Rigosertib Shows Promise in EB-Associated Skin Cancer
Rigosertib, a polo-like kinase 1 (PLK1) inhibitor, demonstrated antitumor efficacy in patients with recessive dystrophic epidermolysis bullosa (RDEB) and advanced squamous cell carcinoma (SCC), with an objective response achieved in four of five patients.
METHODOLOGY:
Researchers conducted an open-label, single-arm phase 2 study in Austria and the United States of five patients with advanced, treatment-refractory RDEB-SCC who had failed prior standard of care and were then treated with oral or intravenous (IV) rigosertib.
Participants (median age, 23 years) received either oral rigosertib (560 mg twice daily on days 1-21 of each 28-day cycle for 13 cycles) or IV rigosertib (1800 mg/24 h as a 72-h continuous infusion on days 1-3 of each 14-day cycle for eight cycles, then on days 1-3 of 28-day cycles until 1 year of treatment).
Two patients received IV treatment, two received oral treatment, and one received a combination of both.
The primary outcome was the objective response rate and safety. Quality of life was a secondary outcome.
TAKEAWAY:
Two patients achieved complete a compete response, and two others had partial responses. The fifth patient discontinued treatment early because of unrelated complications.
Rigosertib was generally well tolerated. Most adverse events were urinary-related (cystitis, hematuria) and manageable with dose adjustments or symptomatic treatment.
IN PRACTICE:
'These initial results indicate rigosertib as a promising drug therapy for RDEB-SCC where there is a substantial unmet need and no approved therapies,' the study authors wrote. The study, they noted, was the 'first clinical trial of any experimental cancer therapeutic in this rare and complicated monogenic disease.'
SOURCE:
The study was led by Martin Laimer, Department of Dermatology and Allergology and EB House Austria, University Hospital of the Paracelsus Medical University, Salzburg, Austria, and was published online on May 29 in British Journal of Dermatology .
LIMITATIONS:
Usefulness of imaging techniques in this study was limited, particularly because of the chronic inflammatory response in lesional skin that is inherent to RDEB.
DISCLOSURES:
The study was funded by Debra International through Debra Austria, Debra of America, Cure EB, and Debra UK. Laimer and three other authors reported receiving consulting fees and grants from Onconova Therapeutics, Inc. Two authors declared being employees of Onconova, which provided the study drug.
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Health Line
an hour ago
- Health Line
Is Schizophrenia a Personality Disorder?
Key takeaways Schizophrenia is not a personality disorder but rather a type of psychotic disorder listed in the Diagnostic and Statistical Manual of Mental Disorders under 'schizophrenia spectrum and other psychotic disorders.' Symptoms of schizophrenia include hallucinations, delusions, disorganized thinking, disorganized motor function, and negative symptoms like decreased self-motivation, diminished emotional expression, decreased speech output, social disinterest, and reduced ability to experience pleasure. Unlike personality disorders, which involve long-standing patterns of interactions that impact behavior, schizophrenia involves altered perceptions of reality. It typically presents with psychotic symptoms in adulthood, during the 20s or later in life, with varying frequency and severity of symptoms and episodes mixed with symptom-free periods. Many symptoms associated with mental health conditions can create social isolation, pressure, and a deterioration of relationships. Stigma and fear of judgment may keep you away from peers. Sometimes, the symptoms you're experiencing may contribute to low emotional expression or decreased ability to experience joy through others. Living with schizophrenia can present a number of these challenges, but it doesn't mean you're living with the rigid, long-term patterns of behavior that accompany a personality disorder. Is schizophrenia a personality disorder? Schizophrenia is not a personality disorder. It's a type of psychotic disorder listed in the Diagnostic and Statistical Manual of Mental Disorders, 5 th edition, text revision (DSM-5-TR), under 'schizophrenia spectrum and other psychotic disorders.' Psychotic disorders involve altered perceptions of reality. These experiences make up the symptoms of psychosis, which are key features in all psychotic disorders. Psychotic symptoms include: hallucinations delusions disorganized thinking disorganized motor function negative symptoms What are negative symptoms? Negative symptoms are those indicating a loss of function. They include: avolition (decreased self-motivation) diminished emotional expression alogia (decreased speech output) asociality (social disinterest) anhedonia (decreased ability to experience pleasure) Symptoms of psychosis are primary features of schizophrenia. To receive a formal diagnosis, you must be experiencing delusions, hallucinations, or disorganized thinking for the majority of a 1-month period. According to the DSM-5-TR, schizophrenia typically presents with psychotic symptoms in adulthood, during your 20's, or later in life, depending on your circumstances. Symptoms can vary in frequency and severity and often come in episodes mixed with periods of time where you have no symptoms at all. Unlike schizophrenia, personality disorders don't have to include a component of psychosis. They're identified by long-standing patterns of behavior that impact how you interact with the world around you. Personality disorder characteristics tend to be more long-term and constant. They're often noticed in childhood and become enduring, rigid patterns of thought and action throughout life. Is schizophrenia a multiple personality disorder? In 2008, a survey from the National Alliance on Mental Illness (NAMI) found the greatest misconception surrounding schizophrenia was that it involved multiple or 'split' personalities. According to the report, 64% of Americans believe this to be true. Schizophrenia isn't a multiple personality disorder, but symptoms of psychosis can make it seem like someone has morphed into a completely different person. Hallucinations, for example, can mean hearing voices or seeing people who aren't actually there. Talking out loud at a hallucination might make it seem like you're talking with another 'self.' Similarly, delusions can change aspects of your personality. You might have been a long-term advocate of something only to suddenly cast it aside, due to delusion. Schizophrenia can make you — and those around you — feel as though your personality shifts during symptom episodes. In schizophrenia, however, you're experiencing psychosis, not dissociation, which is the mechanism underlying dissociative identity disorder (previously known as multiple personality disorder). It is possible, however, to be living with both schizophrenia and dissociative identity disorder. What's dissociation? Dissociation is a mental escape mechanism that separates you from reality, often brought on by traumatic experiences. Dissociation is one way your brain tries to protect itself by distancing you from overwhelming memories and circumstances. Schizophrenia vs. schizotypal personality disorder Schizotypal personality disorder is considered a schizophrenia-spectrum disorder. You may have an increased chance of developing this condition if you have a family history of schizophrenia. Despite this link and some overlapping symptoms, these conditions aren't the same. Schizotypal personality disorder in the DSM-5-TR is a Cluster A personality disorder that involves overarching eccentric behaviors and beliefs. Like all personality disorders, schizotypal personality disorder features an inner experience different from cultural norms. It emerges in childhood and contributes to challenges in maintaining close interpersonal relationships. The uncommon behaviors and thoughts in schizotypal personality disorder can be similar to hallucinations and delusions in schizophrenia. Delusions are unwavering beliefs in something that can be proven otherwise. When you're experiencing a delusion, no evidence to the contrary will sway your belief, not even seeing, hearing, or participating in undeniable proof. Schizotypal personality disorder involves nontraditional beliefs; however, they're often related to intangible concepts, like clairvoyance, the paranormal, or superstitions. They're not necessarily rigid or untrue, though they can be. You may also experience unusual sensory perceptions or 'bodily illusions' when living with schizotypal personality disorder. Unlike hallucinations, these sensory distortions involve real stimuli — just misinterpreted. Schizotypal personality disorder symptoms According to the DSM-5-TR, symptoms of schizotypal personality disorder can include: a persistent belief that everything happening is directly related to you magical thinking that influences behavior and decisions preoccupation with paranormal phenomena bodily illusions atypical perceptual experiences uncommon, sometimes metaphorical, speech patterns and thinking paranoid ideation suspiciousness atypical emotional responses (or lack thereof) eccentric behavior unkempt appearance persistent social anxiety even in familiar company Living with schizotypal personality disorder may come with transient or passing psychotic episodes. These reality lapses can last minutes to hours and tend to be in response to stress. If they occur, the DSM-5-TR states they rarely meet the criteria for an additional psychotic disorder diagnosis. Treatment options of schizophrenia vs. schizotypal personality disorder Both schizophrenia and schizotypal personality disorder are lifelong conditions that can involve psychotherapy and medications to help lessen their impact. Medications may be used for both disorders. You may be prescribed: antipsychotics antidepressants anxiolytics (anti-anxiety medications) The medications your healthcare team recommends will be based on your symptoms, but antipsychotics are considered a first-line treatment approach when psychosis is present. Psychotherapy can also help you cope with a schizophrenia spectrum condition, though research is limited on how effective it is for schizotypal personality disorder. Common therapies include: cognitive behavioral therapy (CBT) group therapy compliance therapy meta-cognitive training mindfulness therapy narrative therapy Coordinated specialty care (CSC) might also make a difference in your quality of life. CSC involves a multidisciplinary support network to help you adjust to living and working with schizophrenia. Delusions and skewed perceptions, however, can make it difficult to recognize the need for treatment when living with schizophrenia or schizotypal personality disorder.
Health Line
an hour ago
- Health Line
Types of Schizophrenia
Key takeaways The DSM-5 no longer recognizes schizophrenia subtypes as separate diagnostic categories. However, the five classical subtypes (paranoid, hebephrenic, undifferentiated, residual, and catatonic) can still be helpful as specifiers for treatment planning. Schizophrenia affects approximately 1% of people in the United States, with men typically receiving a diagnosis in their late teens to early 20s and women typically receiving a diagnosis in their late 20s to early 30s. When schizophrenia occurs in children (which is rare), symptoms in older children and teens can include social withdrawal, sleep disruptions, impaired school performance, irritability, irregular behavior, and substance use. Schizophrenia is a chronic mental health disorder that affects: emotions the ability to think rationally and clearly the ability to interact with and relate to others The National Alliance on Mental Illness (NAMI) reports that research indicates that schizophrenia affects close to 1% of people in the United States. Men typically receive a schizophrenia diagnosis in their late teens to early 20s. Women typically receive a diagnosis in their late 20s to early 30s. Episodes of the illness can come and go, similar to the process of remission. When there's an 'active' period, an individual might experience: Current DSM-5 status Diagnostic changes were made for several disorders in the new Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, text revision (DSM-5-TR), including schizophrenia. In the past, an individual only had to have one of the symptoms to receive a confirmed diagnosis Now, a person must have at least two of the symptoms. The DSM-5 also removed the subtypes as separate diagnostic categories, based on the presenting symptom. This was found to not be helpful, since many subtypes overlapped with one another and were thought to decrease the diagnostic validity, according to the American Psychiatric Association (APA). Instead, these subtypes are now specifiers for the overarching diagnosis, to provide more detail for the clinician. Subtypes of schizophrenia Although the subtypes don't exist as separate clinical disorders anymore, they can still be helpful as specifiers and for treatment planning. There are five classical subtypes: paranoid hebephrenic undifferentiated residual catatonic Paranoid schizophrenia In 2013, the APA determined that paranoia was a positive symptom of the disorder. Paranoid schizophrenia was no longer considered a separate condition. However, the subtype description is still used because of how common this symptom is. Symptoms include: delusions hallucinations disorganized speech (word salad, echolalia) trouble concentrating behavioral impairment (impulse control challenges, emotional lability) flat affect Hebephrenic (disorganized) schizophrenia Hebephrenic or disorganized schizophrenia is still recognized by the International Statistical Classification of Diseases and Related Health Problems (ICD-10), although it's been removed from the DSM-5-TR. In this variation of schizophrenia, the individual does not have hallucinations or delusions. Instead, they experience disorganized behavior and speech. This can include: flat affect (inability to display emotions) speech disturbances disorganized thinking involuntary or unexpected emotions or facial reactions trouble with daily activities Undifferentiated schizophrenia Undifferentiated schizophrenia was the term used to describe when an individual displayed behaviors that were applicable to more than one type of schizophrenia. For instance, an individual who had catatonic behavior but also had delusions or hallucinations and disorganized speech might have received a diagnosis of undifferentiated schizophrenia. With the new diagnostic criteria, this merely signifies to the clinician that a variety of symptoms are present. Residual schizophrenia This 'subtype' is a bit tricky. It's been used when a person has a previous diagnosis of schizophrenia but no longer has any prominent symptoms of the disorder. The symptoms have generally lessened in intensity. Residual schizophrenia usually includes more 'negative' than positive symptoms, such as: flattened affect psychomotor difficulties slowed speech limited attentiveness to personal hygiene Many people with schizophrenia go through periods where their symptoms wax and wane (increase and decrease) and vary in frequency and intensity. Therefore, this designation is rarely used anymore. Catatonic schizophrenia Although catatonic schizophrenia had been listed as a subtype in the first Diagnostic and Statistical Manual of Mental Disorders first edition (1952) through the DSM-4 (1994), the DSM-5 removed it as a subtype. Catatonia is now considered a specifier. This is because it occurs in a variety of psychiatric and general medical conditions. Catatonic schizophrenia typically presents itself as immobility, but it can also look like: mimicking behavior mutism (inability to speak) a stupor-like condition (reduced responsiveness) Childhood schizophrenia Childhood schizophrenia isn't a subtype but rather an indicator of the time of diagnosis. A diagnosis in children is fairly uncommon. When it does occur, it can be severe. Early onset schizophrenia typically occurs between ages 13 and 18 years. A diagnosis under age 13 years is considered very early onset and is extremely rare. Symptoms in very young children are similar to those of developmental disorders, such as autism and attention deficit hyperactivity disorder (ADHD). These symptoms can include: language delays late or unusual crawling or walking irregular motor movements It's important to rule out developmental issues when considering a very early onset schizophrenia diagnosis. Symptoms in older children and teens include: social withdrawal sleep disruptions impaired school performance irritability irregular behavior substance use Younger individuals are less likely to have delusions, but they're more likely to have hallucinations. As teens get older, more typical symptoms of schizophrenia — like those seen in adults — usually emerge. It's important to have a knowledgeable professional make a diagnosis of childhood schizophrenia because it's so rare. It's crucial to rule out any other condition, including substance use or an organic medical issue. A child psychiatrist with experience in childhood schizophrenia should lead the treatment team and discussions about its plan. Treatment typically involves a combination approach that can include: Conditions related to schizophrenia Schizoaffective disorder Schizoaffective disorder is a separate and different condition from schizophrenia, but sometimes it gets lumped in with it. This disorder has elements of both schizophrenia and mood disorders. Psychosis, which involves a loss of connection with reality, is often a component. Mood disorders can include either mania or depression. Schizoaffective disorder is further classified into subtypes based on whether a person has only depressive episodes or whether they also have manic episodes with or without depression. Symptoms can include: paranoid thoughts delusions or hallucinations trouble concentrating depression hyperactivity or mania limited attentiveness to personal hygiene appetite disturbance sleep disruptions social withdrawal disorganized thinking or behavior Diagnosis is typically made through a thorough physical exam, interview, and psychiatric evaluation. It's important to rule out any medical conditions or any other mental illnesses like bipolar disorder. Treatments include: medications group or individual therapy practical life skills training Other related conditions Other related conditions to schizophrenia include: delusional disorder brief psychotic disorder schizophreniform disorder
Yahoo
an hour ago
- Yahoo
Truist Financial Maintains Buy Rating on Sixth Street Specialty Lending (TSLX)
In a report released on June 5, Mark Hughes from Truist Financial maintained a Buy rating on Sixth Street Specialty Lending Inc. (NYSE:TSLX) with a price target of $24.00. Sixth Street Specialty Lending Inc. (NYSE:TSLX) reported strong fiscal Q1 2025 results, with an adjusted net investment income of $0.58 per share and a 13.5% annualized return on equity. A Senior Executive staring out of the window of a skyscraper, emphasizing the company's leadership in the financial sector. It also declared a base quarterly dividend of $0.46 per share along with a supplemental dividend of $0.06 per share, reflecting management's confidence in its earning power. Sixth Street Specialty Lending (NYSE:TSLX) is a specialty finance company that lends to middle-market companies, generating current income primarily in United States-domiciled middle-market companies. It does so through direct originations of senior secured loans and, less commonly, originations of mezzanine and unsecured loans and investments in equity securities, corporate bonds, and other instruments. While we acknowledge the potential of TSLX as an investment, our conviction lies in the belief that some AI stocks hold greater promise for delivering higher returns and have limited downside risk. If you are looking for an extremely cheap AI stock that is also a major beneficiary of Trump tariffs and onshoring, see our free report on the best short-term AI stock. READ NEXT: and . Disclosure: None. Error in retrieving data Sign in to access your portfolio Error in retrieving data Error in retrieving data Error in retrieving data Error in retrieving data
