UNASSIGNED: Pre-clinical studies showed the anti-tumor mechanisms of PARP inhibitors (PARPi) and platinum have some crossover and overlap in the DNA damage repair pathway, patients who respond to platinum-based chemotherapy are also more likely to be sensitive to PARPi. This real-world study mainly aimed to evaluate whether TRAE (treatment-related adverse event) between platinum based chemotherapy (PBC) and niraparib are also associated.
UNASSIGNED: Patients received niraparib as maintenance treatment or salvage therapy for advanced ovarian cancer at the First Affiliated Hospital of Gannan Medical University from January 2020 to August 2023 were included. Survival data of niraparib treatment and adverse events occurred during the last platinum-based chemotherapy cycle before starting niraparib treatment and during niraparib treatment are documented. Fisher\'s exact test were used for correlation analysis.
UNASSIGNED: 1. 40 patients treated with niraparib were included in the analysis, including 31 patients treated with niraparib for 1st-line maintenance therapy, 6 patients for PSR (platinum-sensitive recurrence) maintenance therapy, and 3 patients for salvage therapy. The overall median follow-up time was 15.0 months (ranged from 2.2 months to 32.1 months). 2. Overall grade≥3 TRAE (40% vs 70%, p=0.012) including anemia (20% vs 45%, p=0.041) and neutrophil count decreased (17.5% vs 57.5%, p<0.001) was significantly lower during niraparib treatment compared to during chemotherapy. 3. Any grade TRAE (75% vs 100%, p=0.002) including white blood cell count decreased (47.5% vs 87.5%, p<0.001), red blood cell count decreased (57.5% vs 92.5%, p<0.001), anemia (55% vs 87.5%, p<0.001) and neutrophil count decreased (35% vs 85%, p<0.001) were also significantly lower in niraparib treatment group compared with chemotherapy group. No new safety signals were identified.
UNASSIGNED: 1. In this real-world practice, we observed that patients with advanced ovarian cancer who experienced any grade and grade ≥3 TRAE during chemotherapy were well tolerated when treated with niraparib, particularly the incidence of any grade and grade ≥3 anemia, and neutrophil count decreased during niraparib treatment were significantly lower compared with that during chemotherapy. 2. For patients with ovarian cancer who have experienced grade ≥3 hematological adverse reactions during prior platinum-based chemotherapy, greater attention should be paid to the monitoring and management of hematological adverse reactions during subsequent treatment with niraparib.

OBJECTIVE: Platinum-based drugs are cytotoxic drugs commonly used in cancer treatment. They cause DNA damage, effects of which on chromatin and cellular responses are relatively well described. Yet, the nuclear stress responses related to RNA processing are incompletely known and may be relevant for the heterogeneity with which cancer cells respond to these drugs. Here, we determine the type and extent of nuclear stress responses of prostate cancer cells to clinically relevant platinum drugs.
METHODS: We study nucleolar and Cajal body (CB) responses to cisplatin, carboplatin, and oxaliplatin with immunofluorescence-based methods in prostate cancer cells. We utilize organelle-specific markers NPM, Fibrillarin, Coilin, and SMN1, and study CB-regulatory proteins FUS and TDP-43 using siRNA-mediated downregulation.
RESULTS: Different types of prostate cancer cells have different sensitivities to platinum drugs. With equally cytotoxic doses, cisplatin, and oxaliplatin induce prominent nucleolar and CB stress responses while the nuclear stress phenotypes to carboplatin are milder. We find that Coilin is a stress-specific marker for platinum drug response heterogeneity. We also find that CB-associated, stress-responsive RNA binding proteins FUS and TDP-43 control Coilin and CB biology in prostate cancer cells and, further, that TDP-43 is associated with stress-responsive CBs in prostate cancer cells.
CONCLUSIONS: Our findings provide insight into the heterologous responses of prostate cancer cells to different platinum drug treatments and indicate Coilin and TDP-43 as stress mediators in the varied outcomes. These results help understand cancer drug responses at a cellular level and have implications in tackling heterogeneity in cancer treatment outcomes.

The therapeutic advantages of some platinum complexes as major anticancer chemotherapeutic agents and of nucleoside analogue-based compounds as essential antiviral/antitumor drugs are widely recognized. Red blood cells (RBCs) offer a potential new strategy for the targeted release of therapeutic agents due to their biocompatibility, which can protect loaded drugs from inactivation in the blood, thus improving biodistribution. In this study, we evaluated the feasibility of loading model nucleobase-containing Pt(II) complexes into human RBCs that were highly stabilized by four N-donors and susceptible to further modification for possible antitumor/antiviral applications. Specifically, platinum-based nucleoside derivatives [PtII(dien)(N7-Guo)]2+, [PtII(dien)(N7-dGuo)]2+, and [PtII(dien)(N7-dGTP)] (dien = diethylenetriamine; Guo = guanosine; dGuo = 2\'-deoxy-guanosine; dGTP = 5\'-(2\'-deoxy)-guanosine-triphosphate) were investigated. These Pt(II) complexes were demonstrated to be stable species suitable for incorporation into RBCs. This result opens avenues for the possible incorporation of other metalated nucleobases analogues, with potential antitumor and/or antiviral activity, into RBCs.

High mobility group box 1 (HMGB1) is secreted from activated immune cells, necrotic cells, and certain cancers. Previous studies have reported that different patterns of post-translational modification, particularly acetylation and oxidation, mediate HMGB1 release and confer distinct extracellular HMGB1 signaling activity. Here we report that cisplatin but not carboplatin induces secretion of HMGB1 from human A549 non-small cell lung cancer (NSCLC) cells. Cisplatin-mediated HMGB1 secretion was dose-dependent and was regulated by nuclear exportin 1 (XPO1) also known as chromosomal maintenance 1 (CRM1) rather than adenosine diphosphate (ADP)-ribosylation, acetylation, or oxidation. HMGB1, as well as lysine acetylation and cysteine disulfide oxidation of secreted HMGB1, were monitored by sensitive and specific assays using immunoprecipitation, stable isotope dilution, differential alkylation, and nano liquid chromatography parallel reaction monitoring/high-resolution mass spectrometry (nano-LC-PRM/HRMS). A major fraction of the HMGB1 secreted by low-dose cisplatin treatment of A549 NSCLC cells was found to be in the fully reduced form. In contrast, mainly oxidized forms of HMGB1 were secreted by dimethyl sulfoxide (DMSO)-mediated apoptosis. These findings suggest that inhibition of XPO1 could potentiate the anti-tumor activity of cisplatin by increasing the nuclear accumulation of HMGB1 protein, an inhibitor of cisplatin DNA-adduct repair. Furthermore, low-dose cisplatin therapy could modulate the immune response in NSCLC through the established chemokine activity of extracellular reduced HMGB1. This could potentially enhance the efficacy of subsequent immunotherapy treatment.

Current therapies for treating Glioblastoma (GB), and brain tumours in general, are inefficient and represent numerous challenges. In addition to surgical resection, chemotherapy and radiotherapy are presently used as standards of care. However, treated patients still face a dismal prognosis with a median survival below 15-18 months. Temozolomide (TMZ) is the main chemotherapeutic agent administered; however, intrinsic or acquired resistance to TMZ contributes to the limited efficacy of this drug. To circumvent the current drawbacks in GB treatment, a large number of classical and non-classical platinum complexes have been prepared and tested for anticancer activity, especially platinum (IV)-based prodrugs. Platinum complexes, used as alkylating agents in the anticancer chemotherapy of some malignancies, are though often associated with severe systemic toxicity (i.e., neurotoxicity), especially after long-term treatments. The objective of the current developments is to produce novel nanoformulations with improved lipophilicity and passive diffusion, promoting intracellular accumulation, while reducing toxicity and optimizing the concomitant treatment of chemo-/radiotherapy. Moreover, the blood-brain barrier (BBB) prevents the access of the drugs to the brain and accumulation in tumour cells, so it represents a key challenge for GB management. The development of novel nanomedicines with the ability to (i) encapsulate Pt-based drugs and pro-drugs, (ii) cross the BBB, and (iii) specifically target cancer cells represents a promising approach to increase the therapeutic effect of the anticancer drugs and reduce undesired side effects. In this review, a critical discussion is presented concerning different families of nanoparticles able to encapsulate platinum anticancer drugs and their application for GB treatment, emphasizing their potential for increasing the effectiveness of platinum-based drugs.

BACKGROUND: In cancer chemotherapy platinum drugs do cause damage to the normal cells and as a result, many physiological functions are derailed. Renal function as measured by measured glomerular filtration rate (mGFR) plays a large role in drug dosing on the basis of the maximum tolerated dose, which is the highest dose that may be administered without unacceptable toxicity, to maximize anticancer efficacy.
OBJECTIVE: The objective of the study was to compare the toxic effect of platinum drugs on renal function as measured by mGFR in patients with malignancy and to study the difference in the magnitude of nephrotoxicity by these drugs.
METHODS: The study was conducted in the Department of Physiology in close collaboration with the Department of Radiotherapy at a tertiary care centre in Western Rajasthan, India. 150 patients suffering from different malignances undergoing treatment with cisplatin, carboplatin, and oxaliplatin were examined for their renal function as measured by mGFR using 99mTc-diethylene triamine pentaacetic acid (99mTc-DTPA) and were compared with 50 subjects of control group.
RESULTS:  In the cisplatin group there was a gradual fall of GFR from 85.49 ml/min/1.73sqm to 58.09ml/min/1.73sqm at cycle II. In the carboplatin group it was 84.86ml/min/1.73sqm at baseline whereas cycle II was 75.5 ml/min/1.73sqm with SD ± 16.49. mGFR fell significantly (p<0.0001) in cisplatin and carboplatin groups but not in the cohort of patients who received oxaliplatin. The GFR reduction continued from the baseline to cycle I and then cycle II in cisplatin and carboplatin groups.
CONCLUSIONS: Nephrotoxicity is a major side effect of platin drugs and further studies should be done to establish their optimal dose in relation to renal function and minimize toxicity by trying various cytoprotective agents.

Platinum-based drugs are the first line of therapeutics against many cancers, including lung cancer. Lung cancer is one of the leading causes of cancer-related death worldwide. Platinum-based agents target DNA and prevent replication, and transcription, leading to the inhibition of cell proliferation followed by cellular apoptosis. About twenty-three platinum-based drugs are under different stages of clinical trials, among cisplatin, carboplatin, and oxaliplatin are widely used for the treatment of various cancers. Among them, cisplatin is the most commonly used drug for cancer therapy, which binds with RNA, and hinders the cellular RNA process. However, long-term use of platinum-based drugs can cause different side effects and has been shown to develop chemoresistance, leading to poor clinical outcomes. Chemoresistance became an important challenge for cancer treatment. Platinum-based chemoresistance occurs due to the influence of intrinsic factors such as overexpression of multidrug resistance proteins, advancement of DNA repair mechanism, degradation, and deactivation of intracellular thiols. Recently, epigenetic modifications, especially non-coding RNAs (ncRNAs) mediated gene regulation, grasp the attention for reversing the sensitivity of platinum-based drugs due to their reversible nature without altering genome sequence. ncRNAs can also modulate the intrinsic and non-intrinsic mechanisms of resistance in lung cancer cells. Therefore, targeting ncRNAs could be an effective approach for developing novel therapeutics to overcome lung cancer chemoresistance. The current review article has discussed the role of ncRNA in chemoresistance and its underlying molecular mechanisms in human lung cancer.

Colorectal cancer (CRC) can be resistant to platinum drugs, possibly through ferroptosis suppression, albeit the need for further work to completely understand this mechanism. This work aimed to sum up current findings pertaining to oxaliplatin resistance (OR) or resistance to ascertain the potential of ferroptosis to regulate oxaliplatin effects. In this review, tumor development relating to iron homeostasis, which includes levels of iron that ascertain cells\' sensitivity to ferroptosis, oxidative stress, or lipid peroxidation in colorectal tumor cells that are connected with ferroptosis initiation, especially the role of c-Myc/NRF2 signaling in regulating iron homeostasis, coupled with NRF2/GPX4-mediated ferroptosis are discussed. Importantly, ferroptosis plays a key role in OR and ferroptotic induction may substantially reverse OR in CRC cells, which in turn could inhibit the imbalance of intracellular redox induced by oxaliplatin and ferroptosis, as well as cause chemotherapeutic resistance in CRC. Furthermore, fundamental research of small molecules, ferroptosis inducers, GPX4 inhibitors, or natural products for OR coupled with their clinical applications in CRC have also been summarized. Also, potential molecular targets and mechanisms of small molecules or drugs are discussed as well. Suggestively, OR of CRC cells could significantly be reversed by ferroptosis induction, wherein this result is discussed in the current review. Prospectively, the existing literature discussed in this review will provide a solid foundation for scientists to research the potential use of combined anticancer drugs which can overcome OR via targeting various mechanisms of ferroptosis. Especially, promising therapeutic strategies, challenges ,and opportunities for CRC therapy will be discussed.

UNASSIGNED: With the widespread application of platinum drugs in antitumor therapy, the incidence of platinum drug adverse events (ADEs) is always severe. This study aimed to explore the adverse event signals of Cisplatin, Carboplatin and Oxaliplatin, three widely used platinum-containing drugs, and to provide a reference for rational individualized clinical drug use.
UNASSIGNED: The adverse event report data of the three platinum drugs from the first quarter of 2017 to the fourth quarter of 2021 were extracted from the FAERS database, and the data mining and risk factors for the relevant reports were carried out using the reporting odds ratio (ROR) method the proportional reporting ratio (PRR)and the comprehensive criteria (MHRA) method.
UNASSIGNED: A total of 1853 effective adverse event signals were obtained for the three platinum agents, including 558 effective signals for Cisplatin, 896 effective signals for Carboplatin, and 399 effective signals for Oxaliplatin. The signals involve 23 effective different system organs (SOCs). The adverse events of Cisplatin are mainly fixed on blood and lymphatic system diseases, gastrointestinal diseases, systemic diseases and various reactions at the administration site. The adverse events of Carboplatin are mainly focused on blood and lymphatic system diseases, respiratory system, thoracic and mediastinal diseases, while the adverse events of Oxaliplatin are mainly concentrated in respiratory system, thoracic and mediastinal diseases, various nervous system diseases, and gastrointestinal system diseases.
UNASSIGNED: It was found that the main systems involved in common adverse events of platinum drugs are different, and the correlation strength of platinum drugs with the certain adverse events of each system is different.

Gliomas are the most common and malignant primary tumors of the central nervous system (CNS). Glioblastomas are the most malignant and aggressive form of primary brain tumors and account for the majority of brain tumor-related deaths. The current standard treatment for gliomas is surgical resection supplemented by postoperative chemotherapy. Platinum drugs are a class of chemotherapeutic drugs that affect the cell cycle, and the main site of action is the DNA of cells, which are common chemotherapeutic drugs in clinical practice. Chemotherapy with platinum drugs such as cisplatin, carboplatin, oxaliplatin, or a combination thereof is used to treat a variety of tumors. However, the results of gliomas chemotherapy are unsatisfactory, and resistance to platinum drugs is one of the important reasons. The resistance of gliomas to platinum drugs is the result of a combination of influencing factors. Decreased intracellular drug concentration, enhanced function of cell processing active products, enhanced repair ability of cellular DNA damage, and blockage of related apoptosis pathways play an important role in it. It is known that the pathogenic properties of glioma cells and the response of glioma towards platinum-based drugs are strongly influenced by non-coding RNAs, particularly, by microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs and lncRNAs control drug sensitivity and the development of tumor resistance towards platinum drugs. This mini-review summarizes the resistance mechanisms of gliomas to platinum drugs, as well as molecules and therapies that can improve the sensitivity of gliomas to platinum drugs.