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Study sheds light on why some prostate tumors are resistant to treatment
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Nicole Fawcett, [email protected]
For immediate release
Study sheds light on why some prostate tumors are resistant to treatment
Researchers identify gene program that causes extreme non-response in one-third of patients
ANN ARBOR, Michigan — A new study from University of Michigan Rogel Cancer Center researchers identifies a cellular signature that explains why about one-third of prostate cancers respond especially poorly to treatment.
Treatments such as enzalutamide, which is an androgen receptor pathway inhibitor (ARPI), are standard of care for advanced prostate cancer. While many patients have long-term good response to the drugs, some will derive no benefit whatsoever. These “extreme non-responder” patients die much more quickly from prostate cancer.
The new study, published in npj Precision Oncology, looked at RNA sequencing data and clinical outcomes from several prostate cancer clinical trial datasets. The researchers identified a gene program linked to ARPI extreme non-response. Moreover, they discovered the chemotherapy docetaxel could be a good option earlier on in patients whose tumor harbors the ARPI extreme non-response program. Docetaxel is approved for prostate cancer but typically given later in the course of treatment.
“We found significant differences in the gene expression program between prostate cancers that do exceptionally well vs. exceptionally poorly with ARPIs. Patients who have this extreme non-response program appear to get significant benefit from docetaxel, suggesting these patients may be good candidates for earlier docetaxel treatment,” said lead first author Anbarasu Kumaraswamy, Ph.D., an investigator in the Alumkal Lab at the Rogel Cancer Center.
The researchers also found that the kinase CDK2 regulates the extreme non-response program, and targeting CDK2 could block the program and reduce tumor growth in the laboratory samples that harbored the ARPI extreme non-response program. The authors suggest exploring CDK2 inhibitors, currently in clinical trials in other cancer types, as a promising new direction in prostate cancers with the extreme ARPI non-responder program.
Additional authors: Ya-Mei Hu, Joel A. Yates, Chao Zhang, Eva Rodansky, Dhruv Khokhani, Diana Flores, Zhi Duan, Yi Zhang, Shaadi Tabatabaei, Rachel Slottke, Shangyuan Ye, Primo Lara, Adam Foye, Charles J. Ryan, David A. Quigley, Jiaoti Huang, Rahul Aggarwal, Robert E. Reiter, Max S. Wicha, Tomasz M. Beer, Matthew Rettig, Martin Gleave, Christopher P. Evans, Owen N. Witte, Joshua M. Stuart, George V. Thomas, Felix Y. Feng, Eric J. Small, Zheng Xia, Joshi J. Alumkal
Funding for this work is from Stand Up to Cancer-Prostate Cancer Foundation; Prostate Cancer Foundation; National Cancer Institute grants R01 CA251245, R01 CA282005, R01 CA291986, P50 CA186786, P30CA046592; National Comprehensive Cancer Network/Astellas Pharma Global Development/Pfizer Inc; Joint Institute for Cancer Research; Allen Family; Smith Family; U.S. Department of Defense grant W81XWH2110539; National Institute of General Medical Sciences grant R01 GM147365; National Institutes of Health grant T90 DE030859
Disclosure: None relevant to this work
Paper cited: “Transcriptional profiling clarifies a program of enzalutamide extreme nonresponse
in lethal prostate cancer,” npj Precision Oncology. DOI: 10.1038/s41698-025-01002-8
Resources:
University of Michigan Rogel Cancer Center, www.rogelcancercenter.org
Michigan Medicine Cancer AnswerLine, 800-865-1125
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Heads roll over Swat river tragedy
PESHAWAR:The Khyber-Pakhtunkhwa government has removed top officials of Rescue department and Upper Swat Development Authority following the recent drowning of tourists in the Swat River, said officials on Tuesday.
The provincial inspection team submitted a report blaming the Swat Development Authority for administrative delays, reported Express News.
The report also raised concerns over the DG Rescue’s lack of technical expertise in handling such emergencies.
The incident, in which several tourists drowned due to a delayed rescue operation, had already led the provincial government to suspend six officers earlier.
As part of the latest action, K-P Rescue DG’s services have been handed over to the Peshawar Development Authority (PDA), while the Swat Development Authority DG has been removed from his seat and assigned a non-operational role, effectively removing him from active administrative duties.
Commissioner’s findings
The decisions follow a detailed report submitted by the Malakand commissioner to an inquiry committee investigating the mishandling of the rescue operation.
The Swat tragedy has sparked criticism over lack of emergency preparedness in the region, especially during peak tourist seasons.
The provincial government’s disciplinary action underscores growing concerns over tourism safety and crisis response mechanisms in the area.
According to official reports, 17 tourists — 10 from Sialkot, six from Mardan, and one resident — were caught in floodwaters after entering the river in Khwazakhela despite visible risks.
Four tourists were rescued, while 12 bodies were recovered. Rescue efforts for one missing person are ongoing.
The Provincial Disaster Management Authority (PDMA) described the flood level as “very high”. The sudden surge raised the Swat River’s flow from 6,738 to 77,782 cusecs within hours, leaving little chance for those trapped to return to safety.
An investigation revealed that nearby construction along the river had altered its natural flow, causing deceptively low water levels at the site.
This misled the tourists and they entered the river. A hotel security guard reportedly tried to stop them, but they bypassed the main entrance and accessed the river through the back. Within 14 minutes of entering, rising water levels prompted a distress call at 9.45am.
Rescue teams arrived at 10.05am — 20 minutes after the call. Before the incident, early flood alerts had been issued by the irrigation department at 8.41am.
Formal warnings were sent to the deputy commissioners of Swat, Charsadda and Nowshera, as well as PDMA and other relevant authorities. A formal flood alert followed at 10.30am.
The report noted that Section 144, prohibiting swimming and boating in the Swat River, had been imposed from 24 June, but enforcement remained lax
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Sri Lanka to take legal action against nearly 1,000 for negligence of mosquito breeding-Xinhua
COLOMBO, July 8 (Xinhua) — Sri Lankan health officials have planned to take legal action against 982 individuals for allowing mosquito breeding sites on their properties, the National Dengue Control Unit said on Tuesday.
Preshila Samaraweera, a consultant community physician at the National Dengue Control Unit, told reporters that these breeding sites were identified during a national dengue awareness week between June 30 and July 5.
Health authorities inspected 144,250 premises during the week. They found mosquito larvae at 4,275 locations, Samaraweera said.
Samaraweera said that many schools were identified as potential dengue breeding grounds during the inspections.
As a result, officials will launch a nationwide dengue eradication campaign at all schools on Wednesday. The initiative, called “Clean School,” aimed to eliminate mosquito breeding sites and raise awareness among students and staff. ■
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Texas project to build four nuclear plants is in talks with 'hyperscalers' – Reuters
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Apple Chief Operating Officer COO Jeff Williams to Retire, Sabih Khan to Replace
Apple Inc. Chief Operating Officer Jeff Williams is retiring as the company’s longtime No. 2, marking a major changing of the guard at an already tumultuous time for the iPhone maker.
Williams will step down as COO this month before retiring from the company later in the year, Apple said in a statement Tuesday. He will continue to oversee the design team, as well as manage health initiatives, until his departure. Sabih Khan will replace Williams as COO, while Apple’s design team will shift to reporting directly to Chief Executive Officer Tim Cook.
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Apple (AAPL) COO Jeff Williams to Pass Role to Lieutenant Sabih Khan
Longtime Apple Inc. Chief Operating Officer Jeff Williams will hand off the job to deputy Sabih Khan later this month, marking a major transition for the iPhone maker.
Williams is taking the step as part of a “long-planned succession,” Apple said in a statement Tuesday. He will continue to report to Chief Executive Officer Tim Cook and oversee the company’s design team, as well as managing health initiatives. The design group will begin reporting directly to Cook after Williams retires later in 2025, Apple said.
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Brad Pitt’s new romance with Ines de Ramon a PR stunt?
Brad Pitt’s romance with Ines de Ramon raises eyebrows for THIS reason Brad Pitt has been accused of “staging” romance with Ines de Ramon in order shift public focus away from his highly publicized divorce from Angelina Jolie.
Following the F1 star’s media tours for the promotion of his new movie, some of which Pitt attended with de Ramon, fans have been speculating that Pitt’s relationship with de Ramon may be more of a distraction tactic than a genuine romance.
The Pitt-led movie earned solid numbers at the box office during the first two weeks of its release, however, it wasn’t a smash success, leading critics to conclude it might be linked to his recent finalized divorce from ex-wife Jolie.
Some observers suggested that Pitt’s romance could be a move to distract media attention from his messy past.
As per a report by Radar Online, social media users believed that Pitt and de Ramon were acting up for the spotlight.
“Brad Pitt avoiding Ines kiss (once again) hahaha, she thought he was going to kiss her and he was just trying to cross to the other side, I just can’t,” an X user wrote as per the outlet.
“The way this relationship is so PR I just can’t,” the netzin added.
“He didn’t even want to kiss her again for the third time, he ignores her again like she doesn’t belong with him like a total stranger, it’s hilarious,” a second user noted.
While others even labelled their appearances during media tours as “staged scene(s).”
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Risankizumab Found Effective in Patients With Moderate Plaque Psoriasis
Despite traditionally being excluded from systemic therapy trials, patients with moderate psoriasis—defined as having Body Surface Area (BSA) of 3% to 10% or involvement of high-impact areas—are now recognized as eligible under the International Psoriasis Council’s (IPF’s) updated classification.1 A study of real-world data demonstrated that 12 months of risankizumab treatment led to substantial skin clearance and quality of life improvements in this previously underrepresented group.
A new analysis highlights the effectiveness of risankizumab in patients with moderate plaque psoriasis and those newly classified as systemic therapy eligible. | Image credit: fusssergei – stock.adobe.com
This retrospective study is published in Dermatology and Therapy.
“After 12 months of continuous treatment with risankizumab, all patient groups evaluated in this study showed significant improvements in their PASI [Psoriasis Area Severity Index] scores,” wrote the researchers of the study. “The majority achieved NPF [National Psoriasis Foundation] treat-to-target goals and had significant improvement in quality of life, psoriasis symptoms, and reduced work and activity impairment.”
Although psoriasis treatment guidelines have historically focused on patients with BSA involvement greater than 10%, growing evidence highlights that individuals with BSA of 3% or less can experience a disease burden comparable to those with more extensive skin involvement.2 Data from the CorEvitas Psoriasis Registry show that patient-reported outcomes (PROs) related to itch, pain, fatigue, and quality of life significantly overlap across low, medium, and high BSA categories.
This analysis utilized data from the CorEvitas Psoriasis Registry to evaluate real-world outcomes in biologic-naïve adults with moderate to severe plaque psoriasis who initiated risankizumab treatment between April 2019 and August 2023.1 Eligible patients received continuous risankizumab therapy for 12 months and were stratified by baseline BSA: 3% to 10% or greater than 10%.
Within the BSA 3% to 10% subgroup, patients were further assessed for involvement of high-impact areas and prior use of topical therapy, aligning with the IPF criteria for systemic therapy eligibility. Effectiveness outcomes included achievement of Psoriasis Area and Severity Index (PASI) 90 and 100 and National Psoriasis Foundation (NPF) treat-to-target goals. PROs included the proportion achieving a Dermatology Life Quality Index (DLQI) score of 0/1, as well as changes in symptom burden and work or activity impairment from baseline.
Among the 272 patients included in the analysis, 123 had baseline BSA between 3% and 10%, of whom 78 had psoriasis in high-impact areas and 105 had a history of topical therapy use, meeting IPC criteria for systemic eligibility. The remaining 149 patients had BSA greater than 10%. In the BSA 3% to 10% group, 77.9% achieved PASI 90 and 67.2% achieved PASI 100 after 12 months of risankizumab treatment. Additionally, 95.3% met the NPF’s acceptable target, and 87.9% reached the optimal target.
PROs were similarly encouraging, with 68.1% achieving a DLQI score of 0/1, indicating minimal impact on quality of life. Statistically significant improvements were also observed in psoriasis symptom burden and reductions in both work and activity impairment (P < .001). Furthermore, comparable clinical and quality of life benefits were seen across all IPC-defined subgroups, supporting the effectiveness of risankizumab in patients beyond traditional systemic therapy thresholds.
However, the researchers noted several limitations. Although safety outcomes were not evaluated, prior clinical trials have demonstrated a favorable long-term safety profile for risankizumab. Ongoing studies (EUPAS3935; NCT04799990) aim to assess the real-world safety of risankizumab more comprehensively. Additionally, the current analysis was limited by the absence of head-to-head comparisons with other biologic or systemic therapies in patients newly classified as systemic-eligible under IPC guidelines. The lack of comparable real-world studies for alternative treatments also limited these findings.
Despite these limitations, the researchers believe the study provides evidence that supports risankizumab in patients eligible for systemic therapy under IPC guidelines.
“Given these outcomes, risankizumab may be considered a primary systemic therapy option for treating patients eligible for systemic therapy,” wrote the researchers.
References
1. Strober B, Patel M, Kaldas MI, et al. Real-world skin clearance and quality of life with risankizumab in patients with psoriasis with moderate skin involvement and those eligible for systemic therapy per International Psoriasis Council classification. Dermatol Ther (Heidelb). Published online July 2, 2025. doi:10.1007/s13555-025-01474-3
2. Steinzor P. Low BSA in psoriasis may still mean high disease burden. AJMC®. June 12, 2025. Accessed July 2, 2025. https://www.ajmc.com/view/low-bsa-in-psoriasis-may-still-mean-high-disease-burden
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