Cis- diamminedichloroplatinum (cisplatin) is one of the most commonly used present day hemotherapeutic agents. It is used to treat a wide range of cancers including head and neck, lung, gastrointestinal tract, ovarian and genitourinary cancers. However, dose- limiting toxicity is often associated with cisplatin. It is known that cisplatin works more effectively with dose escalation, but significant risk for nephrotoxicity is often associated with higher doses [1]. Recovery of renal function occurs over a period of 2-4 weeks, although lack of recovery can also take place [2]. Kidney accumulates cisplatin in much higher concentration in comparison to other organs and is the major route of its excretion [3]. Five times higher cisplatin concentration was observed in proximal tubular epithelial cells in comparison to serum [4]. Highest accumulation of cisplatin occurs in S3 segment of proximal tubule followed by the distal collecting tubule and the S1 segment of proximal tubule [5]. Cisplatin nephrotoxicity may be presented in various ways of which the most serious presentation is acute kidney injury, which occurs in 20-30% of patients despite hyperhydration and forced Diuresis [6].

Non-Hodgkin’s lymphomas (NHLs) are the second fastest growing cancer in terms of incidence and deaths in the United States and Europe. NHLs are a heterogeneous cancer group including several haematological neoplasias with different degree of aggressiveness. In spite of the progresses, conventional therapies do not ensure long-term survival [1]. The NHL patients, who have a poor life expectation, could take advantage from innovative therapeutic strategies, such as immunotherapy. Specific antibodies can preferentially bind tumour cells over normal tissues. This specificity is based upon characteristics (surface antigens) that are completely independent from the parameters that allow for differential toxicity of chemo- and radiotherapy. The vascular nature of most lymphomas and their antigen expression make these tumours a favourable setting for treatment with monoclonal antibodies. In fact, the first successful use of antibodies as treatments for cancer was demonstrated in NHLs [2,3]. CD20 has been largely exploited as target antigen for immunotherapy with antibodies because it is expressed at high levels on B-lymphoma cells and is not expressed on stem cells [4].

Thyroid cancer (TC) is the most common endocrine malignancy and its incidence hasbeen increasing sharply since the mid-1990s [1]. TC is a general term that comprises two main groups of neoplasias, depending on the cell type affected by the malignant transformation. 1) Carcinomas originating from the follicular epithelium, referred to as nonmedullary thyroid cancer (NMTC) representing more than 95% of all TC; and 2) carcinomas originating from the parafollicular thyroid C cells, referred to as medullary thyroid cancer (MTC) accounting less than 5% of all TC.

Eribulin sensitivity was examined in a panel of twenty-five human cancer cell lines representing a variety of tumor types, with a preponderance of breast and lung cancer cell lines. As expected, the cell lines vary in sensitivity to eribulin at clinically relevant concentrations. To identify combination drugs capable of increasing anticancer effects in patients already responsive to eribulin, as well as inducing de novo anticancer effects in non-responders, we performed a combinatorial high throughput screen to identify drugs that combine with eribulin to selectively kill tumor cells. Among other observations, we found that inhibitors of ErbB1/ErbB2 (lapatinib, BIBW-2992, erlotinib), MEK (E6201, trametinib), PI3K (BKM-120), mTOR (AZD 8055, everolimus), PI3K/mTOR (BEZ 235), and a BCL2 family antagonist (ABT-263) show combinatorial activity with eribulin. In addition, antagonistic pairings with other agents, such as a topoisomerase I inhibitor (topotecan hydrochloride), an HSP-90 inhibitor (17-DMAG), and gemcitabine and cytarabine, were identified. In summary, the preclinical studies described here have identified several combination drugs that have the potential to either augment or antagonize eribulin’s anticancer activity. Further elucidation of the mechanisms responsible for such interactions may be important for identifying valuable therapeutic partners for eribulin.

The financial crisis has a dramatic impact on social life, since reduced or even non-existent incomes affect people’s well-being and push big parts of the population to poverty. The individuals’ financial status affects health indicators such as life expectancy, morbidity, mortality and healthcare service accessibility [1].