Platinum Salts Research Articles

An Experimental Biological Test to Diagnose Hypersensitivity Reactions to Carboplatin: New Horizons for an Old Problem

Carboplatin, a second-generation platinum compound, is a chemotherapeutic drug effective in many types of cancers. Its use is limited by the development of systemic allergic reactions in up to 30% of the cancer patients. Therefore, it is very important to make a correct diagnosis of true carboplatin allergy, for the crucial clinical implications. In this regard, no biological test is actually available to detect specific immunoglobulin E in the sera of patients allergic to carboplatin. We evaluated a new experimental biological test in patients with suspected immunoglobulin E-mediated reactions to carboplatin. Three patients with suspected hypersensitivity reactions to carboplatin underwent skin tests with an undiluted aliquot (10 mg/ml) of carboplatin preparation planned for infusion. Total serum immunoglobulin E and specific immunoglobulin E to the two platinum salts carboplatin and cisplatin were determined with the ImmunoCAP system (Phadia AB, Uppsala, Sweden). We detected specific immunoglobulin E to carboplatin in all three patients, whereas specific immunoglobulin E to cisplatin was observed in one patient. The positivity of specific immunoglobulin E against carboplatin in these three patients is a new and encouraging observation for the development of a new important instrument that can help clinicians in their therapeutic decisions, after a hypersensitivity reaction to a platinum salt.

Enamides and Related Functional Groups as Nucleophilic Components in Ring-Forming Processes Catalyzed by Electrophilic Metal Salts

This Account describes the development of reactions catalyzed by platinum(II), silver(I), or gold(I) salts using substrates that feature enamides, enecarbamates, or enesulfonamides as nucleophilic functional groups.

Systemic chemotherapy in patients with advanced transitional cell carcinoma of the urothelium and impaired renal function

Cisplatin is the backbone of chemotherapeutic regimens used in the treatment of advanced transitional cell carcinoma of the urothelium. However, about 50% of patients cannot be administered cisplatin because of impaired renal functions. A review of the different approaches that have been developed in this patient population was performed through a Medline search from 1 January 1998 to 31 December 2010. Twenty-six studies including 25 phase II and one randomized phase II/III studies were analyzed. All regimens, except one, were based on gemcitabine and/or carboplatin and/or paclitaxel. Only five (20%) out of 25 phase II studies actually include homogeneous patients with an impaired renal function defined by a creatinine clearance below 60 ml/min. One hundred and eight patients with a median creatinine clearance ranging from 28 to 48 ml/min received four different chemotherapy regimens including one to four drugs. The results showed the response rates to vary from 24 to 56% and survival to range from 7 to 15 months. No standard chemotherapy can be recommended from literature data. Future randomized studies will have to solve the following questions: what is the optimal definition of cisplatin eligibility? Which platinum salt should be used? Is a platinum salt necessary? How many drugs should be delivered?

Effects of Carbon–Metal–Carbon Linkages on the Optical, Photophysical, and Electrochemical Properties of Phosphametallacycle-Linked Coplanar Porphyrin Dimers

5-(Diphenylphosphanyl)-10,15,20-triarylporphyrins (meso-phosphanylporphyrins) underwent complexations with palladium(II) and platinum(II) salts to afford phosphapalladacycle- and phosphaplatinacycle-fused coplanar porphyrin dimers, respectively, via regioselective peripheral β-C-H activation of the meso-phosphanylporphyrin ligands. The optical and electrochemical properties of these metal-linked porphyrin dimers as well as their porphyrin monomer/dimer references were investigated by means of steady-state UV-vis absorption/fluorescence spectroscopy, cyclic and differential pulse voltammetry, time-resolved spectroscopy (fluorescence and transient absorption lifetimes and spectra), and magnetic circular dichroism spectroscopy. All the observed data clearly show that the palladium(II) and platinum(II) linkers play crucial roles in the electronic communication between two porphyrin chromophores at the one-electron oxidized state and in the singlet-triplet intersystem-crossing process at the excited state. It has also been revealed that the C-Pt-C linkage makes more significant impacts on these fundamental properties than the C-Pd-C linkage. Furthermore, density functional theory calculations on the metal-linked porphyrin dimers have suggested that the antibonding dπ-pπ orbital interaction between the peripherally attached metal and adjacent pyrrolic β-carbon atoms destabilizes the highest occupied molecular orbitals of the porphyrin π-systems and accounts for the observed unique absorption properties. On the basis of these experimental and theoretical results, it can be concluded that the linear carbon-metal-carbon linkages weakly but definitely perturb the optical, photophysical, and electrochemical properties of the phosphametallacycle-linked coplanar porphyrin dimers.

FOLFIRI regimen in metastatic pancreatic adenocarcinoma resistant to gemcitabine and platinum-salts

To evaluate the efficacy and safety of the FOLFIRI regimen in patients with metastatic pancreatic adenocarcinoma (PAC) after the failure of gemcitabine and platinum salts. All consecutive patients with histologically confirmed, metastatic PAC and World Health Organization performance status (PS) ≤ 2 received FOLFIRI-1 [irinotecan 180 mg/m(2) on day 1 and leucovorin 400 mg/m(2) followed by 5-fluorouracil (5-FU) 400 mg/m(2) bolus, then 5-FU 2400 mg/m(2) as a 46-h infusion, biweekly] or FOLFIRI-3 (irinotecan 100 mg/m(2) on day 1 and leucovorin 400 mg/m(2), then 5-FU 2400 mg/m(2) as a 46-h infusion and irinotecan 100 mg/m(2) repeated on day 3, biweekly) after failure of gemcitabine and platinum-based chemotherapies as a systematic policy in two institutions between January 2005 and May 2010. Tumor response, time to progression (TTP), overall survival rate (OS) and grade 3-4 toxicities were retrospectively studied. Subgroup analyses were performed to search for prognostic factors. Sixty-three patients (52.4% male, median age 59 years) were analyzed. Among them, 42.9% were PS 0, 38.1% were PS 1 and 19.0% were PS 2. Fifty one patients (81.0%) had liver metastases. Before the FOLFIRI regimen, patients had received 1 line (n = 19), 2 lines (n = 39) or 3 lines (n = 5) of chemotherapy. Median TTP obtained with the line before FOLFIRI was 3.9 mo (95% CI: 3.4-5.3 mo). A total of 480 cycles was completed (median: 6 cycles, range: 1-51 cycles). The main reason for discontinuing FOLFIRI was tumor progression (90.3%). Tumor control was achieved in 25 patients (39.7%) (partial response: n = 5, stable disease: n = 20) with FOLFIRI. Median TTP was 3.0 mo (95% CI: 2.1-3.9 mo) and median OS was 6.6 mo (95% CI: 5.3-8.1 mo). Dose adaptation was required in 36 patients (57.1%). Fifteen patients (23.8%) had grade 3-4 toxicities, mainly hematological (n = 11) or digestive (n = 4). Febrile neutropenia occurred in 3 patients. There was no toxic death. PS 2 was significantly associated with poor TTP [hazard ratio (HR): 16.036, P < 0.0001] and OS (HR: 4.003, P = 0.004). The FOLFIRI regimen had an acceptable toxicity and an interesting efficacy in our study, limited to patients in good condition (PS 0-1).

Controlling growth of self-propagating molecular assemblies

A series of six self-propagating molecular assemblies (SPMAs) were generated by alternative solution-deposition of ruthenium polypyridyl complexes and d8palladium and platinum salts on glass and silicon substrates. The d6 polypyridyl complexes have three pyridine units available for forming networks by coordination to the metal salts. This two-step film growth process is fast (15 min/step) and can be carried out conveniently under ambient conditions in air. The reactivity of the common metal salts (ML2X2: M = Pd, X = Cl, L = PhCN, ½ 1,5-cyclooctadiene (COD), SMe2 and M = Pt, X = Cl, Br, I, L = PhCN) is a dominant factor in the film growth. Although the assembly structures are comparable, their exponential growth can be controlled by varying the metals salts. The co-ligands, halides, and metal centers can be used to control the film thicknesses and light absorption intensities of the metal-to-ligand charge transfer (MLCT) bands by a factor of ∼3.5 for 13 deposition steps, whereas the surface morphologies and molecular densities of the SPMAs are similar. The surface-confined assemblies have been characterized using a combination of optical (UV/Vis, ellipsometry) spectroscopy, atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS), and synchrotron X-ray reflectivity (XRR).

A dual-functional Pt/CNT TCO-free counter electrode for dye-sensitized solar cell

A nanohybrid of platinum and carbon nanotubes (Pt/CNT) with dual functions of catalytic activity and conductivity was synthesized. The selection of the poly(oxyethylene)-backboned polyimide dispersant was essential for preparing the dispersion with the de-bundled CNTs and platinum salts in ethanol/water. Subsequent solution casting and annealing at the optimized temperature of 390 °C led to the in situ reduction of platinum salts and the formation of a thin film of Pt/CNT nanohybrids on the glass substrate. The film was used directly as the counter electrode (CE) in a dye-sensitized solar cell (DSSC), which exhibited a short-circuit current density of 16.6 ± 0.2 mA cm−2 and a power conversion efficiency of 6.96 ± 0.09% at 100 mW cm−2 illumination. This performance is comparable with a DSSC with a conventional Pt-CE, and feasible for replacing the conventional transparent conductive oxide (TCO) conductive layer in DSSCs.

Bronchial asthma and COPD due to irritants in the workplace - an evidence-based approach.

BackgroundRespiratory irritants represent a major cause of occupational obstructive airway diseases. We provide an overview of the evidence related to irritative agents causing occupational asthma or occupational COPD.MethodsWe searched MEDLINE via PubMed. Reference lists of relevant reviews were also screened. The SIGN grading system was used to rate the quality of each study. The modified RCGP three-star system was used to grade the body of evidence for each irritant agent regarding its causative role in either occupational asthma or occupational COPD.ResultsA total of 474 relevant papers were identified, covering 188 individual agents, professions or work-sites. The focus of most of the studies and the predominant diagnosis was occupational asthma, whereas occupational COPD arose only incidentally.The highest level assigned using the SIGN grading was 2+ (well-conducted systematic review, cohort or case–control study with a low risk of confounding or bias). According to the modified RCGP three-star grading, the strongest evidence of association with an individual agent, profession or work-site (“**”) was found for 17 agents or work-sites, including benzene-1,2,4-tricarboxylicacid-1,2-anhydride, chlorine, platinum salt, isocyanates, cement dust, grain dust, animal farming, environmental tobacco smoke, welding fumes or construction work. Phthalic anhydride, glutaraldehyde, sulphur dioxide, cotton dust, cleaning agents, potrooms, farming (various), foundries were found to be moderately associated with occupational asthma or occupational COPD (“*[+]”).ConclusionThis study let us assume that irritant-induced occupational asthma and especially occupational COPD are considerably underreported. Defining the evidence of the many additional occupational irritants for causing airway disorders will be the subject of continued studies with implications for diagnostics and preventive measures.

Stabilisation of water-soluble platinum nanoparticles by phosphonic acid derivatives

Sodium 2-(diphenylphosphino)ethyl phosphonate (1) was investigated as a stabilising agent for platinum nanoparticles (Pt-NPs) in aqueous solution. This phosphino phosphonate is known to stabilise rhodium nanoparticles (NPs) in water. Here we report that in the case of Pt-NPs this ligand is indirectly involved in the stabilisation mechanism and the actual stabilisation agent is the platinum complex Na(2)[Pt(1)(2)] (2). The reduction of platinum(II) salts in the presence of the phosphonates 1, 2, sodium 2-(diphenylphosphoryl)ethyl phosphonate (3) and 3,3,3-triphenylpropyl phosphonate (4) leads to stable platinum NPs with a remarkably narrow particle size distribution. These platinum NPs show high catalytic activity in the hydrogenation of 1-hexene and 1-chloro-3-nitrobenzene under biphasic as well as heterogeneous (supported on charcoal) conditions. The activity of the supported NPs was 30 times higher than the commercially available catalyst Pt(0) EnCat®. Furthermore, the single-crystal X-ray structures of (1)(MeOH)(2)(H(2)O)(2), (3)(H(2)O)(4), and (4)(2)(H(2)O)(17) have been determined.

Synthesis, antiproliferative activity and estrogen receptor α affinity of novel estradiol-linked platinum(II) complex analogs to carboplatin and oxaliplatin. Potential vector complexes to target estrogen-dependent tissues

In the course of efforts to develop 17β-estradiol-linked to anticancer agents targeting estrogen-dependent tissue, we identified three estradiol-linked platinum(II) complex analogs to cisplatin (E-CDDP) derivatives namely: VP-128 ( 1), CD-38 ( 2) and JMP-39 ( 3) that exhibit potent in vitro and in vivo (for derivative VP-128) activity along with interaction with the estrogen receptor α (ERα). In this study, we prepared and biologically evaluated two novel classes of estradiol-linked platinum(II) complex analogs to carboplatin (E-CarboP, 1a– 3a) and oxaliplatin (E-OxaP, 1b– 3b). E-CarboP and E-OxaP were designed and based on the estradiol-linker scaffold of E-CDDP derivatives previously identified. Consequently, we assessed the importance of the nature of platinum(II) salt on the antiproliferative activity on MCF-7 and MDA-MB-231 human mammary carcinoma cell lines together with affinity for the ERα by replacing the dichloroplatinum(II) moiety by a cyclobutane-1,1-dicarboxylateplatinum(II) or an oxalateplatinum(II) moiety. Except for compound 3b which is inactive at the concentration tested, the antiproliferative activity of all compounds on both human mammary carcinomas cell lines are in micromolar range and are more active than carboplatin and oxaliplatin alone but less active that their E-CDDP counterparts ( 1– 3). In addition, E-CarboP derivatives 1a– 3a show very low affinity for ERα whereas E-OxaPs 1b and 2b show higher affinity for ERα than their parents E-CDDPs ( 1– 2), suggesting that the nature of the platinum(II) salt involved in the vector complexes is extremely important to both retain significant antiproliferative activity and selectivity for the ERα and possibility to target estrogen-dependent tissues. Finally, E-OxaPs 1b and 2b are potentially promising alternatives vector complexes to target estrogen-dependent tissues.

ChemInform Abstract: Strategies for the Fabrication of Porous Platinum Electrodes

AbstractReview: 322 refs.

Platinated ultrathin films made of carbon nanotubes

In this study a promising approach for a novel fuel cell catalyst layer is shown using films of carbon nanotubes (CNTs) formed by the layer-by-layer (LbL) method. A special focus is on the dispensing procedure of CNTs in water what is one of the most essential steps to realize monolayers in a reproducible way as targeted in LbL. Furthermore, the platination of the tubes is demonstrated using the reduction of platinum salt in ethylene glycol resulting in a sufficient distribution of nanosized particles. Finally, ultrathin films based on the functionalized nanotubes are investigated with atomic force microscopy, showing promising results for the future use as catalyst layer.

Analgésie péridurale pour le traitement chirurgical des carcinoses péritonéales : une pratique à risque ?

Background To study the risks of haemodynamic instability, and the possible occurrence of spinal haematoma, meningitis and epidural abscess when epidural analgesia is performed for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Methods We retrospectively analyzed the data of 35 patients treated by HIPEC with oxaliplatin or cisplatin. An epidural catheter was inserted before induction of general anaesthesia. Postoperatively, a continuous epidural infusion of ropivacain, then a patient-controlled epidural analgesia were started. Results The epidural catheter was used peroperatively before HIPEC in 12 subjects (34%), and after HIPEC in 23 subjects (66%). The median dose of ropivacain given peroperatively in the epidural catheter was 40 mg (30–75). Norepinephrin was used in two subjects (6%) peroperatively (median infusion rate 0.325 μg/kg per minute [0.32–0.33]), and in four subjects (11%) in the postoperative 24 hours. No spinal haematoma, meningitis or epidural abscess were noted. Five subjects (14%) had a thrombopenia or a prothrombin time less than 60% before catheter removal. Two subjects (6%) had a leukopenia before catheter removal. No thrombopenia or blood coagulation disorders were recorded the day of catheter removal. Conclusion In this series of 35 patients, the use of epidural analgesia for HIPEC does not seem to be associated with a worse risk of haemodynamic instability, spinal haematoma, meningitis or epidural abscess. HIPEC with platinum salt is not incompatible with the safety of epidural analgesia, with an optimized fluid management peroperatively and the following of perimedullary anesthesia practice guidelines.

New strategy to prepare platinum salts by electrochemical methods and subsequent synthesis of platinum nanoparticles

As shown in the literature, most of Pt nanoparticles (NPs) were synthesized from precursors of commercial Pt salts. However, the impurity of the commercial Pt salts is a concerned issue. In this work, we report a new pathway based on electrochemical methods to prepare Pt-containing complexes with high purity in aqueous solutions from bulk Pt substrates. Experimental results indicate that Pt complexes with higher concentration can be obtained in 0.1 N HCl by using square-wave oxidation–reduction cycles (ORCs) under a frequency of 8 Hz with a step potential of 6.3 mV. Moreover, concentrations of other heavy metals of Hg and Cr in 65 ppm Pt complexes-containing solution are just 0.65 and 0.78 ppb, respectively. These Pt complexes were further reduced to Pt NPs by using NaBH 4 and poly(vinylpyrrolidone) (PVP) as reducing agent and stabilizer, respectively. The concentration and the particle size of synthesized Pt (1 1 1) NPs are ca. 60 ppm and smaller than 5 nm, respectively.

Abstract B54: Phase I study of ombrabulin in combination with cisplatin (CDDP) administered every 3 weeks to Japanese patients with advanced solid tumors.

Abstract Background: Ombrabulin, an analog of Combretastatin A4, is a vascular disrupting agent that destroys established tumor vasculature, causing blood perfusion shutdown and tumor necrosis. However, a narrow rim of tumor cells remains at the tumor periphery after single agent ombrabulin therapy that necessitates its combination with other anticancer therapy (ies). Ombrabulin in combination with platinum derivatives has shown synergistic activity in animal models. Dramatic decrease of tumor blood perfusion was shown by DCE-US in a clinical study when ombrabulin was given in combination with CDDP to patients (pts) with solid tumors. In Caucasian pts, the recommended dose (RD) was established at 25 mg/m2 for ombrabulin and 75 mg/m2 for CDDP, given every 3 weeks. Phase II studies in combination with taxanes and platinum salts in lung and ovarian cancers, and a Phase III study with cisplatin in advanced soft tissue sarcoma are ongoing. Objectives: The primary objective of the study was to determine the recommended dose (RD) and the dose-limiting toxicities (DLTs) of ombrabulin in combination with cisplatin in Japanese pts with advanced solid tumors. Secondary objectives were the assessment of the overall safety profile, the pharmacokinetic (PK) profile and preliminary anti-tumor activity (RECIST). Methods: This was an open-label, sequential-cohort, dose-escalation study of intravenous ombrabulin administered immediately followed by a CDDP infusion every 3 weeks (ClinicalTrials.gov: NCT01021150). Cohorts of 3 or 6 pts were treated at 15.5 and 25 mg/m2 of ombrabulin in combination with 75 mg/m2 of CDDP (fixed dose). DLTs were to be evaluated during the first treatment cycle. RD was defined as the highest ombrabulin dose at which less than 33% of all evaluable pts experienced DLTs. PK of ombrabulin, its metabolite RPR258063 and total/ultrafilterable CDDP were measured at Cycle 1 on Day 1, 2, 3. Results: Ten pts (4 at 15.5 mg/m2 and 6 at 25 mg/m2) were treated (M/F, 5/5; median age, 49.5 [31–67]; and ECOG PS 0/1, 8/2). The most frequent tumor types were breast (3 pts) and esophagus (2 pts). The median number of cycles was 4.0 (range 1–6). Neither DLT nor serious cardiovascular adverse events (AE) were observed. The RD was defined at ombrabulin 25 mg/m2 and CDDP at 75 mg/m2. No grade 3/4 AE were observed at RD other than neutropenia, which occurred in 3/6 pts. The most frequent treatment-related AEs observed at RD were neutropenia (83.3%), decreased appetite (83.3%), hiccups (83.3%), constipation (83.3%), nausea (83.3%) and fatigue (83.3%). One patient (carcinoma of unknown primary) had a partial response and 5 pts had a stable disease as per RECIST. Preliminary PK parameters of ombrabulin, RPR258063 and total/ultrafilterable CDDP were in the range of those observed in non-Japanese pts. Conclusions: In this study, ombrabulin in combination with CDDP was well tolerated in line with results of prior studies. Based on the results from this study, the RD for Japanese pts was defined as 25 mg/m2 of ombrabulin and 75 mg/m2 of CDDP, identical to the one in Caucasian pts. Antitumor activity was observed in different tumor types and at different ombrabulin doses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2011 Nov 12-16; San Francisco, CA. Philadelphia (PA): AACR; Mol Cancer Ther 2011;10(11 Suppl):Abstract nr B54.

Fabrication and performance of catalyst-coated membranes by layer-by-layer deposition of catalyst onto Nafion for polymer electrolyte membrane fuel cells

In this contribution, four comparative methods are described for the preparation of catalyst coated membranes (CCMs) via using layer-by-layer (LbL) technique. In the first method, LbL composite membrane is immersed into H 2PtCl 6 solution followed by reduction to metallic Pt. Secondly, Pt–C (Hispec 3000) dispersed in the positively charged polyelectrolyte is assembled onto the membrane support. Thirdly, anionic polyelectrolyte with external salt is used for the preparation of CCM. In the fourth method, reductive precipitation of platinum salt loaded on Vulcan XC complexes within LbL multilayer in the presence of Nafion solution takes place. From SEM analysis, it is observed that the polyelectrolytes are deposited onto both sides of the pre-treated Nafion ®117 membrane successfully with Pt loadings of 0.023 μg cm −2 and 0.15 μg cm −2 for CCMs prepared according to method 1 reduced in 10 and 30 min, respectively. Single cell performance of MEA-6 based on CCM (PAH/PSS–H 2PtCl 6–Vulcan XC72–Nafion) prepared according to method 4 displays the best output performance (98 mW cm −2) due to the improved contact between the catalyst layer and the membrane. Furthermore the cell performance of MEA-6 is significantly improved (18%) due to creating new path for fuel and catalyst interaction (three phase boundary) compared to pristine Nafion ®117 based MEA.

Preparation and Characterization of Platinum/Polyaniline Core-Shell Composite

Abstract. The core-shell composite of platinum/polyaniline (Pt@PAN) had been prepared by chemical synthesis approach. Reduction of the platinum salt in aqueous solution leaded to the formation of platinum nanoparticles, and then polyaniline were synthesized by interfacial polymerization to get Pt@PAN composite. Transmission electron microscopy of Pt@PAN showed Pt particles are uniform with spherical and granular morphology. Pt@PAN was also characterized by EDAX, XPS and FTIR.

Strategies for the Fabrication of Porous Platinum Electrodes

Porous platinum is of high technological importance due to its various applications in fuel cells, sensors, stimulation electrodes, mechanical actuators and catalysis in general. Based on a discussion of the general principles behind the reduction of platinum salts and corresponding deposition processes this article discusses techniques available for platinum electrode fabrication. The numerous, different strategies available to fabricate platinum electrodes are reviewed and discussed in the context of their tuning parameters, strengths and weaknesses. These strategies comprise bottom-up approaches as well as top-down approaches. In bottom-up approaches nanoparticles are synthesized in a fi rst step by chemical, photochemical or sonochemical means followed by an electrode formation step by e.g. thin fi lm technology or network formation to create a contiguous and conducting solid electrode structure. In top-down approaches fabrication starts with an already conductive electrode substrate. Corresponding strategies enable the fabrication of substrate-based electrodes by e.g. electrodeposition or the fabrication of self-supporting electrodes by dealloying. As a further top-down strategy, this review describes methods to decorate porous metals other than platinum with a surface layer of platinum. This way, fabrication methods not performable with platinum can be applied to the fabrication of platinum electrodes with the special benefit of low platinum consumption.

Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers.

Breast and ovarian cancer are among the most common malignancies diagnosed in women worldwide. Together, they account for the majority of cancer-related deaths in women. These cancer types share a number of features, including their association with hereditary cancer syndromes caused by heterozygous germline mutations in BRCA1 or BRCA2. BRCA-associated breast and ovarian cancers are hallmarked by genomic instability and high sensitivity to DNA double-strand break (DSB) inducing agents due to loss of error-free DSB repair via homologous recombination (HR). Recently, poly(ADP-ribose) polymerase inhibitors, a new class of drugs that selectively target HR-deficient tumor cells, have been shown to be highly active in BRCA-associated breast and ovarian cancers. This finding has renewed interest in hallmarks of HR deficiency and the use of other DSB-inducing agents, such as platinum salts or bifunctional alkylators, in breast and ovarian cancer patients. In this review we discuss the similarities between breast and ovarian cancer, the hallmarks of genomic instability in BRCA-mutated and BRCA-like breast and ovarian cancers, and the efforts to search for predictive markers of HR deficiency in order to individualize therapy in breast and ovarian cancer.

Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Cancers of unknown primary site: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up