as patients with other histotypes of ovarian cancer and patients with ovarian metastasis from other sites between June 2013 and December 2018. Patients were enrolled at the time of laparoscopic surgery before receiving any antineoplastic treatment. We found that patients with high-grade serous papillary ovarian cancers had a prevalence of M1 TAMs, a higher M1/M2 ratio, and a longer overall survival (OS) and progression-free survival (PFS) than other patients. Regression analysis confirmed that there was a significant positive association between the M1/M2 ratio and an improved OS, PFS and platinum-free interval (PFI), both in the entire population and in patients stratified according to tumor type and initial surgery. Kaplan-Meier analysis was performed after the patients were divided into 2 groups according to the median M1/M2 ratio and revealed that patients with a high M1/M2 ratio had a higher OS, PFS and PFI than those with a low M1/M2 ratio. In conclusion, the prognostic and predictive role of TAM polarization in the tumor microenvironment could be of great clinical relevance and may allow the early identification of patients who are likely to respond to therapy. Further studies in a larger prospective sample are warranted.www.nature.com/scientificreports www.nature.com/scientificreports/ linear relationship (β coefficient = 0.504, 95% CI 0.493-10.334, p = 0.033) was found between the platinum-free interval and M1/M2 ratio (Fig. 2).The median value for the M1/M2 ratio was 1.4. Then, we analyzed the difference in OS and PFS by Kaplan-Meier curve analysis and log-rank analysis between patients with an M1/M2 ratio ≥ 1.4 and those with an M1/M2 ratio < 1.4. We found that patients with an M1/M2 ratio ≥ 1.4 had a significantly longer OS (34 months versus 18 months, HR 2.7483, 95% CI: 1.1667-6.4736; p = 0.0207), PFS (24 months versus 9 months, HR 2.1285, 95% CI: 1.0461-4.3309; p = 0.0371) and PFI (12 months versus 6 months, HR 3.3959, 95% CI 1.2471-9.2469; p = 0.0168) ( Fig. 3). Scientific RepoRtS |(2020) 10:6096 | https://doi.

show abstract

Section: Discussionmentioning

confidence: 82%

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Macciò

Gramignano²,

Cherchi

et al. 2020

Sci Rep

Self Cite

120

View full text Add to dashboard Cite

show abstract

“…In one recent meta-analysis studying the efficacy of PARPi in newly diagnosed ovarian cancer, a significant clinical benefit of PARPi has been obtained both in Non-BRCA mutated patients and in patients even without homologous recombination deficiency (48). In fact, besides DNA damage-induced cell death, PARP inhibitors, by inhibiting the PARP-1, can alter cellular energy metabolism and redox balance, leading to cancer cell apoptosis (49). Unlike BRCA2, which directly guided RAD51 to damage sites in the process of DNA repair, BRCA1 plays more diverse roles.…”

Section: Discussionmentioning

confidence: 99%

BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

Dai

et al. 2021

Front. Oncol.

View full text Add to dashboard Cite

BackgroundBRCA2 mutation has a more substantial impact on the homologous recombination and superior therapeutic response to platinum-based chemotherapy than BRCA1 mutation. Whether BRCA2-mutated patients could benefit more from PARPi than BRCA1-mutated patients remains unclear. We performed a meta-analysis to assess the efficacy difference of PARPi between BRCA1 mutation carriers and BRCA2 mutation carriers.MethodsPubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) of PARPi that had available hazard ratios (HRs) of progression-free survival (PFS) in both BRCA1-mutated population and BRCA2-mutated population. We calculated the pooled PFS HRs and 95%CI using randomized-effect models, and the difference between the two estimates was compared by interaction test.ResultsA total of 11 eligible RCTs of high quality were identified through search. Overall, 1544 BRCA1 mutation carriers and 1191 BRCA2 mutation carriers were included in the final analysis. The pooled PFS HR was 0.42 (95% CI: 0.35-0.50) in BRCA1-mutated patients who were treated with PARPi compared with patients in the control group. In BRCA2-mutated patients treated with PARPi, the pooled PFS HR compared with the control groups was 0.35 (95% CI: 0.24-0.51). The difference in efficacy of PARPi was not significant between the two subgroups (Pheterogeneity = 0.40, for interaction).ConclusionBRCA1-mutated patients and BRCA2-mutated patients could benefit from PARPi, and the efficacy is comparable. Currently, there is no evidence that BRCA2-mutated patients would benefit more from PARPi than BRCA1-mutated patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/, identifier CRD42020214582.

show abstract

“…PARP causes DNA repair, and CHOP upregulates ER stress with the acidic vacuole compartment leading to an imbalance of cellular homeostasis of the tumor microenvironment. [49][50][51][52] In this study, CCS NPs showed more DNA bond breakage that induced more endogenous protein exploitation. The green fluorescence (Fig.…”

Section: Immunofluorescencementioning

confidence: 59%

Camptothecin loaded casein nanosystem for tuning the therapeutic efficacy against highly metastatic triple-negative breast cancer cells

et al. 2023

View full text Add to dashboard Cite

show abstract

The mechanism of cancer cell death by PARP inhibitors goes beyond DNA damage alone

Cited by 6 publications

References 11 publications

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

Role of M1-polarized tumor-associated macrophages in the prognosis of advanced ovarian cancer patients

BRCA1 Versus BRCA2 and PARP Inhibitors Efficacy in Solid Tumors:A Meta-Analysis of Randomized Controlled Trials

Camptothecin loaded casein nanosystem for tuning the therapeutic efficacy against highly metastatic triple-negative breast cancer cells

Contact Info

Product

Resources

About