High-dose intravenously (i.v) vitamin C in cancer patients is controversial. Numerous studies carried out on cancer cell lines and animal models demonstrated that millimolar vitamin C concentrations inhibit tumor cells viability, especially in association with chemotherapy. In cancer patients, high-dose i.v vitamin C in monotherapy does not show any anti-cancer activity. Clinical trials assessing high-dose i.v vitamin C concomitantly with chemotherapy do not conclude to reliable evidence for tumor control or overall survival benefit. Randomized double-blind trials are warranted.

In last years, the therapeutic arsenal against breast cancer increased considerably with the arrival of signaling pathway inhibitors, immunotherapy, PARP inhibitors, tyrosine kinase inhibitors and antibody-drug conjugates. Consequently, the range of potential adverse events has also widened and differs from the usual chemotherapies and endocrine therapies. Depending on the administered therapy, the same symptoms can be harmless and treated symptomatically or the warning sign of a potential serious complication requiring a rapid action. We therefore discuss in this article the therapeutic role and some typical adverse events of these new therapies.

Chronic myeloid leukemia (CML) is a malignant hemopathy within the framework of chronic myeloproliferative syndromes, predominant on the granular line. Her drug treatment is based on tyrosine kinase inhibitors (TKIs) which inhibit the abnormal BCR-ABL protein kinase that causes CML and thus block the signals that cause cancer cells to multiply abnormally. However, other proteins are also inhibited, so they can cause a wide range of adverse effects (AEs). The objective of this study was to study the prevalence of AEs of TKIs used in the therapeutic management of CML by the hematology department of University Hospital Center (UHC) of Sidi Bel-Abbes in Algeria and that of the ITK discontinuation following an AE.

Tumoral angiogenesis is a key mechanism involved in the growth and spread of cancer cells. The development of angiogenesis inhibitors, particularly those targeting the Vascular Endothelial Growth Factor (VEGF) pathway, has improved the prognosis and survival of many cancer patients since they were approved in 2005 in France. Vascular Endothelial Growth Factor inhibitors have different mechanisms of action, targeting either the ligand (e.g. bevacizumab, anti-Vascular Endothelial Growth Factor monoclonal antibody; aflibercept, recombinant anti-Vascular Endothelial Growth Factor fusion protein), or its receptors such as tyrosine kinase inhibitors (e.g. sunitinib or sorafenib). These treatments can be combined with conventional chemotherapy, or other anti-cancer therapies, and are associated with variable tolerance depending on the patient's clinical condition and comorbidities. Additionally, angiogenesis inhibition may be associated with cardiovascular and/or kidney toxicity and therefore special monitoring is needed during the treatment duration. Development of hypertension and proteinuria are the commonest renal side effects; these are generally manageable and reversible when treatment is stopped. However, more severe toxicities have been reported such as acute kidney injury, glomerular and/or vascular insults such as thrombotic microangiopathy, and more rarely tubulointerstitial damage. The prescribing physician should be aware of these potentially serious. This article describes the mechanisms of action of antiangiogenic agents and their potential toxicities, with particular respect to the kidneys.

The renal toxicity of anticancer drugs is a clinical challenge because of the intrinsic toxicity of some anticancer drugs and because the cancer itself. Indeed, cancer patients are exposed to all types of renal disorders (obstructive, functional, organic because of radiotherapy, paraneoplastic glomerulopathy, thrombotic microangiopathy…). The therapeutic index of anticancer drugs is often narrow and the doses used for optimal efficacy are high. Improving safety requires a better dose adjustment, which depends on the correct evaluation of the renal function. Prevention remains important as the mortality associated with acute renal failure is very high.

New molecular therapeutic approaches have emerged in recent years for advanced gynaecological cancers, including targeted therapies such as poly-ADP-ribose polymerase inhibitors (PARPi). These have demonstrated efficacy in high-grade serous ovarian cancers in patients carrying a mutation in the BRCA gene, which predisposes them to breast and ovarian cancers. Clinical and pre-clinical data suggest that the activity of PARPi inhibitors may not be limited to BRCA mutated tumours and may involve the homologous recombination pathway. These data raise the question of the potential efficacy of PARPi in advanced endometrial and cervical cancers where treatment options are currently limited. At present, there are few data available on the activity of PARPi in endometrial and cervical cancers, but some results seem promising. In this review, we present a synthesis of the available studies concerning PARPi in endometrial and cervical cancer.

Targeted protein degradation (TPD), discovered twenty years ago through the PROTAC technology, is rapidly developing thanks to the implication of many scientists from industry and academia. PROTAC chimeras are heterobifunctional molecules able to link simultaneously a protein to be degraded and an E3 ubiquitin ligase. This allows the protein ubiquitination and its degradation by 26S proteasome. PROTACs have evolved from small peptide molecules to small non-peptide and orally available molecules. It was shown that PROTACs are capable to degrade proteins considered as "undruggable" i.e. devoid of well-defined pockets and deep grooves possibly occupied by small molecules. Among these "hard to drug" proteins, several can be degraded by PROTACs: scaffold proteins, BAF complex, transcription factors, Ras family proteins. Two PROTACs are clinically tested for breast (ARV471) and prostate (ARV110) cancers. The protein degradation by proteasome is also induced by other types of molecules: molecular glues, hydrophobic tagging (HyT), HaloPROTACs and homo-PROTACs. Other cellular constituents are eligible to induced degradation: RNA-PROTACs for RNA binding proteins and RIBOTACs for degradation of RNA itself (SARS-CoV-2 RNA). TPD has recently moved beyond the proteasome with LYTACs (lysosome targeting chimeras) and MADTACs (macroautophagy degradation targeting chimeras). Several techniques such as screening platforms together with mathematical modeling and computational design are now used to improve the discovery of new efficient PROTACs.

Alopecia, although long considered an unavoidable consequence of cancer therapy, currently presents a multifaceted challenge. The knowledge of the physiology of the hair and consequently of the pathophysiology of alopecia has led to show that there is not one but several types of alopecia. Transposed to the world of oncology, different types of alopecia and subsequently molecular pathways have been characterized, allowing a better understanding of the underlying mechanisms. Thus, in patients with cancer, alopecia can be iatrogenic (chemotherapies, endocrine therapies, targeted therapies, immunotherapies, radiotherapy, surgery) or directly the consequence of the disease itself (malnutrition, scalp metastases, paraneoplastic syndromes). Knowledge of the incriminated mechanism(s) could thus make it possible to deploy an appropriate care component, whether on the preventive or curative sides or in terms of supportive care. These are particularly essential regarding the psychological repercussions caused by alopecia, with significant consequences on the quality of life of patients and with a potential impact on treatment compliance. On the preventive side, the last few years have seen the advent of the automated scalp cooling therapy, supported by several randomized clinical trials. On the curative side, several therapeutic proposals are currently deployed or under development in order to provide relevant treatments.

"Targeted therapies and pathophysiological mechanisms of proteinuria Targeted therapy represents a promising therapeutic approach for patients with diverse cancers and has enabled significant development in medical oncology. This new class of anticancer drugs includes antibodies, fusion-proteins and receptor tyrosine kinase inhibitors among others. Depending on their molecular targeting, side effects can affect multiple organs, especially the kidney. Antiangiogenic agents inhibit the VEGF/VEGFR pathway resulting in reduction of nitric oxide production and alteration of podocytes function, which causes hypertension and proteinuria. EGFR inhibitors are responsible of electrolytic disorders. Hereby, we synthetized the current knowledge on renal toxicities on main molecular targeted therapies. Toxicities management is mainly based on clinical and biological monitoring, which can lead to drug withdrawing or dose adaptation."

"Renal toxicity of antineoplasic agents Renal toxicity of antineoplasic agents is a common complication faced by oncologists and nephrologists whose incidence depends on therapeutic classes used and patient's comorbidities. Nephrotoxicity is variable, according to mecanisms, chronology and potential reversibility. Besides acute kidney injury and/or chronic kidney disease, clinical features include several urinary abnormalities (mainly proteinuria). The onset of renal toxicity may directly compromise vital prognosis and may lead to the interruption of medications affecting cancer-specific mortality. Nephrotoxicity prevention (when feasible) and rapid diagnosis are essential to optimize cancer-patient medical care."

Mucositis is defined as inflammatory and/or ulcerative lesions of the oral and/or gastrointestinal tract. It occurs in approximately 40% to 50% of adults patients receiving conventional chemotherapy and up to 75% of patients receiving high dose chemotherapy as conditioning for hematopoietic stem cell transplantation. It is a toxic side effect, which strongly impairs quality of life and leads to refractory pain, increasing risk of infection and even therapeutic modifications. Despite improvements made, the management of mucositis remains a challenge and is still not consensual. A multicentric survey of practices concerning the preventive and curative management of chemo-induced mucositis in pediatric oncology department in France was carried out using a standardized questionnaire. Results confirm heterogeneous practices and the small progress made during the last decade. This national survey and an analysis of the recent literature leads to propose guidelines for the prevention and treatment of oral mucositis in children receiving treatment for cancer.

New anti-cancer therapeutics have been developed in the recent years and dramatically change prognosis and patient management. Either used alone or in combination, immune checkpoint inhibitors (ICI), such as anti-CTLA-4 and anti-PD1/PD-(L)1, act by removing T-cell inhibition to enhance their antitumor response. This change in therapeutic targets leads to a break in immune-tolerance and a unique toxicity profile resulting in immune complications. These side effects, called Immune-Related Adverse Events (IrAEs), can affect all organs, with a wide range of clinical and biological presentations and severity. Various rheumatic and musculoskeletal manifestations have been reported in the literature, ranging from mild arthralgia, polymyalgia rheumatica, to genuine serodefined rheumatoid arthritis and myositis. Tolerance studies suggest some correlations between IrAEs occurrence and tumor response. Assessment of patient musculoskeletal status prior to the start of the ICI is warranted. Management of rheumatic IrAEs does not usually request ICI discontinuation, exception for myositis or very severe forms where it should be discussed. Treatment relies on non-steroidal anti-inflammatory drugs (NSAIDs) or low dose glucocortioids (<20mg per day). Dose should be adjusted according to severity. The use of disease modifying anti-rheumatic drugs (DMARDs), either conventional and/or biological should be very cautious and result from a shared decision between oncologist and rheumatologist to best manage dysimmunitary complications without hampering the antitumor efficacy of ICI.

The addition of palbociclib to endocrine therapy has been shown to improve progression free survival in hormone receptor positive metastatic breast cancer patients. This cyclin CDK4/6 inhibitor could expose patients to a grade 3-4 hematological toxicity, leading to treatment discontinuation or treatment interruption that is potentially associated with a lack of efficiency. The aim of this study was to identify predictive factors of severe early hematotoxicity (ESHT).

The HER2 receptor (Human Epidermal Growth Receptor 2) is a transmembrane receptor with tyrosine kinase activity that is over-expressed in 25-30 % of breast carcinomas. Its activation is associated with an exaggeration of cell proliferation with an increase in repair capacity resulting in increased radioresistance. On cardiac tissues, HER2 receptor activation plays a cardio-protective role. Trastuzumab, the first anti-HER2 drug used to treat patients with breast cancer overexpressing HER2 receptor , inhibits the cascade of reactions resulting in the proliferation of tumor cells, thus restoring cellular radiosensitivity. However, the combination of Trastuzumab with radiation therapy also removes HER2 receptor cardio-protective role on myocardial cells which increases the risk of cardiotoxicity. Thus, the concomitant association of these two modalities has long been a subject of controversy. Recent advances in radiation therapy technology and early detection of cardiac injury may limit the cardiotoxicity of this combination. Through this review, we developed the biological basis and the benefit-risk of concomitant combination of radiotherapy and Trastuzumab in adjuvant treatment of breast cancers overexpressing HER2 and we discuss the modalities of its optimization.