The interindividual variability in pharmacokinetics represents one of the factors involved in difference of both efficacy and toxicity of anticancer drugs prescribed to patients with the same cancer disease. The causes of pharmacokinetic interindividual variability are themselves divers. The impaired organic function corresponding either to liver or kidneys represents the major cause since any impaired function is systematically responsible of pharmacokinetic modifications, and due to the amplitude of these modifications. In this article, the clinically relevant pharmacokinetic parameters are shown. The methodologies used to study the pharmacokinetic variability due to impaired organic functions and to control them are detailed.

Platinum compounds represent a pharmacological class, essential for the treatment of some cancer diseases. The three molecules, cisplatin, carboplatin, and oxaliplatin, share some physiochemical and pharmacological properties, in particular the ability to form DNA adducts. However, oxaliplatin presents some mechanisms of resistance different to those of cisplatin and carboplatin. Carboplatin may be considered as an analogue of cisplatin, but its pharmacokinetic properties, side effects, and intrinsic activity are significantly different from those of cisplatin, then the choice of one of these two compounds may be done rationally in function of the patients' characteristics. The cellular mechanisms involved in these differences are described in this general review.

Microtubules are dynamic filamentous cytoskeletal proteins that are an important therapeutic target in patients with tumors. Microtubule binding agents have been part of the pharmacopoeia of cancer for decades, and until the advent of targeted therapy microtubules represented the only alternative to DNA as a therapeutic target in cancer. There are currently a variety of available vinca alkaloids and taxanes and other agents, such as ixabepilone and eribulin, have also been approved. Maytansinoids have been used for the production of immunoconjugates, monoclonal antibodies covalently bound to antimitotic molecules. The screening of a variety of botanical species and marine organisms continues to yield promising new antitubulin agents with novel properties. Enhanced tumor specificity, reduced neurotoxicity, and insensitivity to chemoresistance mechanisms are the three main objectives in the current search for novel microtubule binding agents.

With the approval of mechlorethamine by the FDA in 1949 for the treatment of hematologic malignancies, alkylating agents are the oldest class of anticancer agents. Even though their clinical use is far beyond the use of new targeted therapies, they still occupy a major place in specific indications and sometimes represent the unique option for the treatment of refractory diseases. Here, we are reviewing the major classes of alkylating agents and their mechanism of action, with a particular emphasis for the new generations of alkylating agents. As for most of the chemotherapeutic agents used in the clinic, these compounds are derived from natural sources. With a complex but original mechanism of action, they represent new interesting alternatives for the clinicians, especially for tumors that are resistant to conventional DNA damaging agents. We also briefly describe the different strategies that have been or are currently developed to potentiate the use of classical alkylating agents, especially the inhibition of pathways that are involved in the repair of DNA lesions induced by these agents. In this line, the development of PARP inhibitors is a striking example of the recent regain of interest towards the "old" alkylating agents.

Cell cycle progression corresponds to a series of events, which succeed one another to end in the division of a mother cell to give two daughter cells. The processes that allow the cell to divide are very precisely controlled by a multitude of enzymatic reactions among which protein phosphorylation, carried out by protein kinases, plays a key role. Serine/threonine kinases are enzymes that catalyse the transfer of a phosphate from ATP to a protein substrate, more precisely on a serine or threonine amino acid residue. Three important families of serine/threonine kinases are involved in the regulation of cell cycle progression, the cyclin dependent kinase (CDK) the polo-like kinase (PLK) and those of the Aurora family. The cancer is described as an uncontrolled cell division process. Cancer cells proliferate indeed in an anarchic way, and carry out cycles of cellular division by being unaware of the signals of alarm. A simple idea thus appeared soon: to stop or to slow down cell cycle progression would result in inhibiting cell proliferation and thus fighting against cancer. Cell cycle progression being controlled in particular by protein kinases of the CDK, PLK and Aurora families, it was rapidly decided to look for inhibitors of those protein kinases. We will first make a general recall on cell cycle progression and the mechanisms that control it. The functions of protein kinases of the CDK, PLK and Aurora families will then be described by concentrating on the sensitive phase of the cell cycle progression, i.e. mitosis. Finally, we will approach the consequences of the inhibition of these protein kinases within the framework of the fight against cancer.

The nuclear estrogen receptors (ER) are the major targets for endocrine treatment of hormone-dependent breast cancers. Hormone therapy blocked endogenous estrogen activation of ER, either by competitive inhibition of endogenous estrogens (selective estrogen receptor modulators - SERM or selective estrogen receptor down regulators - SERD) or by inhibition of estrogen synthesis (aromatase inhibitors) from adrenal androgens in post-menopausal women. The efficacy of these treatments has been shown on large series of breast cancer patients. However de novo or acquired resistance to treatment occurs. The better knowledge of the mechanism of action of such treatment may help to better understand them, and also for the determinism of adverse side effects of the different class of molecules.

While new anticancer angiogenesis inhibitors present a well-tolerated safety profile, they are not without adverse events. The signaling pathways and/or receptors inhibited by these new drugs are often physiologically expressed in the skin and/or hair follicle and cutaneous toxicity is on the forefront. This article reviews the main dermatologic adverse events induced by these targeted anticancer therapies with a partial or exclusive antiangiogenic activity: sorafenib, sunitinib, pazopanib, vandetanib, everolimus, temsirolimus or bevacizumab.

Octreotide is a synthetic octapeptide having properties related to those of natural somatostatin, a hypothalamic hormone. We report a case of eruptive naevus in patients treated with octreotide.

Angiogenesis inhibitor drugs, targeting VEGF (vascular endothelial growth factor) are used increasingly in oncology for a wide range of advanced cancers (colorectal cancer, lung cancer, renal cell cancer,...). Generally, they are well tolerated but cardiovascular and renal side effects may appear. The most frequent complications are hypertension and proteinuria which, very often, remain asymptomatic. Therefore, they have to be searched for systematically before and during the treatment. Sometimes, anti-hypertensive medication is needed. We are just beginning to understand the pathophysiological mechanisms of antiangiogenic therapies. Only a multidisciplinary approach will improve our knowledge of those target agents and allow a better management of the cancer patient.

Soft tissue sarcomas account for 1% of all malignant tumours. Until a few years ago, doxorubicine and ifosfamide were the only active chemotherapy drugs in the metastatic setting. Recently, a new drug has proven its efficacy after failure of standard treatments: the trabectedin; its activity is based on interference with ADN repair mechanisms. Trabectedin has just been also validated and reimbursed in patients with ovarian cancer, in partially sensitive recurrence. In this paper, we will review the mechanism of action and the clinical results of trabectedin.

The main objectives of this literature review are to determine if scalp cooling is efficient and safe, if there are side effects and if the patients' quality of life improves. In terms of effectiveness, scalp cooling seems to get good performance in its aim to prevent hair loss in patients receiving chemotherapy. The weighted average results of all identified studies indicate that this technology allows for 63.5% of patients to have a good preservation of their hair. In studies with a group of control, the weighted rates of good preservation of the hair are 50.6% with scalp cooling and 16.3% without. From the standpoint of safety technology, the main risk is that of scalp metastases. However, no study has successfully demonstrated a statistically significant difference between groups of patients receiving chemotherapy with or without scalp cooling.

The perspectives of renal cell carcinoma (RCC) treatment have improved with the development of targeted molecular therapies against VEGFR/VEGF-mediated angiogenesis and mTOR. Antiangiogenic drugs, including bevacizumab (in association with IFN-α), sorafenib, sunitinib and pazopanib have demonstrated benefits for patients in terms of life expectancy, with progression free survival and overall survival exceeding 10 and 24 months, respectively. Long-term administration of these drugs, over several months or several years, requires the compliance of patients. Phase II/III studies on antiangiogenic-based therapy in RCC showed a high prevalence of fatigue (20 to 56%), whatever the drug assessed, but with the lowest rates observed with sorafenib or pazopanib. Fatigue is considered by cancer patients as the most important secondary effect regarding the impact on their quality of life and, consequently, is expected to compromise the protocol and the efficacy of the treatment. Management of fatigue induced by therapy or the disease is based on patient information, identification and treatment of causal aetiologies, anti-inflammatory therapy when needed and education and psychological support. Anticipating the risk and level of fatigue expected to be associated with cancer therapy by using both reliable and simple tools remains a challenge in oncology practice. The expected overall benefits of these targeted therapies, coupled with daily assessment and management of fatigue induced by the disease or the treatment, will offer new perspectives for patients with RCC. In this purpose, studies in oncology on the reliability of simple tools based on patient reporting and adapted to clinical practice, as well as interventional studies on fatigue management are needed.

In France, cancer affects 1 to 3% of all children and represents the second most frequent cause of mortality among children younger than fifteen. Malignant blood diseases are the most frequently occurring childhood cancers. Although their mortality rate has been tending to decrease, they often seem to develop after "opportunistic" latent infections persist, undetected, in un-eradicated sites that may be of dental origin. This infectious risk, frequently undiagnosed in hospitals, should be of concern to both general dentists and orthodontists.

Antiangiogenic agents may be associated with severe hand-foot reactions (HFR) requiring dose adjustment by oncologists. Many preventive and curative treatments are described in the literature but their efficacy has not been assessed in clinical trials. The aim of this study was to examine information given to patients about HFR and to evaluate compliance with prophylactic therapy for this complication.

Epigenetic gene regulation contributes, together with genetic alterations, to cancer development and progression. In contrast to genetic disorders, the possibility of reversing epigenetic alterations has provided original targets for therapeutic application. In the last years, work has been focused on the pharmacological restoration of epigenetic regulation balance using epidrugs which yield hopes for novel strategy in cancer therapy. Histone acetylation and DNA methylation are epigenetic modifications which have been closely linked to the pathology of human cancers, and inhibitors of both enzyme classes for clinical use are at hands. Novel findings accumulated during the last years both in chemistry and biomedical applications give rise to new targeted treatments against cancer. Since their links with pathogenesis and progression of cancer were recognized, histone methyltransferases emerge as promising therapeutic targets in cancer treatment.

The prevention and the treatment of oestrogen deficiency induced by breast cancer treatments are crucial in the management of patients. The impacts of this deficiency must not be neglected: quality of life impairments inducing eventually premature withdrawal of hormonotherapies, and excess of bone and cardio-vascular morbidities and mortalities, especially in good prognosis young women. Management strategies of short and long term effects of this deficiency are reviewed and discussed here.