Antimalarial Drug Proven Very Effective In Killing Tumor Cells 

Researchers at the Perelman School of Medicine, the Abramson Cancer Center, and the School of Arts and Sciences at the University of Pennsylvania, have discovered a new way to fight cancer. Scietists have developed a new drug, called Lys05, which proved effective in killing cancer cells in mice.

It seems that the mechanism of action of the new drug consists of blocking the process of recycling in cancer cells, thus interfering with autophagy. Recently, studies have shown that autophagy can be one of the targets that can be used to stop tumor growth. Autophagy, ie self eating, is a protective process that allows cells to survive during starvation. During starvation, autophagy allows cells to degrade proteins and other molecules and use them as an energy source. Autophagy is a genetically programmed process mediated by lysosomes, intracellular organelles. In conditions of starvation, a double membrane vesicle is formed that includes particles to be “eaten”, and then it merges with a lysosome.

Ravi K. Amaravadi, MD, assistant professor of Medicine, and colleagues, demonstrated in previous studies the role of hydroxychloroquine, an antimalarial drug in cancer treatment. Hydroxycloroquine proved useful not only as an antimalarial drug, but also in autoimmune diseases such as Sjogren’s syndrome, rheumatoid arthritis, lupus, etc. Also hydroxycloriquine by inhibiting the activation of dendritic cells from skin, reduces inflammation. Regarding cancer, it seems that hydroxycloroquine  can reduce the autophagy of  cancer cells. In addition, this drug enhances the effect of chemotherapy. However, hydroxycloroquine can not always be used as doses proven effective against cancer are too high. Therefore, Ravi K. Amaravadi teamed up with Jeffrey Amaravadi Winkler, PhD, the Merriam Professor of Chemistry, to develop a new molecule, derived from cloroquine, which can be used in cancer treatment.

Starting from the basic molecule of hydroxycloroquine (cloroquine), researchers have synthesized a new molecule, called Lys05, which has antitumor effects in mice at non-toxic doses. Chemical synthesis and biological evaluation are described in detail in the early edition of the Proceedings of the National Academy of Sciences. Unlike hydroxycloroquine, this new molecule was proven to be effective in reducing tumor growth in the absence of other therapies.

“This single-agent anti-tumor activity suggests this drug  may be even more effective in patients than hydroxychloroquine.” Amaravadi said. He added that Lys05 acts predominantly in cancer cells and on  healthy cells has little or no effect. He also added that Lys05 Amaravadi should be the subject of further studies before being tested on humans.

Myelodysplastic Syndromes

Myelodysplastic syndromes (MDS) are a group of disorders due to clonal proliferation of an abnormal stem cell, resulting in quantitative and qualitative hemopoietic abnormalities, with varying degrees of cytopenia in one or more cell lines, as a result of a marrow replacement by the malignant clone. Bone marrow remains normo or even hypercellular.

MDS are disorders at the border between refractory anemia and leukemia, they arise usually after 50 years of age and their incidence has increased during the last years. By etiology,  they are classified in primary MDS, in which genetic mutations seem to play a major role and secondary MDS – due to exposure to alkilating agents and radiation.

The pathophysiologic mechanism is defective maturation coupled with enhanced proliferation of precursor cells.The indolent course of these diseases is due to coexistence of normal and abnormal (clonal) hemopoiesis. When maturation is totally blocked, the disease merges into acute leukemia.

Diagnosis is based on the presence of dysplasia in the blood and marrow cells.

Myelodysplastic Syndromes Classification

FAB classification (French-American-British):

Refractory anemia (RA)

• <1% blast cellsin the blood , <5% blast cells in the marrow and <15% ringed sideroblasts;
• usually assocated with neutropenia and/or thrombocytopenia (“refractory cytopenia”);
• in the marrow: diserythropoiesis, dismegakariopoiesis with or without disgranulopoiesis.

Refractory anemia with ringed sideroblasts (RARS)

• presence of 1% blast cells in the blood, <5% blast cells in the marrow and <15% ringed sideroblasts (characteristic for this type);

• may be classified in:

-“pure” sideroblastic anemia  – characterized by diserythropoiesis and rare transformation in acute leukemia;

-RARS – characterized by diserythropoiesis, disgranulopoiesis, and/or dismegakariopoiesis, evolution into acute leukemia common.

Myelodysplastic Syndromes

Refractory anemia with excess blasts (RAEB)

• presece of <5% blast cells in blood;
• marrow blasts 5 to 19% with a variable percent of ringed sideroblasts;
• dominant morphological feature is disgranulopoiesis;
• high rate of leukemic transformation.

Refractory anemia with excess blasts in transition (RAEBT)

• transition form between RAEB and acute leukemia;
• 5-29% blasts in blood, marrow blasts: 20-29%;
• Auer rods may be present.

Chronic myelomonocytic leukemia (CMML)

• <5% blasts and monocytes >1000 ul in blood(absolute monocytosis with leukocytosis is definitory for this entity);
• in the marrow: immature myeloid and erythroid precursor cells;
• regarding its clinical and laboratory features (hepatosplenomegaly, leukocytosis, occasionally myelofibrosis) this entity seems t be related more closely to the myeloproliferative disorders. Its classificaton in the MDS group is disputable.

Myelodspalstic Syndrome’s Signs And Symptoms

A few years before developing a MDS, patients may present macrocytic anemia and a mild thrombocytopenia or neutropenia but with no evidence of megaloblastic anemia. This anemia usually results in fatigue and malaise. In patients with cardiac problems may occur signs of chronic heart failure. Due to the low platelet count, patients may have nose and gum bleeding, petechiae and ecchymoses. Moreover, neutropenia may cause all sorts of bacterial and fungal infections associated with symptoms such as fever, dysuria, cough or even shock.

Myelodysplastic Syndromes Symptoms

After being diagnosed, patients with MDS most often manifest their severe thrombocytopenia as epistaxis, gum bleeding, petechiae and echymoses. Also may occur blood in stools and urine. The severe anemia is represented by the pallor of the skin, fatigue, tachycardia or even heart failure in those cases where underlying heart problems were present. Neutropenia causes fever and infections; the most common infections are pneumonias and urinal tract infections.

Osteoporosis

Scientists from the The Institute of Aging Research, a part of the Harvard Medical School, are the authors of a new large meta-study. During their study they have discovered numerous genetic variants that are connected to a higher risk of osteoporosis in specific patients but are also connected to other bone-breaking disorders.

The study was published on the 16th of April in the journal Nature Genetics and reports a number of 56 different genetic variants that were found to be connected to the BMD (Bone Mineral Density – the main indication for osteoporosis).

A number of fourteen genetic variants have been proven to be connected to a higher risk of bone fractures. This study is the first one to discover so many genetic variants to be linked with a high risk of bone fractures.

The importance of the study is due to the fact that almost 1.5 million fractures every year are caused by osteoporosis. Moreover, women aged 65 or more who suffer a fracture at the hip level have a higher risk of death than women who suffer from breast cancer. In addition to this, women over the age of 80 who suffer from the same type of hip fracture, are most likely to die within a year from the time they suffered the fracture.”This is the largest osteoporosis genetic study ever done”, said professor Douglas P. Kiel M.D., who is also the Director of the Musculoskeletal Research Center. He added that the goal of this study is to develop a personalized genetic treatment for patients suffering from osteoporosis while also better understanding the risk factors that are involved in the development of the disease.

Hip Fracture

The study was led by several international scientists, including Dr. Kiel and Dr. Yi-Hsiang Hsu. It involved more than a hundred scientists from all over the world. The data was gathered through 17 different studies conducted in separate parts of the world, whilst having the same subject: Bone Mineral Density of the spine and of the hip. The European Union funded for some of the resources used in the individual studies.

More than one hundred thousand patients participated in the meta-study. The data collected from the 17 studies came from almost thirty-three thousand patients. This data was then replicated with the help of another fifty thousand patients that participated in 34 other studies. All of the patients participating in these studies received bone density scans and underwent genotyping tests. The gathered data was then compared with data gathered from thirty-one thousand patients with a fracture history and almost one hundred thousand control patients.

The current meta-study identified 32 new genetic variants that are connected to the level of BMD. This comes as an addition to the 24 genetic variants that have already been discovered in previous studies. BMD is currently the most accurate predicting factor for fracture risk.

An extract from the study relates that “Results indicate that hundreds of variants with small effects may contribute to the genetic architecture of BMD and fracture risks”.

Dr. Kiel has announced that the Consortium of researchers from around the world that worked for the current study have already planned the next study. The future study will study the genetic variants that are connected to a higher fracture risk instead of more bone density research. Dr. Kiel believes that the fracture risk could be related to other factors besides bone density.

Genetically Engineered Stem Cells Capable Of Fighting HIV Infection

In continuation of a previous study that showed that the stem cells from humans could be used to fight cells infected with HIV, after being properly genetically engineered, researchers from the University of California, Los Angeles (UCLA) have proven the theory correct.

A new study published today in the journal PloS Pathogens shows that genetically engineered stem cells are very effective against HIV infected cells found in the living tissues. The tests have been conducted on laboratory animal models.

“We believe that this study lays the groundwork for the potential use of this type of approach in combating HIV infection in infected individuals, in hopes of eradicating the virus from the body”, said lead investigator and assistant professor Scott G. Kitchen.

In the precedent study, researchers used the CD8+ T cells (also known as cytotoxic T cells or killer T cells) from an HIV positive patient and managed to identify the T cell receptor. This receptor is responsible for the guidance of the T cells towards the HIV-infected cells. Although capable of destroying these infected cells, the T cells are not found in enough quantities in order to be effective in clearing the infection from the organism. Having identified the receptor molecule, researchers were able to clone it and use it to genetically create new human stem cells. Afterwards, they injected these new stem cells into human thymus tissue that was already implanted into an animal model, thus allowing scientists to further observe the reaction in a living organism.

HIV

The result was that a large population of multi-functional CD8+ T cells that were specifically engineered to target HIV-infected cells developed from the stem cells. Scientists also observed that receptors were only specific for the patient from which they were extracted. This is similar to the way an organ can only be transplanted to a specific patient.

In order to formulate these results, scientists used genetically engineered stem cells that were capable to form mature CD8+ T cells. These newly formed CD8+ T cells specifically attacked HIV in various tissues. Researchers used a humanized laboratory mouse, where the HIV infection has similar properties as the human HIV infection.

The peripheral blood, the plasma and some organs from the laboratory mouse were tested for the first time after two weeks and the second time after six weeks. The results of the tests showed that the levels of HIV found in the blood had decreased significantly while the levels of CD4+ T cells (also known as T helper cells) had increased. These levels indicate that the newly engineered stem cells were capable of fighting the HIV infection.

However, scientists noted that there is a possible downside to this new study. They say that the immune system of the laboratory mouse was almost completely reconstructed. Due to this reconstruction, HIV might have mutated slower in the mouse that in would normally mutate in a human. They conclude that these genetically engineered cells may need further adjustment to reach a higher potential in human HIV infections.

“We believe that this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people”, said professor Kitchen.

Congenital Birth Defects

A study conducted by researchers at Sydney’s Victor Chang Cardiac Research Institute and published in the journal Cell, reveals the cause of congenital defects in newborns. According to the study, it seems that hypoxia combined with a genetic defect during pregnancy increased 10-fold risk of developing an abnormality during embryogenesis. During hypoxia tissues are not sufficiently oxygenated and such disturbances influences the cell and its metabolism. Hypoxia can be caused by several factors in pregnancy, such as uncontrolled diabetes, smoking, altitude, certain medications and anemia. Anemia leads to hypoxia because there is not enough red blood cells to carry oxygen to tissues.

Birth Defect

The discovery made by Australian researchers not only clarify the cause of abnormalities but also why they appear only in some people and not others. Professor Sally Dunwoodie, head of the Embryology Laboratory at the institute, Professor at the University of NSW and senior author on the study, said that this discovery clear up many issues so far unclear to scientists. Researchers reached this conclusion by analyzing cases with congenital scoliosis, a deformity of the spine that occurs in 1 in 1000 children. Scoliosis can and gained, especially during childhood, but most shows a genetic predisposition. Scoliosis is characterized by a deviation in the frontal plane spine accompanied by vertebral rotation.

Researchers have found that this combination of factors, ie hypoxia and genetic factors, increased 10-fold risk of developing congenital scoliosis.
This discovery is a step forward in preventing and treating birth defects. By discovering the causes, situations that lead to hypoxia during pregnancy  can be avoided and thus can be removed one risk factor. “We hope it will eventually lead to the development of therapeutics to stop tissue defects occurring in the first place.” Said Professor Sally Dunwoodie.

Scientists began by investigating people who had only one functional copy of the gene that causes congenital scoliosis. This was a major risk factor. Then the researchers put to test in mice. Besides genetic factors,  it was added the second one, hypoxia, that is rats were exposed on day 21 of pregnancy to 8 hours of low oxygen. Michael Davies, the epidemiologist and senior research fellow in the Discipline of Obstetrics and Gynaecology at the University of Adelaide, explained that oxygen has different effects on the embryo and then the infant in various stages of development. Excess oxygen in the newborn may even cause blindness. Similarly, excess oxygen in early pregnancy can have negative effects. In the third trimester of pregnancy, things are reversed.
One explanation given by Professor Bob Graham, Executive Director of the Victor Chang Cardiac Research Institute, was that not as hypoxia as other environmental factors as anemia, can trigger abnormal gene to be  activated. Important to note that mothers who have family history of congenital diseases to be extremely careful during pregnancy.

Esophageal Cancer

According to a study conducted by researchers at Karolinska Institutet and published in the Journal of Clinical Oncology, patients operated for esophageal cancer have long-term health problems in postoperative and quality of life and is well below the national average.

Esophageal cancer is one of the most aggressive cancers and the main therapy  is esophageal resection. There are several surgical procedures depending on cancer location: if located mediotoracic the treatment consists of esophagectomy with lymphadenectomy , but if it is located at the esogastric junction, the stomach also has to be removed. Apart from surgery, there are also other therapies that can help  in the fight against esophageal cancer, such as chemotherapy and radiotherapy.

Esophageal Cancer Surgery

Histologically, esophageal cancer is of several types, but most common is squamous cell carcinoma and adenocarcinoma. Causes of the esophageal cancer are mainly related to diet (smoked foods, canned), but there are certain lesions with an increased risk of malignancy, such as Barrett’s esophagus, namely the appearance of islands of islands of intestinal metaplasia of the esophagus by the action gastro-oesophageal reflux.

In terms of symptoms, they appear relatively late and are nonspecific. Dysphagia, difficulty swallowing meaning seems to be the most common symptom, followed by heartburn (burning retrosternal pain character), abdominal discomfort, weight loss, hoarseness, cough. Therefore, esophageal cancer is usually found in late-stage and surgery, if it is suitable for this type of treatment, is an extensive operation, requiring sometimes a triple approach, thoracic, abdominal and cervical. Out of 25-30% of those undergoing surgery, only one-third have a period of 5 years survival. The quality of life in patients operated is well below the national average.

The study was conducted on 141 patients who had surgery for cancer of the esophagus and had a survival of at least 5 years postoperatively. The  purpose of the study was to assess the quality of life of patients operated for esophageal cancer who had postoperative complications compared with those who had not  such complications. Study results showed that nearly 45% of them had at least one serious health problem after surgery (postoperative infection or chronic respiratory failure).

In order to asses the quality of life, patients were given questionnaires that were completed periodically to 6 months, 3 years and 5 years. The questions focused on patients functional capacity (social life, the physical) and symptoms. Responses were then processed and scientists made a comparison between those who had at least one serious postoperative complication and those who had no complications. Most often, patients complained of dyspnea, fatigue, eating disorder, insomnia and heartburn.

Diet Or Eating Disorder?

Eating disorders are usually complex and their treatment requires a considerable effort. But with a little help you can get rid of them. Anorexia, bulimia and binge-eating disorder or compulsive eating are diseases of the mind, body and spirit and, therefore, all these categories of dysfunctions must be addressed separately for the treatment to be effective. Some people think that removing bad eating habits and correcting symptoms leads to a total cure. However, eating disorder treatments are more complex than usually people think.

Eating Disorder

Types of eating disorders

There are three types of eating disorders: anorexia nervosa, bulimina nervosa and eating disorders of unspecified type. Binge-eating disorder or compulsive eating is placed in the last category. The person with anorexia will lose weight at least 15% of normal body weight, restrict eating and experience amenorrhea (in women). Binge eating disorder is very similar to bulimia, but bulimia is characterized by recurrent excessive eating followed by compensatory behaviors. In contrast, binge-eating disorder sometimes alternates restrictive eating, without the characteristic behaviors of bulimia: vomiting, excessive exercise, abuse of laxatives, diuretics or diet pill use. There is nothing unusual for someone with anorexia or bulimia to progress to binge-eating disorder at some point or someone with these problems to become anorexic.

Eating Disorders Causes

The most powerful trigger that underlies eating disorders are weight loss diets. Those who have never followed any diet, nad never kept track of meals taken, are less likely to develop an eating disorder and are more likely to maintain normal body weight.

How foods are consumed turns them into good or bad foods.

Diets affect the metabolism and making it a habit to follow weight loss regimes, could lead to obesity induced by diet. Metabolism will slow down in order to adapt to low food consumption. When you return to a normal diet, you will win back any lost weight, and sometimes even more. Researchers have already proven that more than 95% of people who are dieting, gained back about every pound they lost. Studies show that yoyo effect is one of the most harmful for the body, compared with a slight overweight status. The human body strives to achieve ideal weight, which in reality is not that right, but the person wants to achieve it. Family history, culture and race are the most important factors for size and body shape. Attempts to change what was scheduled in the building of a people may be unnecessary and unrealistic.

Eating Disorders Symptoms And Treatment

Here are some signs and symptoms that may clarify whether or not a person suffers from an emerging or existing eating disorder:

The person present a history of multiple weight loss diets, which may alternate with periods of overnutrition or total lack of alimentation.

The urge to lose weight even if the person is underweight.

Desire to skip meals when loved ones are persistent in meal or if a person lies that he has eaten earlier, or in another place to sneak away and not eat.

Consuming lots of food during mealtimes and vomiting afterwards in order to remove them.

Use of laxatives, diuretics, diet pills, not to gain weight.

A person’s desire to hide when they eat at night.

Pain in the stomach, diarrhea, constipation or other gastrointestinal problems.

Physical activity that lasts for hours.

Extreme changes in mood.

Expressing the desire to die or to kill a person because she is not happy.

Dealing with interpersonal difficulties in taking decisions, social isolation, impaired concentration, memory and sleep;

Eating

Presence of chest pain, heart, throat, muscle cramps, dental problems, feeling cold. If you notice any of these symptoms in a known person, try to understand, aid him and try not to blame. Initially the sick persons may feel that others want to control their lives and feel ashamed thinking that people will find them skinny. You should not give even if the problem is denied by the sick person.

How to overcome eating disorders

A treatment which involves a team of professionals (therapists, nutritionists, health professionals) can provide the best solutions to overcome eating disorders. When health problems are chronic or acute, hospitalization or intensive rehabilitation programs may be required. When it is for the benefit of the patient, family and loved ones support can provide a better prognosis in terms of recovery. Discovering the real problems that are underlying the condition may be needed, with qualified assistance. Early intervention for these kind of problems is very important.

How can I avoid eating disorders?

The restless, misinformation, lack of time, consumption of too many snacks or fast-food meals can jeopardize a person’s health. It would be advisable to cook as many dishes and meals to be taken with the whole family.The parents are encouraged to conice children to do as much exercise as possbile, to teach them some basic facts about nutrition and to inform them as much as possible. Researchers have confirmed that children who participate in family meals perform better in school and are less likely to use drugs or alcohol. Children who acquire healthy habits at an early age, were less likely to exhibit eating disorders.

Study Shows Higher Mortality Rate In Obesity Linked To Sleeping Pills

A new study published Friday reports that sleeping pills appear to be connected to the increased risk of death amongst patients suffering from obesity. The study reveals that even patients who have 18 or less pills prescribed during the whole year present a higher risk of mortality. The study received funding from the Scripps Health Foundation.

“The associations between sleeping pills and increased mortality were present, and relatively stronger, even in people aged 18 to 54,” said Dr. Robert Langer, family physician, at the EPI/NPAM meeting held in San Diego this March. Co-author of the study, Daniel Kripke, psychiatrist, added that the increased mortality rate of obese patients could be related to sleep apnea, noting that previous studies have shown that sleeping pills are associated with more often and longer pauses in breathing during sleep apnea.

According to Dr. Langer, the use of sleeping pills by patients suffering from obesity is linked with an extra death per year for every 100 patients. A connection between the sex of the patients has also been discovered, showing that men who take sleeping pills have an increased risk of mortality (almost 50 percent higher) than women, after excluding other influential factors.

The current study was conducted by the Scripps Clinic, included almost 40,000 patients and was published for the first time in late February in the journal BMJ Open. The study showed for the first time that most widely used hypnotic drugs were associated with an increased mortality rate amongst patients.

Sleeping Pills

Until now, scientists believed that these hypnotic drugs are safer than the precedent ones because of a shorter duration of action, but the study reveals that their side effects are no different from the drugs that were replaced.

According to an oral session held by Dr. Langer during the AHA (American Heart Association) conference, patients suffering from obesity whilst also having a BMI of over 38 showed an increased risk of mortality. Findings show that the risk of mortality of these patients was almost 8 time higher than that of patients with the same obesity problems but who were not taking hypnotic drugs. The risk of death was shown to be 9.3 times higher in patients who took more than 132 sleeping pills every year.

Over the past several years, the pharmaceutical industries focusing on the development of hypnotic drugs have seen an increase of almost 23 percent in the United States whilst generating almost $2 billion in annual sales.

Data for the current study was gathered in an electronic database over a period of more than 10 years, thus allowing researchers to study approximately 40,000 patients from around the United States. The patients included in the study consisted of two groups. The first group consisted of patients who had been taking hypnotic medication for an average of 2.5 years, whilst the second group consisted of patients who were not prescribed any drugs, thus making up the control group.

Lawrence E. Kline, co-author of the study, said that the results of the study are based on observational data, thus being possible that other factors, which were not counted for, could stand behind the results. He also added that the current study should convince  doctors to prescribe alternatives to hypnotic drugs in order to avoid a higher mortality rate amongst patients.

Recent tests conducted by the Viterbi Family Sleep Center show that cognitive therapy can be useful for patients suffering from insomnia. Tests have also shown that these patients could require less than eight hours of sleep per night. Dr. Kline suggest that better sleeping habits, relaxation and the correct understanding of the body’s natural clock can be helpful for patients suffering from sleeping disorders. He also added that insomnia that resulted in response to different problems, such as depression, should be treated as a psychological disorder, and not through the prescription of hypnotic drugs.

Vemurafenib  Effective Against Metastatic Melanoma

According to a study led by an international team of researchers from the United States and Australia and researchers at Moffitt Cancer Center in Tampa, vemurafenib (PLX4032), an oral BRAF inhibitor, prolongs lives of patients with metastatic melanoma. After Phase II clinical trial, patients with the BRAF mutation had a higher response rate.

Malignant melanoma is an aggressive form of cancer that arises either from a mole or nevus, either from clinically normal skin. The incidence is increasing lately and it seems that solar radiation is one of the causes of this cancer. Other factors incriminated in the occurrence of this cancer are burns, trauma, ionizing radiations. It is important to note that this type of cancer cells occurs when a mole changes its shape, color, or when it begins itching or bleeding.

Melanoma has a high capacity to metastasize, both via lymphatic and hematogenous pathway. Excision of tumor in oncologic safety limits, with or without lymphadenectomy is considered the most important therapeutic gesture.
Vemurafenib is a drug approved by FDA in August 2011 as monotherapy for the treatment of metastatic melanoma in patients with BRAF V600 mutation. Important to note that vemurafenib is not indicated if patients do not express this mutation. Paradoxically, vemurafenib cause tumor growth in such cases. Regarding side effects, there were reported arthralgia, skin rash and photosensitivity.

Vemurafenib Pills

According to study co-author Jeffrey S. Weber, MD, Ph.D., director of the Donald A. Adam Comprehensive Melanoma Research Center at Moffitt, about 50% of patients with melanoma have threonine protein kinase B-RAF mutation, which means therapeutic options for these patients are limited. Dr. Weber said that few patients with this mutation respond to treatment and the average survival is 10 months. However, study results are positive so far because it demonstrates extended survival of patients with more than six months.

Researchers conducted a multicenter Phase II study  on 132 patients aged over 18 years, diagnosed with stage IV melanoma who had at least one previous systemic therapy. The response rate was 56% and was higher than the rate of response to previous therapies such as monoclonal antibody with impilimumab. Dr. Weber pointed out that the study clearly showed that vemurafenib has antitumoral activity in metastatic melanoma and response rates are higher than the therapies used so far.

The study authors  added that one of the main problems is the appearance of cancer resistance to treatment. Therefore, scientists seek to develop new strategies in order not resistance to this drug.