Abstracts Ahead of Print | Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Lung Cancer

Journal Name: Recent Patents on Anti-Cancer Drug Discovery

Author(s): Alessandra Bearz, Sara Cecco, Sara Francescon, Francesco Lo Re, Giuseppe Corona, Paolo Baldo*.

 

 

imgpsh_fullsize_anim.png

 

Background: Lung cancer is the most frequent cause of cancer-related death. In the last decades, the introduction of targeted therapies and more recently, of immunotherapy, has led to significant improvements in different outcomes of this malignant neoplasm.

Objective: The present review provides a balanced overview of most recent targeted therapies and immunotherapies patented for the treatment of lung cancer.

Method: An extensive scientific literature and patent databases search were performed to identify peer-reviewed studies containing information on recently patented drugs for the treatment of lung cancer, with a particular focus on their safety data and recently patented combinations.

Results: The development of therapies directed to different pathways involved in the tumor angiogenesis, proliferation, and metastasis has transformed the clinical practice of lung malignancies. Several clinical trials have shown an improvement in terms of progression-free survival and overall survival in patients with advanced/metastatic lung cancer. Safety data, extracted from clinical trials and from the WHO global database of adverse drug reactions (VigiAccessTM database), show that recently patented drugs for the treatment of lung cancer are well- tolerated and most of the adverse events reported are mild to moderate.

Conclusion: Currently, a consistent number of new drugs and combinations have been introduced for the treatment of patients with advanced-stage lung cancer. Safety data remain essential to better assess the long-term risk/benefit ratio of these valuable emerging therapies. The new patents’ development could provide further significant improvements for lung cancer treatment. To read full abstract, please visit: http://www.eurekaselect.com/173895/article

Abstracts Ahead of Print | Safety Profiles and Pharmacovigilance Considerations for Recently Patented Anticancer Drugs: Cutaneous Melanoma

Author(s): Debora Basile, Camilla Lisanti, Maria A. Pizzichetta, Paolo Baldo*, Giulia Fornasier, Francesco Lo Re, Giuseppe Corona, Fabio Puglisi.

 

imgpsh_fullsize_anim (2).png

 

Background: Malignant melanoma is a skin cancer responsible of 90% of cutaneous cancer related deaths. In recent years, breakthroughs in treatment strategy have revolutionized the prognosis both of early and advanced melanoma patients. In particular, treatment with monoclonal antibodies targeting co-inhibitory checkpoints or specific molecular pathways are pawing the way for a new era of promising options, by prolonging survival time of these patients.

Moreover, unlike the chemotherapy that was used until some time ago, these new drugs have a good and more manageable toxicity profile. However, because of the recent introduction in clinical practice of the new agents, there is a learning curve among physicians regarding early recognition and management of the associated side effects.

Objectives: The analysis of the toxicity profiles of the different agents currently studied for the treatment of early and advanced melanoma, and the description of several relevant recent patents in this field, are the aims of this review.

Methods: A systematically conducted review, based on current clinical guidelines and on international Pharmacovigilance databases (AERS-Eudravigilance – WHO Vigibase).

Results: Our systematic analysis outlines a comprehensive overview about the pharmacology, clinical application and safety of recent anticancer drugs to treat melanoma, which can be an essential instrument for health professionals and researchers.

Conclusion: The new oncological therapies against melanoma are based on increasingly specific biological and immunological targets. For this reason, the potential toxicities that are expected from patients would be less relevant than the systemic “classical” chemotherapy. However, the new therapies are not free from the risk of causing adverse reactions, some of which must be managed promptly and appropriately; moreover the multiplicity of the metabolic pathways exposes the new target therapies to relevant potential interactions. This review can help to understand how important it is not to underestimate potential adverse drug reactions related to new targeted therapies. To read the full abstract, please visit: http://www.eurekaselect.com/173896/article

EDITOR’S CHOICE – Management of Adverse Effects from Atypical Antipsychotics

Journal Name: Current Psychopharmacology

Author(s): Ahsan Nazeer*, Joseph L. Calles.

 

Graphical Abstract:

Abstract:

The use of antipsychotic medications presents a trade-off for the treating physician. On the one hand, there is enough literature regarding the efficacy of these medications to support their judicial use, while on the other, chronic and at time impairing side effects are troubling to both physicians and the patients. Extrapyramidal side effects are the hallmark of first-generation antipsychotics, while metabolic side effects including weight gain, diabetes mellitus, and lipid abnormalities are more common with second-generation antipsychotics. This article presents a concise overview of the current literature on antipsychotic-related side effects and treatment options.

 

 

Read more here: http://www.eurekaselect.com/159976/article

Blog ::: The Side Effects of Chemotherapy on the Body

Chemotherapy drugs are powerful enough to kill rapidly growing cancer cells, but they also can harm perfectly healthy cells, causing side effects throughout the body.

The Side Effects of Chemotherapy on the Body

Cancer cells divide more quickly than healthy cells, and chemotherapy drugs effectively target those cells. Unfortunately, fast-growing cells that are healthy can be damaged too. There are many different chemotherapy drugs with the potential for many different side effects. These effects vary from person to person and from treatment to treatment.

Factors that play a role in side effects include other ongoing treatments, previous health issues, age, and lifestyle. Some patients experience few side effects while others feel quite ill. Although most side effects clear up shortly after treatment ends, some may continue well after chemotherapy has ended, and some may never go away.

Chemotherapy drugs are most likely to affect cells in the digestive tract, hair follicles, bone marrow, mouth, and reproductive system. However, cells in any part of the body may be damaged.

Circulatory and Immune Systems

Routine blood count monitoring is a crucial part of chemotherapy. That’s because the drugs can harm cells in the bone marrow, where blood is produced. This can result in several problems. Red blood cells carry oxygen to tissues. Anemia occurs when your body doesn’t produce enough red blood cells, making you feel extremely fatigued. Other symptoms of anemia include:

  • lightheadedness
  • pale skin
  • difficulty thinking
  • feeling cold
  • general weakness

Chemo can lower your white blood cell count, which results in neutropenia. White blood cells play an important role in the immune system: they help fight infection and ward off illness. Symptoms aren’t always obvious, but a low white blood cell count raises the risk of infection and illness. People with an immune system weakened by chemotherapy must take precautions to avoid exposure to viruses, bacteria, and other germs.

Cells called platelets help the blood clot. A low platelet count, called thrombocytopenia, means you’re likely to bruise and bleed easily. Symptoms include nosebleeds, blood in vomit or stools, and heavier-than-normal menstruation.

Some chemo drugs can weaken the heart muscle, resulting in cardiomyopathy, or disturb the heart rhythm, causing arrhythmia. This can affect the heart’s ability to pump blood effectively. Some chemo drugs can increase the risk of heart attack. These problems are less likely to occur if your heart is strong and healthy at the start of chemotherapy.

Nervous and Muscular Systems

The central nervous system controls emotions, thought patterns, and coordination. Chemotherapy drugs may cause problems with memory, or make it difficult to concentrate or think clearly. This symptom sometimes is called “chemo fog,” or “chemo brain.” This mild cognitive impairment may go away following treatment, or may linger for years. Severe cases can add to anxiety and stress.

Some chemo drugs can cause pain, weakness, numbness, or tingling in the hands and feet (peripheral neuropathy). Muscles may feel tired, achy, or shaky. Reflexes and small motor skills may be slowed. It’s not unusual to experience problems with balance and coordination.

Digestive System

Some of the most common side effects of chemotherapy involve the digestive tract. Mouth sores and dry mouth can make it difficult to chew and swallow. Sores also may form on the tongue, lips, gums, or in the throat. Mouth sores can make you more susceptible to bleeding and infection. Many patients complain of a metallic taste in the mouth, or a yellow or white coating on the tongue. Food may taste unusual or unpleasant.

These powerful drugs can harm cells along the gastrointestinal tract. Nausea is a common symptom, and may result in bouts of vomiting. However, anti-nausea medications given in conjunction with chemotherapy drugs can help alleviate this symptom.

Other digestive issues include loose stools or diarrhea. In some people, hard stools and constipation can be a problem. This may be accompanied by pressure, bloating, and gas. Take care to avoid dehydration by drinking plenty of water throughout the day.

Side effects involving the digestive system can contribute to loss of appetite and feeling full even though you haven’t eaten much. Weight loss and general weakness are common. Despite all this, it’s important to continue eating healthy foods.

Hair, Skin, and Nails (Integumentary System)

Many chemotherapy drugs affect the hair follicles and can cause hair loss (alopecia) within a few weeks of the first treatment. Hair loss can occur on the head, eyebrows, eyelashes, and body. As troubling as it can be, hair loss is temporary. New hair growth usually begins several weeks after the final treatment.

Some patients experience minor skin irritations like dryness, itchiness, and rash. You may develop sensitivity to the sun, making it easier to burn. Your doctor can recommend topical ointments to soothe irritated skin.

Fingernails and toenails may turn brown or yellow, and become ridged or brittle. Nail growth may slow down, and nails may crack or break easily. In severe cases, they can actually separate from the nail bed. It’s important to take good care of your nails to avoid infection.

Sexual and Reproductive System

Chemotherapy drugs can have an effect on your hormones. In women, hormonal changes can bring on hot flashes, irregular periods, or sudden onset of menopause. They may become temporarily or permanently infertile. Women on chemotherapy may experience dryness of vaginal tissues that can make intercourse uncomfortable or painful. The chance of developing vaginal infections is increased. Chemotherapy drugs given during pregnancy can cause birth defects. In men, some chemo drugs can harm sperm or lower sperm count, and temporary or permanent infertility is possible.

Symptoms like fatigue, anxiety, and hormonal fluctuations may interfere with sex drive in both men and women. So can worrying about loss of hair and other changes in appearance. However, many people on chemotherapy continue to enjoy an intimate relationship and an active sex life.

Kidneys and Bladder (Excretory System)

The kidneys work to excrete the powerful chemotherapy drugs as they move through your body. In the process, some kidney and bladder cells can become irritated or damaged. Symptoms of kidney damage include decreased urination, swelling of the hands and feet (edema), and headache. Symptoms of bladder irritation include a feeling of burning when urinating and increased urinary frequency.

You’ll be advised to drink plenty of fluids to flush the medication from your system and to keep your system functioning properly. Note: Some medications cause urine to turn red or orange for a few days. This isn’t cause for concern.

Skeletal System

Most people—and especially women—lose some bone mass as they age. Some chemotherapy drugs can cause calcium levels to drop and contribute to bone loss. This can lead to cancer-related osteoporosis, especially in post-menopausal women and those whose menopause was brought on suddenly due to chemotherapy.

According to the National Institutes of Health (NIH), women who have been treated for breast cancer are at increased risk for osteoporosis and bone fracture. This is due to the combination of the drugs and the drop in estrogen levels. Osteoporosis increases the risk of bone fractures and breaks. The most common areas of the body to suffer breaks are the spine and pelvis, hips, and wrists.

Psychological and Emotional Toll

Living with cancer and dealing with chemotherapy can exact an emotional toll. You may feel fearful, stressed, or anxious about your appearance and your health. Some people may suffer from depression. Juggling work, financial, and family responsibilities while undergoing cancer treatment can become overwhelming.

Many cancer patents turn to complementary therapies like massage and meditation for relaxation and relief. If you have trouble coping, mention it to your doctor. They may be able to suggest a local cancer support group where you can speak with others who are undergoing cancer treatment. If feelings of depression persist, professional counseling may be necessary.

Courtesy: http://www.healthline.com/health/cancer/effects-on-body#sthash.1ANIgi83.dpuf


Current Cancer Therapy Reviews – Most Cited Article

^A7FA97BF1895366FF0B2B1F9D800FAB141BCE70C1E96D32EA5^pimgpsh_fullsize_distr

 http://bit.ly/1OnylnT

Chinese authors contributions to Bentham’s iournal ‘Current Alzheimer Research’

Pan-Amyloid Oligomer Specific scFv Antibody Attenuates Memory Deficits and Brain Amyloid Burden in Mice with Alzheimer’s Disease

Current Alzheimer Research, 11(1): 69-78.

Author(s): Min Zhao, Shao-wei Wang, Yu-jiong Wang, Ran Zhang, Ya-nan Li, Ya-jing Su, Wei-wei Zhou, Xiao-lin Yu and Rui-tian Liu

Abstract: Amyloid oligomers have a critical function in the pathologic processes of various amyloidoses, such as Alzheimer’s disease (AD), Parkinson disease (PD), Huntington’s disease, prion-related diseases, type 2 diabetes, and hereditary renal amyloidosis. Our previous reports demonstrated that a conformation-dependent oligomer-specific single-chain variable fragment (scFv) antibody, W20, isolated from a naïve human scFv library, can recognize oligomers assembled from α -synuclein, amylin, insulin, A β40/42, prion peptide 106–126, and lysozyme, inhibit the aggregation of various amyloid, and attenuate amyloid oligomer-induced cytotoxicity In vitro. Furthermore, W20 recognized the amyloid oligomers in all types of plaques, Lewy bodies, and amylin deposits in the brain tissues of AD and PD patients and in the pancreas of type 2 diabetes patients. In the current study, we showed that W20 blocked the binding of Aβ oligomers to SH-SY5Y cells, did not bind to heat shock protein, rescued cognitive impairments in APP/PS1 transgenic mice, and interfered with Aβ levels and deposits in mouse brain. These results suggest that W20 may be a promising therapeutic for the treatment of AD.

Access the article here: http://benthamscience.com/journal/abstracts.php?journalID=car&articleID=116831

 

Contributions by Chinese Authors in Bentham Science Journal; Anti-Cancer Agents in Medicinal Chemistry

Baicalin Suppresses Migration, Invasion and Metastasis of Breast Cancer via p38MAPK Signaling Pathway

Author(s): Xiu- Feng Wang, Qian- Mei Zhou, Jia Du, Hui Zhang, Yi- Yu Lu and Shi- Bing Su

Affiliation: Research Center for Traditional Chinese Medicine Complexity System, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Pudong, Shanghai 201203, PR China.

Abstract: Metastasis is the major cause of death in breast cancer patients. In this study, we investigated the effects of baicalin, a natural compound, on cell migration, invasion and metastasis using human breast cancer MDA-MB-231 cell line as model system. Baicalin not only dose-dependently inhibited MDA-MB-231 cells migration and in vitro invasion, but also suppressed the tumor outgrowth and the pulmonary metastasis of MDA-MB-231 cells in xenograft model. Importantly, treatment of baicalin caused little change in body weight, liver and kidney function of recipient animals. Tumorigenesis-inhibitory effect is likely linked to the capability of baicalin to downregulate metalloproteinase (MMP)-2, MMP-9, urokinase-type plasminogen activator (uPA) and uPA receptor (uPAR) expression in MDA-MB-231 cells. As baicalin blocked p38 mitogen-activated protein kinase (MAPK) activity and treatment of p38MAPK inhibitor SB203580 led to the reduction of MMP-2, MMP-9, uPA and uPAR expressions, we concluded that baicalin suppresses the tumorigenecity of MDA-MB-231 cells by down-regulating MMP-2, MMP-9, uPA and uPAR expressions through the interruption of p38MAPK signaling pathway.

Access the article here:
http://benthamscience.com/journal/abstracts.php?journalID=acamc&articleID=111240

Chinese Authors have made substantial contributions to Bentham Science Journal Current Drug Targets:

Journal Name: Current Drug Targets

7-18-2014 9-12-03 AM

Article Title:

Molecular Mechanisms and Treatment of Radiation-Induced Lung Fibrosis

Author(s): Nian-Hua Ding, Jian Jian Li and Lun-Quan Sun

Abstract:

Radiation-induced lung fibrosis (RILF) is a severe side effect of radiotherapy in lung cancer patients that presents as a progressive pulmonary injury combined with chronic inflammation and exaggerated organ repair. RILF is a major barrier to improving the cure rate and well-being of lung cancer patients because it limits the radiation dose that is required to effectively kill tumor cells and diminishes normal lung function. Although the exact mechanism is unclear, accumulating evidence suggests that various cells, cytokines and regulatory molecules are involved in the tissue reorganization and immune response modulation that occur in RILF. In this review, we will summarize the general symptoms, diagnostics, and current understanding of the cells and molecular factors that are linked to the signaling networks implicated in RILF. Potential approaches for the treatment of RILF will also be discussed. Elucidating the key molecular mediators that initiate and control the extent of RILF in response to therapeutic radiation may reveal additional targets for RILF treatment to significantly improve the efficacy of radiotherapy for lung cancer patients.

For more details, visit: http://benthamscience.com/journal/abstracts.php?journalID=cdt&articleID=113785

Article Title: Novel Targeted Therapies to Overcome Trastuzumab Resistance in HER2- Overexpressing Metastatic Breast Cancer

Author(s): Yuan Huang, Peifen Fu and Weimin Fan

Abstract:

Overexpression of the human epidermal growth factor receptor 2 (HER2) is identified in approximately 25- 30% of breast cancers and indicates a poor prognosis. Trastuzumab, the anti-HER2 monoclonal antibody (mAb), has shown significant clinical effects selectively in HER2-overexpressing metastatic breast cancer (MBC) with improved overall survival and reduced recurrent risk. However, there is an urgent need to develop new strategies to overcome innate and acquired trastuzumab resistance, which has increasingly occurred. Recently, an increased understanding of mechanisms of trastuzumab resistance significantly promotes the development of novel targeted therapies for trastuzumabrefractory disease. It is believed that aberrant activations of several signaling pathways involving the human epidermal growth factor receptor (EGFR/HER) family, phosphoinositide 3 kinase/Akt (PI3K/Akt) pathway, and vascular endothelial growth factor (VEGF) family, contribute to the development of trastuzumab resistance. Novel agents that target these relevant signal pathways provide some potential solutions, such as tyrosine kinase inhibitors (TKIs) and mAbs. HER2 is also recognized as an immunotherapeutic target. The failure to induce immune-mediated antitumor response is another important reason for trastuzumab resistance. Strategies to boost T cell-mediated immune responses specific to HER2 including HER2 vaccines and bispecific antibodies (bsAbs) could be developed as a promising way to prevent relapse or combat trastuzumab resistance. In this review, the emerging data from preclinical and clinical studies related to these novel therapies will be discussed.

Article Title: Improving the Embryo Implantation Via Novel Molecular Targets

Author(s): Jingjie Li, Xiaoyan Liang and Zijiang Chen

Abstract:

With the development of modern assisted reproductive technology(ART), the treatment of infertility and the pregnant outcome by ART have been significantly improved. However, implantation failure, particularly the unexplained repeated implantation failure (RIF), is still the unsolved and principal problem to affect the outcome of ART. The completed embryo, the receptive uterus and a series of precisely controlled molecular events between the blastocyst and endometrium are all indispensable for the success of implantation. Thus, deep insight into the molecular mechanisms that impact the endometrial receptivity and embryo implantation is an effective way to improve the implantation rate. Here the novel molecular targets and biomarkers have been reviewed that are reported and proved during more recent years in the aspects of ion channels, aquaporins, long noncoding RNAs and microRNAs, kruppel like factors, metabolism related molecules and the endogenous retroviruses. Evaluation of implantation markers may help clinicians to predict pregnancy outcome and detect occult implantation deficiency. Moreover, these novel molecular targets are expected to apply to the clinical practice from bench to bedside and improve the implantation efficiency in ART and natural conception.

Article Title:

Recent Developments in the Discovery of Novel Antipsychotic Agents Modualating Dopamine and Serotonin Receptors

Author(s): Xin Li and Shutao Ma

Abstract:

Currently, schizophrenia, as a serious psychiatric disorder, continues affecting the quality of life in the psychotics. This disease is often debilitating and chronic, showing broad symptoms at one end by hallucinations, delusions, thought disorder and the other end by affective flattening, catatonia, social isolation. In order to combat this disease, many antipsychotic drugs have been developed and introduced into clinical practice in the past half century. However, only a small minority of them can treat effectively schizophrenia without side effects. In view of this situation, high attention has been given to the exploration of desired antipsychotic agents influential especially through the modulation of dopamine and serotonin receptors with substantial strides made in recent years, leading to the discovery of many novel chemical entities with intriguing profiles. In this review, we summarize novel structural antipsychotics in development and discuss the future direction of ideal antipsychotic drug candiates. In particular, the promising atypical antipsychotic profiles of new molecules and the inspirations for their design are highlighted.

%d bloggers like this: