bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the Impact of Biological Agents on Protecting Against Experimental Periodontitis: A Systematic Review of Animal‐Based Studies
Authors: Oliveira Gabriela Ezequiel , da Silva Barbirato Davi , de Menezes Bruna Silva , Fuly Milenna Silva , Pelegrine Henrique Cassebe Ledo , Bonilha Debora Caliendo , de Alencar Julia Gabrielle Pereira , Theodoro Leticia Helena , de Molon Rafael Scaf
Published: December 2024

Aim: This systematic review was aimed at addressing the focused question: What is the protective potential of biological agents against alveolar bone resorption during the progression of experimental periodontitis (EP)?

Material and Methods: The study protocol was registered in the Open Science Framework database (doi:10.17605/OSF.IO/3P2HY). A comprehensive literature search was conducted across PubMed, Web of Science, Cochrane Library, Scopus, and Embase databases up to December 2023. Inclusion criteria consisted of preclinical studies in animal models of EP that examined the effects of biological agents on preventing periodontal bone loss and reducing tissue inflammation. Studies were excluded if they (i) used non‐EP animal models; (ii) focused on antimicrobial agents; (iii) centered on prebiotics or probiotics; (iv) evaluated compounds not classified as biologicals; or (v) included randomized clinical trials, clinical studies, or reviews. Eligibility was determined based on the PI/ECOs framework, and study quality was assessed using the SYRCLE risk‐of‐bias tool.

Results: After screening an initial pool of 5236 records from databases, registries, and hand searches, 39 studies met the inclusion criteria. A total of 23 biological agents were evaluated across these studies. The majority of studies employed the ligature‐induced model of EP to test the effectiveness of biologicals as preventive or therapeutic interventions. The dosage of biological agents and the duration of disease induction varied depending on the EP model. In all studies, the main outcome—alveolar bone loss, a hallmark of EP—was significantly inhibited by biological agents, which also reduced proinflammatory mediators when compared to untreated controls. A key strength of this review is the high number of studies included, most of which were classified as having low risk of bias. However, a notable limitation is the absence of a meta‐analysis, the short follow‐up periods in the included studies, and the heterogeneity among the compound dosages and route of administration.

Conclusion: This systematic review demonstrates that biological agents are effective in reducing bone loss and mitigating inflammation during EP progression. Randomized clinical trials are needed to confirm these findings in human populations.
Response Analysis of Projectile System Under Gaussian Noise Excitation Using Path Integral Method
Authors: Wang Liang , Li Xinyi , Peng Jiahui , Zhang Zhonghua , Dong Shuangqi
Published: December 2024

During flight, projectiles are subject to uncertainties such as aerodynamic forces, wind gusts, and measurement errors; all of which significantly affect their stability and accuracy. As a result, studying the response of projectile systems under stochastic excitation is essential. This paper focuses on the solution and analysis of projectile system responses under stochastic excitation. We employed the path integral method to compute the transient and stationary probability density functions for projectile systems subjected to Gaussian stochastic external and parametric excitations. Based on the probabilistic responses, we analyzed the evolution of the system’s probability density function over time under Gaussian white noise excitation, as well as the changes in the stationary probability density function with air density and flight speed as bifurcation parameters. The analysis results indicate that within a specific range of parameter variations, air density can induce stochastic P‐bifurcation phenomena. Furthermore, increasing air density and flight speed can enhance the stability of the projectile.
Redo Aortic Root Replacement After Prior Modified Inclusion Versus Total Aortic Root Replacement
Authors: Makkinejad Alexander , Wu Xiaoting , Kim Karen , Fukuhara Shinichi , Patel Himanshu , Ailawadi Gorav , Yang Bo
Published: December 2024

Background: There is currently little data in the literature evaluating the long‐term outcomes of reoperative aortic root replacement after previous aortic root replacement, and there are no studies comparing how these outcomes differ based on the approach of the initial aortic root replacement. Our objective was to determine the outcomes of reoperative aortic root replacement following prior aortic root replacement with either the total root or inclusion root techniques.

Methods: This study was a retrospective cohort analysis of 260 patients who underwent redo aortic root replacement from September 1994 to July 2024. Previous root replacements were done with the total root technique in 90 patients and inclusion root technique in 170 patients. The primary outcomes of the study were perioperative complications, operative mortality, and late survival.

Results: The median age of the entire cohort was 57 years, and 79% were males. The prior total root group was younger, had more Marfan syndrome, and more concomitant ascending/arch replacement. Perioperatively, the groups had similar recovery times and complication rates, though there was more postoperative sepsis in the prior total root group (5.6% vs. 0.6%), Operative mortality was 4.2% in the whole cohort; 5.6% in the total root group versus 3.5% in the inclusion root group, p = 0.44. Survival at 5 and 10 years was 84% and 70% in the whole cohort, respectively. The 5‐year survival was similar between the groups at 81% in the total root group and 85% in the inclusion root group, p = 0.82. Cox proportional hazards regression showed infection as a primary indication and was a significant risk factor for late mortality (hazard ratio 2.55 [95% CI: 1.45, 4.50], p = 0.001), as was diabetes (HR: 2.00 [95% CI: 1.04, 3.82], p = 0.037), but previous total root versus inclusion root procedure was not (hazard ratio 1.10 [95% CI: 0.58, 2.09], p = 0.77).

Conclusions: Reoperative aortic root replacement following prior root replacement can be performed with good short‐ and long‐term outcomes after either total root or inclusion root replacement.
Mathematical Modeling and Analysis on the Population Birth Rate Trends in Japan
Authors: Kundu Pulak , Mallick Uzzwal Kumar
Published: December 2024

Japan faces a significant demographic challenge with far‐reaching social, economic, and political ramifications due to its declining birth rate and rapidly rising aging population. Addressing the intricate aspects of these serious emergent phenomena, this study has proposed a mathematical model using a system of ordinary differential equations that has been observed analytically and numerically. As part of the analytical solution, we have verified the model’s existence and uniqueness, investigated its stability at the equilibrium points, and explored its characteristics concerning different state variables. Besides, a sensitivity analysis has been conducted to identify the sensitive parameters based on the estimated parameters. Additionally, the Runge–Kutta fourth‐order approach has been used to find the numerical solutions. This study’s findings have been investigated using a newly proposed mathematical model to highlight the demand for a broad awareness campaign in Japan to address the possible effects of a declining birth rate on social structure and the country’s economy, as well as concerns about rising prices influencing family planning decisions. To sustain population growth in Japan, the government should provide proper initiatives to boost the birth rate.
Supplementary Table 1-16 from Targeting NTRK1 Enhances Immune Checkpoint Inhibitor Efficacy in NTRK1 Wild-Type Non–Small Cell Lung Cancer
Authors: Smith Margaret R. , Dixon Caroline B. , Wang Yuezhu , Liu Yin , D’Agostino Ralph , Ruiz Jimmy , Oliver George , Miller Lance D. , Topaloglu Umit , Chan Michael D. , Farris Michael , Su Jing , Mileham Kathryn F. , Zhao Dawen , Li Wencheng , Sexton Tammy , Lycan Thomas , Haas Karen M. , Grayson Jason M. , Xing Fei
Published: December 2024

Supplementary Table 1-16
Supplementary Data from NUAK1-Mediated Phosphorylation of NADK Mitigates ROS Accumulation to Promote Osimertinib Resistance in Non–Small Cell Lung Carcinoma
Authors: Lin Wei , Wang Na , Wu Shihao , Diao Mingxin , Huang Quanfu , Li Kuo , Mei Peiyuan , Wang Xiaojun , Liao Yongde , Meng Yunchong
Published: December 2024

Supplementary information
Figure S7 from B7-H3–Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity against Solid Tumors
Authors: Jiang Licui , You Fengtao , Wu Hai , Qi Changsong , Xiang Shufen , Zhang Ping , Meng Huimin , Wang Min , Huang Jiequn , Li Yafen , Chen Dan , An Gangli , Yang Nan , Zhang Bozhen , Shen Lin , Yang Lin
Published: December 2024

Supporting data for efficacy comparison of three CART cells in vivo
Figure S5 from B7-H3–Targeted CAR-Vδ1T Cells Exhibit Potent Broad-Spectrum Activity against Solid Tumors
Authors: Jiang Licui , You Fengtao , Wu Hai , Qi Changsong , Xiang Shufen , Zhang Ping , Meng Huimin , Wang Min , Huang Jiequn , Li Yafen , Chen Dan , An Gangli , Yang Nan , Zhang Bozhen , Shen Lin , Yang Lin
Published: December 2024

The efficacy and infiltration of AQ-CAR-IL2-Vδ1T cells in the HCT-15 tumor model
Supplementary figure 5 from Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaw Intawat , Delgado-Calle Jesus
Published: December 2024

Supplementary figure 5
Supplementary Table 1 from Single-Cell Transcriptomic Analysis Identifies Senescent Osteocytes That Trigger Bone Destruction in Breast Cancer Metastasis
Authors: Kaur Japneet , Adhikari Manish , Sabol Hayley M. , Anloague Aric , Khan Sharmin , Kurihara Noriyoshi , Diaz-delCastillo Marta , Andreasen Christina Møller , Barnes Charles Lowry , Stambough Jeffrey B. , Palmieri Michela , Reyes-Castro Olivia , Zarrer Jennifer , Taipaleenmäki Hanna , Ambrogini Elena , Almeida Maria , O’Brien Charles A. , Nookaw Intawat , Delgado-Calle Jesus
Published: December 2024

Supplementary Table 1
Supplementary Data from mLumiOpto Is a Mitochondrial-Targeted Gene Therapy for Treating Cancer
Authors: Chen Kai , Ernst Patrick , Sarkar Anusua , Kim Seulhee , Si Yingnan , Varadkar Tanvi , Ringel Matthew D. , Liu Xiaoguang “Margaret” , Zhou Lufang
Published: December 2024

Supplementary materials and methods, supplementary tables, and supplementary figures
Figure S2-6 from LTβR Agonism Promotes Antitumor Immune Responses via Modulation of the Tumor Microenvironment
Authors: An Disi , Chen Guoying , Cheng Wei-Yi , Mohrs Katja , Adler Christina , Gupta Namita T. , Atwal Gurinder S. , DiLillo David J. , Daly Christopher , Lin John C. , Kuhnert Frank
Published: December 2024

Supplementary Figure S2-6
Data from LTβR Agonism Promotes Antitumor Immune Responses via Modulation of the Tumor Microenvironment
Authors: An Disi , Chen Guoying , Cheng Wei-Yi , Mohrs Katja , Adler Christina , Gupta Namita T. , Atwal Gurinder S. , DiLillo David J. , Daly Christopher , Lin John C. , Kuhnert Frank
Published: December 2024

Abstract
The presence of high endothelial venules (HEV) and tertiary lymphoid structures (TLS) in solid tumors is correlated with favorable prognosis and better responses to immune checkpoint blockade in many cancer types. Elucidation of the molecular mechanisms underlying intratumoral HEV and TLS formation and their contribution to antitumor responses may facilitate the development of improved treatment strategies. Lymphotoxin β receptor (LTβR) signaling is a critical regulator of lymph node organogenesis and can cooperate with antiangiogenic and immune checkpoint blockade treatment to augment tumor-associated HEV formation. In this study, we demonstrated that LTβR signaling modulates the tumor microenvironment via multiple mechanisms to promote antitumor T-cell responses. Systemic activation of the LTβR pathway via agonistic antibody treatment induced tumor-specific HEV formation, upregulated the expression of TLS-related chemokines, and enhanced dendritic cell (DC) and T-cell infiltration and activation in syngeneic tumor models. In vitro studies confirmed direct effects of LTβR agonism on DC activation and maturation and associated DC-mediated T-cell activation. Single-agent LTβR agonist treatment inhibited syngeneic tumor growth in a CD8+ T-cell–dependent and HEV-dependent manner, and the LTβR agonist enhanced antitumor effects of anti-PD-1 and CAR T-cell therapies. An in vivo tumor screen for TLS-inducing cytokines revealed that the combination of LTβR agonism and lymphotoxin ⍺ expression promoted robust intratumoral TLS induction and enhanced tumor responses to anti-CTLA4 treatment. Collectively, this study highlights crucial functions of LTβR signaling in modulating the tumor microenvironment and could inform future HEV/TLS-based strategies for cancer treatments.

Significance: LTβR mediates tumor-specific  high endothelial venule formation and immunomodulation of the tumor microenvironment that promotes antitumor immune responses, supporting LTβR agonism as an approach to enhance the antitumor efficacy of immunotherapies.
Supplementary Table 5 from Cervical Cancer Screening Utilization among Kidney Transplant Recipients, 2001 to 2018
Authors: Hsu Christine D. , Yu Xiaoying , Guo Fangjian , Adekanmbi Victor , Kuo Yong-Fang , Westra Jordan , Berenson Abbey B.
Published: December 2024

Supplementary Table 5 shows the 1-, 2-, and 3-year cumulative incidences of cervical cancer screening by the calendar year of the transplant date.
Supplementary Table 4 from Cervical Cancer Screening Utilization among Kidney Transplant Recipients, 2001 to 2018
Authors: Hsu Christine D. , Yu Xiaoying , Guo Fangjian , Adekanmbi Victor , Kuo Yong-Fang , Westra Jordan , Berenson Abbey B.
Published: December 2024

Supplementary Table 4 shows the sociodemographic and clinical factors associated with cervical cancer screening uptake, using a cause-specific hazard model.
Supplementary Table S5 from Associations of Prostate Tumor Immune Landscape with Vigorous Physical Activity and Prostate Cancer Progression
Authors: Huang Lanshan , Winter Sarah J. , Olsson Linnea T. , Hamilton Alina M. , Halliday Sophia R. , Kirk Erin L. , Farnan Laura , Gerstel Adrian , Craig Stephanie G. , Finn Stephen P. , LaBonte Wilson Melissa , Jain Suneil , Troester Melissa A. , Butler Eboneé N. , Bensen Jeannette T. , Wobker Sara E. , Allott Emma H.
Published: December 2024

Supplementary Table S5. Associations between immune cell types and disease aggressiveness in the pooled study, overall and stratified by ERG expression.
Supplementary Table S3 from Hepatocellular Carcinoma Etiology Drives Survival Outcomes: A Population-Based Analysis
Authors: Cranford Hannah M. , Jones Patricia D. , Wong Robert J. , Liu Qinran , Kobetz Erin N. , Reis Isildinha M. , Koru-Sengul Tulay , Pinheiro Paulo S.
Published: December 2024

3. Supplementary Table S3 shows a multivariable Cox proportional hazards regression model in which HCC-specific survival is assessed based on cigarette smoking status, with the reference population of past smokers.
Table S1 from Plasma Ghrelin and Risks of Sex-Specific, Site-Specific, and Early-Onset Colorectal Cancer: A Mendelian Randomization Analysis
Authors: Hazelwood Emma , Lopez Manzano Catalina , Vincent Emma E. , Albanes Demetrius , Bishop David Timothy , Le Marchand Loïc , Ulrich Cornelia M. , Peters Ulrike , Murphy Gwen , Samadder Niloy Jewel , Anderson Laura , Gunter Marc J. , Murphy Neil , Van Guelpen Bethany , Papadimitriou Nikos
Published: December 2024

SNPs associated with plasma ghrelin
Supplementary Methods S1 from Racial, Ethnic, and Socioeconomic Disparities in Meeting Physical Activity Guidelines among Female Breast Cancer Survivors in the United States
Authors: Wojcik Kaitlyn M. , Wilson Oliver W.A. , Shiels Meredith S. , Sheppard Vanessa B. , Jayasekera Jinani
Published: December 2024

Supplementary Methods S1: NHIS Survey Questions
Supplemental Table 1 from Adiposity throughout Adulthood and Risk of Young-Onset Breast Cancer Tumor Subtypes in the Young Women’s Health History Study
Authors: Marcus Post Lydia , Pathak Dorothy R. , Hamilton Ann S. , Hirko Kelly A. , Houang Richard T. , Guseman Emily H. , Sanfelippo Dan , Bohme Carnegie Nicole , Olson L. Karl , Rui Hallgeir , Schwartz Ann G. , Velie Ellen M.
Published: December 2024

Supplemental Table 1 shows associations between body size throughout adulthood and odds of YOBC subtypes, stratified by household percent poverty (HPP).
Supplementary Table S1 from Cancer Mortality among Hispanic Groups in the United States by Birthplace (2003–2017)
Authors: He Yuelin , Pinheiro Paulo S. , Tripathi Osika , Nguyen Helen , Srinivasan Malathi , Palaniappan Latha P. , Thompson Caroline A.
Published: December 2024

Supplementary Table S1 summarises the denominator population (2005-2017) with sampling errors by Hispanic ethnicity, sex, nativity, and years.
Supplementary Figure S1 from Cancer Mortality among Hispanic Groups in the United States by Birthplace (2003–2017)
Authors: He Yuelin , Pinheiro Paulo S. , Tripathi Osika , Nguyen Helen , Srinivasan Malathi , Palaniappan Latha P. , Thompson Caroline A.
Published: December 2024

Supplementary Figure S1 is a heatmap for Standardized Mortality Ratios comparing mortality rates from specific cancer sites among US-born to foreign- or native- born Hispanic groups, stratified by sex and 5-year group in 2003-2017.
Data from Identification of High-Incidence Populations in the United States for Anti–Epstein-Barr Virus Serologic Screening for Nasopharyngeal Carcinoma
Authors: Clark Payton E. , Taparra Kekoa , Miller Jacob A.
Published: December 2024

AbstractBackground:
In the United States, Epstein-Barr virus (EBV)–associated nasopharyngeal carcinoma (NPC) disproportionately impacts Asian Americans (AA) and Native Hawaiians and other Pacific Islanders (NHPI) who have no access to screening. EBV-based screening trials in Asia have detected most cases at early stages. We sought to identify a US target population for NPC screening and hypothesized that once-lifetime screening could be cost-effective.
Methods:
We obtained NPC incidence data from the Surveillance, Epidemiology, and End Results Asian and Pacific Islander datasets. We estimated the number needed to screen (NNS), mortality reduction, and resource utilization using a validated model and performance data from trials. Six evaluated strategies incorporated serology, nasopharyngeal swab PCR, and endoscopy or MRI.
Results:
Intermediate-incidence and high-incidence populations accounted for 10.7% of US person-years yet 42.7% of cases. Anti-BNLF2b screening with selective endoscopy was the preferred strategy. In high-incidence populations, the median NNS to detect one case was 1,992, with a median of 7.12 NPC deaths averted per 100,000 screened. Screening met the willingness-to-pay threshold in all five high-incidence populations (median incremental cost-effectiveness ratio/gross domestic product, 0.82) and among men in intermediate-incidence populations.
Conclusions:
Nearly half of NPC in the United States arises among the 10% with AA or NHPI ethnicity. A suitable target population for US screening trials would be men and women aged 35 to 65 years of Chinese, Sāmoan, or Southeast Asian ethnicity, or men aged 35 to 60 years of Guamanian/Chamorro, Filipino, or Native Hawaiian ethnicity. Once-lifetime anti-BNLF2b screening could be cost-effective.
Impact:
These data may aid the design of US screening trials. Targeted NPC screening might mitigate health disparities.
Data from The Role of Residential Segregation in Treatment and Outcomes of Ductal Carcinoma In Situ of the Breast
Authors: Nabi Oumarou , Liu Ying , Struthers James , Lian Min
Published: December 2024

AbstractBackground:
It remains unclear whether residential segregation impacts on clinical treatment and outcomes for ductal carcinoma in situ (DCIS), a nonobligate precursor to invasive breast cancer (IBC).
Methods:
This population-based retrospective cohort study included adult non-Hispanic White and Black women diagnosed with unilateral DCIS between January 1990 and December 2015, followed through December 2016, and identified from the Surveillance, Epidemiology, and End Results dataset. County-level racialized economic segregation was measured using the Index of Concentration at the Extremes. Multilevel logistic regression and Cox proportional hazards regression accounting for county-level clustering were used to estimate the ORs of local treatment and HRs of subsequent IBC and mortality.
Results:
Of 103,898 cases, mean age was 59.5 years, 12.5% were non-Hispanic Black, 87.5% were non-Hispanic White, 97.5% underwent surgery, 64.5% received radiotherapy following breast-conserving surgery (BCS), 7.1% developed IBC, and 18.6% died from all causes. Among women living in the least versus most privileged counties, we observed higher odds of receiving mastectomy [vs. BCS; OR = 1.51; 95% confidence interval (CI), 1.35–1.69; Ptrend < 0.001] and radiotherapy following BCS(OR = 1.27; 95% CI, 1.07–1.51; Ptrend < 0.01); the risk was higher in subsequent ipsilateral IBC (HR = 1.16; 95% CI, 1.02–1.32; Ptrend = 0.04), not in breast cancer–specific mortality (HR = 1.04; 95% CI, 0.88–1.23; Ptrend = 0.56).
Conclusions:
The results provide evidence for disparities in clinical treatment for DCIS and prognostic outcomes among women in racially and economically segregated counties.
Impact:
Our findings may inform geographically targeted multilevel interventions to reduce breast cancer burden and improve breast cancer care and equity.
Data from High Incidence of Gastric Cancer in El Salvador: A National Multisectorial Study during 2000 to 2014
Authors: Ruiz de Campos Lisseth , Valdez de Cuellar Marisabel , Norwood Dalton A. , Carrasco Tiffany Y. , Montalvan-Sanchez Eleazar E. , Rodriguez Funes Maria-Virginia , Beasley Timothy , Dominguez Ricardo L. , Bravo Luis E. , Morgan Douglas R.
Published: December 2024

AbstractBackground:
Gastric adenocarcinoma is the fourth leading cause of global cancer mortality and leading infection-associated cancer. Gastric cancer has significant geographic variability, with a high incidence in East Asia and mountainous regions of Latin America. In the United States, gastric cancer represents a marked disparity with incidence rates that are two to three times higher in Hispanics compared to non-Hispanic Whites.
Methods:
We conducted a national retrospective study of incident gastric cancer in El Salvador from to 2000 to 2014 to estimate the age-standardized incidence rate (ASIR) by using a combination of pathology and endoscopy databases. A unique multisectorial coalition was formed between the Ministry of Health (MINSAL) and ES Gastroenterology Society (AGEDES), representing public hospitals (n = 5), governmental employee hospitals (ISSS, n = 5), and private facilities (n = 6), accounting for >95% of national endoscopy capacity. HER2 and EBV tumor status was ascertained in a representative sample during 2014 to 2016.
Results:
A total of 10,039 unique cases of gastric cancer were identified, 45.5% female, and mean age of 65. 21% and 9.4% were <55 and <45 years old, respectively. ASIRs (M, F) were 18.9 (95% CI, 14.4–20.7) and 12.2 per 100,000 persons (95% CI, 10.9–13.5), respectively, in the period 2010 to 2014 with all centers operational. Intestinal gastric cancer was 2.8 times more common than diffuse gastric cancer; 23.2% had partial or complete pyloric obstruction. The HER2 2+/3+ status was 16.7% and EBV-encoded RNA positivity was 10.2%.
Conclusions:
A high incidence of gastric cancer was confirmed in El Salvador and nearly half of the patients were female.
Impact:
The findings have implications for cancer control in the Central America LMICs and for US Latino populations.

See related commentary by Riquelme and Abnet, p. 1550
Data from Cancer Mortality among Hispanic Groups in the United States by Birthplace (2003–2017)
Authors: He Yuelin , Pinheiro Paulo S. , Tripathi Osika , Nguyen Helen , Srinivasan Malathi , Palaniappan Latha P. , Thompson Caroline A.
Published: December 2024

AbstractBackground:
The Hispanic population is the second largest racial/ethnic group in the United States, consisting of multiple distinct ethnicities. Ethnicity-specific variations in cancer mortality may be attributed to countries of birth, so we aimed to understand differences in cancer mortality among disaggregated Hispanics by nativity (native- or foreign-born vs. US-born) over 15 years.
Methods:
A total of 228,197 Hispanic decedents (Mexican, Puerto Rican, Cuban, and Central or South American) with cancer-related deaths from US death certificates (2003–2017) were analyzed. Seven cancers that contribute significantly to Hispanic male (lung and bronchus, colon and rectum, liver, prostate, and pancreas cancers) and female (lung and bronchus, liver, pancreas, colon and rectum, female breast, and ovary cancers) mortality were selected for analysis. 5-year age-adjusted mortality rates [(95% confidence interval); per 100,000] and standardized mortality ratios (95% confidence interval) using foreign-born as the reference group were calculated. Joinpoint regression analysis was used to model cancer-related mortality trends.
Results:
Puerto Rico–born Puerto Ricans, Cuba-born Cubans, and US-born Mexicans had some of the highest cancer death rates among all the Hispanic groups. In general, foreign-born Hispanics had higher cancer mortality rates than US-born Hispanics, except Mexicans. Overall, US-born and non–US-born (i.e., native- or foreign-born) Hispanic groups experienced decreasing rates of cancer deaths over the years.
Conclusions:
We noted vast heterogeneity in mortality rates by nativity across Hispanic groups, a fast-growing diverse US population.
Impact:
Understanding disaggregated patterns and trends in cancer burden can motivate deeper discussion around community health resources, which may improve the health of Hispanics across the United States.
Data from Excess Mortality in Persons with Concurrent HIV and Cancer Diagnoses: A Retrospective Cohort Study
Authors: Lee Kamaria L. , Sarovar Varada , Lam Jennifer O. , Leyden Wendy A. , Alexeeff Stacey E. , Lea Alexandra N. , Hechter Rulin C. , Hu Haihong , Marcus Julia L. , Yuan Qing , Kramer Jennifer R. , Lin Lilie L. , Chiao Elizabeth Y. , Towner William J. , Horberg Michael A. , Silverberg Michael J.
Published: December 2024

AbstractBackground:
With extended lifespans for people with human immunodeficiency virus (PWH), there is a corresponding increased burden of chronic illnesses, including cancer. Our objective was to estimate the excess mortality among PWH with cancer compared with people without HIV (PWoH), accounting for the higher background mortality in the general PWH population.
Methods:
We identified 39,000 PWH and 387,767 demographically matched PWoH in three integrated healthcare systems from 2000 to 2016. We estimated excess mortality among PWH with cancer, computed as the cancer mortality rate difference-in-difference comparing PWH and PWoH. We evaluated five cancer groups: any cancer; virus-, human papillomavirus–, and Epstein–Barr virus –related cancers; virus-unrelated cancers, and common individual cancers. We fitted a multivariable additive Poisson model to estimate excess mortality among PWH with cancer.
Results:
PWH with any cancer had excess mortality compared with PWoH [41.3/1,000 person-years (py), 95% confidence interval (CI), 34.0–48.7]. The highest excess mortality was observed for Epstein–Barr virus–related cancers (63.2/1,000 py, 95% CI, 47.8–78.7), lung cancer (147.7/1,000 py, 95% CI, 41.1–254.3), and non–Hodgkin lymphoma (70.5/1,000 py, 95% CI, 51.4–89.6). Excess mortality among PWH was attenuated from 2009 to 2016, and PWH with cancer had no excess mortality 5 years after diagnosis.
Conclusion:
PWH in care may have excess mortality from certain cancer types, although disparities may have attenuated over time and do not persist beyond 5 years after diagnosis.
Impact:
Findings may guide improved clinical practice and suggest further research is needed to investigate whether cancer treatment or other factors contribute to mortality disparities for PWH with cancer.
The Untapped Opportunities of Addressing Lifecourse Growth in Mammographic Breast Density and Breast Cancer Prevention in Non-Hispanic Black Women
Authors: Pourali Ghazaleh , Toriola Adetunji T.
Published: December 2024

This commentary discusses the importance of adiposity and lifecourse growth with mammographic breast density (MBD) in non-Hispanic Black (NHB) women. Although high MBD is a well-established risk factor for breast cancer, the determinants of MBD in NHB women remain understudied. Although adiposity at the time of mammography is most strongly associated with MBD, adiposity as early as ages 10 and 18 years is also independently associated with MBD. The commentary emphasizes the need for future research to identify biological mechanisms underlying the associations of adulthood adiposity and lifecourse growth with MBD in NHB women and how these can be translated to breast cancer prevention. Additionally, it highlights the need for more studies looking at lifecourse growth and microscopic breast tissue characteristics such as terminal duct lobular unit involution and epithelial-to-stromal proportions.

See related article by Bigham et al., p. 1640
Supplementary Table S3 from Phase II Trial of Gemcitabine and Nab-Paclitaxel for Recurrent Osteosarcoma with Serial Monitoring Using Liquid Biopsy: A Report from the National Pediatric Cancer Foundation
Authors: Dhir Aditi , Hayashi Masanori , Bodlak Avery , Oesterheld Javier , Loeb David M. , Mascarenhas Leo , Isakoff Michael S. , Sandler Eric S. , Borinstein Scott C. , Trucco Matteo , Lagmay Joanne P. , Setty Bhuvana A. , Pratilas Christine A. , Caywood Emi , Metts Jonathan , Yin Hong , Fridley Brooke , Yin Jun , Laborde Jose , Reed Damon R. , Adams Daniel L. , Wagner Lars M.
Published: December 2024

Supplemental Table S3. Detailed ctDNA results over the course of the study.
Figure 5 from Preclinical Evaluation of AZD6422, an Armored Chimeric Antigen Receptor T Cell Targeting CLDN18.2 in Gastric, Pancreatic, and Esophageal Cancers
Authors: Barrett Allison M. , Britton Zachary T. , Carrasco Rosa A. , Breen Shannon , Broggi Maria A.S. , Hatke Amanda L. , Clark Benjamin , Yang Chunning , Phipps Sandrina , Ortiz Lorenzo , Janocha Brianna , Zanvit Peter , Giraldo Nicolas A. , Martin Philip L. , Lapointe Jean-Martin , Harder Nathalie , Cornish Georgina H. , Attili Bala N.N.R. , Mazor Yariv , Damschroder Melissa , Cobbold Mark , Moody Gordon , Bosco Emily E.
Published: December 2024

Optimized manufacturing protocol, STAR-T, for the generation of the CAR-T product. A, Baseline characteristics of donor-matched dnTGFβRII CAR-T cells with traditional manufacture (day 10) vs. AZD6422 (day 4), including CAR+ expression, percent CD4 and CD8 expression, and T-cell phenotypic status as determined by cell surface expression of CCR7 and CD45RO. Results are shown for naïve (CCR7+/CD45RO−, Tn), central memory (CCR7+/CD45RO+, Tcm), effector memory (CCR7−/CD45RO+, Tem), and effector (CCR7−/CD45RO−, Teff) cells. Data are shown as mean ± SEM of representative donors. B, Comparison of bioenergetic profiles of traditionally manufactured dnTGFβRII CAR-T cells vs. AZD6422. Spare respiratory capacity was determined as the differential between basal and maximum respiration. 2-DG, 2-deoxy-D-glucose; ECAR, extracellular acidification rate; FCCP, carbonyl cyanide p-trifluoro-methoxyphenyl hydrazone; OCR, oxygen consumption rate; Oligo, oligomycin; Rot/AA, rotenone and antimycin A. C, Serial restimulation assay to examine cytotoxicity and persistence of dnTGFβRII CAR-T cells and AZD6422. CAR-T cells were co-cultured at a ratio of 1:2 with BXPC3 + CLDN18.2, tumor lysis was measured every 3 to 4 days, and IFNγ was profiled at 24 hours after each new co-culture. Representative of multiple donors. D, Results of quantitative FC to determine cell surface expression of CLDN18.2 across multiple cancer cell lines. Percent cytolysis was determined by xCELLigence RTCA assay after 48 hours of co-culture with AZD6422 at an E:T ratio of 1:1. Data represent mean ± SEM of replicate experiments.
Supplementary Figure S4 from Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma
Authors: Fléchon Aude , Morales-Barrera Rafael , Powles Thomas , Alva Ajjai , Özgüroğlu Mustafa , Csöszi Tibor , Loriot Yohann , Rodriguez-Vida Alejo , Géczi Lajos , Cheng Susanna Y. , Fradet Yves , Oudard Stéphane , Vulsteke Christof , Gunduz Seyda , Mamtani Ronac , Yu Evan Y. , Montesa Pino Alvaro , Anido Urbano , Sendur Mehmet A.N. , Gravis Gwenaelle , Révész János , Kostorov Vladimir , Huillard Olivier , Ma Junshui , Rajasagi Mohini , Vajdi Amir , Lunceford Jared , Cristescu Razvan , Imai Kentaro , Homet Moreno Blanca , Matsubara Nobuaki
Published: December 2024

Supplementary Figure 4. Kaplan-Meier estimates of survival by dual TMB and PD-L1 CPS cutoffs for pembrolizumab plus chemotherapy versus chemotherapy. A, PFS. B, OS.
Supplementary Table 3 from Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects
Authors: Isaacsson Velho Pedro , Bastos Diogo Assed , Saint’ana Pedro Tofani , Rigatti Brenda , da Costa Emily Tonin , Muniz David Q.B. , Andreis Felipe , Ferreira Rafael Dal Ponte , Giongo Pedrotti Luana , Maistro Simone , Katayama Maria Lucia Hirata , Folgueira Maria Aparecida Azevedo Koike , Morelle Alessandra , Leal Alessandro , de Castro Gilberto
Published: December 2024

Supplementary Table 3: Tumor mutational burden and TMB status of patients who performed WES. In grey, a patient with high TMB.
Supplementary Table Names 1 from Characterization of FGFR Alterations and Activation in Patients with High-Risk Non–Muscle-Invasive Bladder Cancer
Authors: Eisner Joel R. , de Jong Florus C. , Shibata Yoichiro , Mayhew Gregory M. , Davison James M. , Carcione Jenna , Pappan Kirk L. , Thomas Shibu , Triantos Spyros , Santiago-Walker Ademi , Baig Mahadi , Milburn Michael V. , Beebe Kirk D. , Zuiverloon Tahlita C.M.
Published: December 2024

Table names for supplementary tables
Supplementary Table Legend 1 from Characterization of FGFR Alterations and Activation in Patients with High-Risk Non–Muscle-Invasive Bladder Cancer
Authors: Eisner Joel R. , de Jong Florus C. , Shibata Yoichiro , Mayhew Gregory M. , Davison James M. , Carcione Jenna , Pappan Kirk L. , Thomas Shibu , Triantos Spyros , Santiago-Walker Ademi , Baig Mahadi , Milburn Michael V. , Beebe Kirk D. , Zuiverloon Tahlita C.M.
Published: December 2024

Supplementary Table Legend
Figure S5 from Characterization of FGFR Alterations and Activation in Patients with High-Risk Non–Muscle-Invasive Bladder Cancer
Authors: Eisner Joel R. , de Jong Florus C. , Shibata Yoichiro , Mayhew Gregory M. , Davison James M. , Carcione Jenna , Pappan Kirk L. , Thomas Shibu , Triantos Spyros , Santiago-Walker Ademi , Baig Mahadi , Milburn Michael V. , Beebe Kirk D. , Zuiverloon Tahlita C.M.
Published: December 2024

Figure S5
Supplementary Figure 1 from Nivolumab in Patients with Metastatic Castration-Resistant Prostate Cancer with and without DNA Repair Defects
Authors: Isaacsson Velho Pedro , Bastos Diogo Assed , Saint’ana Pedro Tofani , Rigatti Brenda , da Costa Emily Tonin , Muniz David Q.B. , Andreis Felipe , Ferreira Rafael Dal Ponte , Giongo Pedrotti Luana , Maistro Simone , Katayama Maria Lucia Hirata , Folgueira Maria Aparecida Azevedo Koike , Morelle Alessandra , Leal Alessandro , de Castro Gilberto
Published: December 2024

Supplementary Figure 1: Consort Diagram for Genomic Analysis
Table S1 from A Preoperative Window-of-Opportunity Study of Oral SERD, Imlunestrant, in Newly Diagnosed ER-Positive, HER2-Negative Early Breast Cancer: Results from the EMBER-2 Study
Authors: Neven Patrick , Stahl Nicole , Vidal Maria , Martín Miguel , Kaufman Peter A. , Harbeck Nadia , Hunt Kelly K. , Carter Stacey , Bidard Francois-Clement , Fasching Peter A. , Aftimos Philippe , Wheatley Duncan , Hamilton Erika , Aft Rebecca , Kulkarni Swati , Schmid Peter , Bhave Manali , Ismail-Khan Roohi , Karacsonyi Claudia , Estrem Shawn T. , Nguyen Bastien , Ozbek Umut , Yuen Eunice , Rodrik-Outmezguine Vanessa , Ciruelos Eva
Published: December 2024

Table depicting the study population
Supplementary Figure S6 from Combinations of HDAC Inhibitor and PPAR Agonist Induce Ferroptosis of Leukemic Stem Cell–like Cells in Acute Myeloid Leukemia
Authors: Zhou Hui , Qin Dongmei , Xie Chendi , Zhou Jie , Jia Shuman , Zhou Ziwei , Qiu Yi , Xu Bing , Zha Jie
Published: December 2024

Supplementary Figure S6. (A-D) Histone deacetylase activity analysis of HDAC1 (A), HDAC2 (B), HDAC3 (C), and HDAC10 (D) in KG-1α and Kasumi-1 cells after treatments with CS055 (4 μM) and chiglitazar (16 μM) by HDAC Activity Assay kit. (E) Quantitative real-time PCR analysis of SLC7A11 mRNA levels in KG-1α and Kasumi-1 cells treated with CS055 and/or chiglitazar for 24 h. (F) Western blotting analysis of HDAC3 expression in KG-1α and Kasumi-1 cells treated with CS055 and/or chiglitazar for 24 h. (G) Western blotting analysis of HDAC3 expression in HDAC3 knockdown KG-1α and Kasumi-1 cells. (H) Western blotting analysis of HDAC3 expression in HDAC3, and HDAC3 mutant (H134A and H135A) overexpressed KG-1α and Kasumi-1 cells. Western blotting data was quantified and analyzed by Image J Soft. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001.
Supplementary Figure S5 from Determination of MYD88 and CXCR4 Mutations for Clinical Detection and Their Significance in Waldenström Macroglobulinemia
Authors: Yan Yuting , Yu Ying , Xiong Wenjie , Wang Jun , Yao Yao , Jia Yujiao , Huang Yanshan , Li Yuxi , Wang Tingyu , Lyu Rui , Sun Hao , Wang Haoxu , Wang Qi , Liu Wei , An Gang , Sui Weiwei , Xu Yan , Huang Wenyang , Yu Zhen , Zou Dehui , Hao Mu , Xiao Zhijian , Wang Jianxiang , Qiu Lugui , Yi Shuhua
Published: December 2024

Supplementary Figure 5. The IGHV-D-J gene repertoire between CXCR4 mutated and wild type groups. (A) Distribution of major VH family gene segments; (B) Distribution of major DH family gene segments; (C) Distribution of major JH family gene segments; (D) Distribution of CDR3 length; (E) Distribution of patients with different identity to germline IGHV gene. *P < 0.05, **P < 0.01.
Supplementary Figure 3 from Multidimensional Immunotyping of Human NF1-Associated Peripheral Nerve Sheath Tumors Uncovers Tumor-Associated Macrophages as Key Drivers of Immune Evasion in the Tumor Microenvironment
Authors: Zhang Lindy , Maalouf Alexandre , Makri Stavriani C. , Banerjee Jineta , Suru Aditya , Tam Ada J. , Calizo Ana , Pollard Kai , Wang Jiawan , Danilova Ludmila , Ioannou Maria , Levin Adam S. , Morris Carol D. , Rhee Daniel S. , Belzberg Allan J. , Blakeley Jaishri O. , Ladle Brian H. , Pardoll Drew M. , Lucas Calixto-Hope G. , Rodriguez Fausto J. , Gross John M. , Anders Robert A. , Pratilas Christine A. , Llosa Nicolas J.
Published: December 2024

Supplementary Figure 3
Table S6. Other c-MET-inhibitors6 from Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non–Small Cell Lung Cancer—Results from the Drug Rediscovery Protocol
Authors: Verkerk Karlijn , van der Wel Tijmen J.W.T. , Zeverijn Laurien J. , Geurts Birgit S. , Spiekman Ilse A.C. , de Wit Gijs F. , Roepman Paul , Jansen Anne M.L. , van der Noort Vincent , Smit Egbert F. , Hoeben Ann , Hendriks Lizza E.L. , van den Heuvel Michel M. , Piet Berber , Herder Gerarda J.M. , Hashemi Sayed M.S. , Gelderblom Hans , Verheul Henk M.W. , Voest Emile E. , de Langen Adrianus J.
Published: December 2024

Study characteristics and efficacy outcomes of trials with selective type 1b c-MET-inhibitors in MET mutated NSCLC. Abbreviations: ECOG, Eastern Cooperative Oncology Group; ORR, objective response rate; CI, confidence interval; mDoR, median duration of response; mPFS, median progression free survival; mOS, median overall survival; METex14, MET exon 14 skipping mutations; NA, not available.
Table S5. Other crizotinib trials5 from Safety, Efficacy, and Biomarker Analysis of Crizotinib in MET-Mutated Non–Small Cell Lung Cancer—Results from the Drug Rediscovery Protocol
Authors: Verkerk Karlijn , van der Wel Tijmen J.W.T. , Zeverijn Laurien J. , Geurts Birgit S. , Spiekman Ilse A.C. , de Wit Gijs F. , Roepman Paul , Jansen Anne M.L. , van der Noort Vincent , Smit Egbert F. , Hoeben Ann , Hendriks Lizza E.L. , van den Heuvel Michel M. , Piet Berber , Herder Gerarda J.M. , Hashemi Sayed M.S. , Gelderblom Hans , Verheul Henk M.W. , Voest Emile E. , de Langen Adrianus J.
Published: December 2024

Study characteristics and efficacy outcomes of trials with crizotinib in MET mutated NSCLC. Abbreviations: ECOG, Eastern Cooperative Oncology Group; ORR, objective response rate; CI, confidence interval; mDoR, median duration of response; mPFS, median progression free survival; mOS, median overall survival; METex14, MET exon 14 skipping mutations; METamp, MET amplification; METmut, METmutation; NA, not available.
Data from Phase II Trial of Gemcitabine and Nab-Paclitaxel for Recurrent Osteosarcoma with Serial Monitoring Using Liquid Biopsy: A Report from the National Pediatric Cancer Foundation
Authors: Dhir Aditi , Hayashi Masanori , Bodlak Avery , Oesterheld Javier , Loeb David M. , Mascarenhas Leo , Isakoff Michael S. , Sandler Eric S. , Borinstein Scott C. , Trucco Matteo , Lagmay Joanne P. , Setty Bhuvana A. , Pratilas Christine A. , Caywood Emi , Metts Jonathan , Yin Hong , Fridley Brooke , Yin Jun , Laborde Jose , Reed Damon R. , Adams Daniel L. , Wagner Lars M.
Published: December 2024

AbstractPurpose:
The combination of gemcitabine and docetaxel is often used to treat patients with recurrent osteosarcoma. Nab-paclitaxel has preclinical activity against osteosarcoma and is potentially less myelosuppressive than docetaxel. We conducted a prospective multi-institutional phase II trial combining gemcitabine and nab-paclitaxel for patients aged 12 to 30 years with recurrent osteosarcoma and measurable disease.
Patients and Methods:
A Simon’s two-stage design was used to test a 4-month progression-free survival (PFS-4) of 10% vs. 35%. Patients received nab-paclitaxel 125 mg/m2 and gemcitabine 1,000 mg/m2 weekly × 3 in 4-week cycles. Immunohistochemical analysis of archival tissue and serial assessment of circulating tumor cells (CTC) and circulating tumor DNA (ctDNA) using ultralow passage whole-genome sequencing were performed to identify potential biomarkers of response.
Results:
Eighteen patients received 56 total cycles (median 2, range 1–12). Two patients (11%) experienced confirmed partial response and six (33%) received >2 cycles. The PFS-4 was 28% (95% confidence interval, 13%–59%). Six patients required dose reductions and three patients were removed due to toxicities. All 18 patients had detectable CTCs and 10 had ctDNA identified. All eight patients with MYC amplification at study entry experienced disease progression.
Conclusions:
Gemcitabine and nab-paclitaxel demonstrated similar clinical activity and toxicity compared to previous retrospective reports utilizing gemcitabine and docetaxel in patients with recurrent osteosarcoma. Serial analysis of CTC and ctDNA was feasible in this prospective multi-institution study and provides preliminary data on the use of these assays in patients with relapsed disease.
Data from Reduced Platelet Activation in Triple-Negative Essential Thrombocythemia Compared with JAK2V617F-Mutated Essential Thrombocythemia
Authors: Dong Huan , Chen Jia , Zhang Jing , Xue Feng , Li Huiyuan , Zhang Donglei , Zhou Hu , Zhang Xian , Huang Yueting , Liu Xiaofan , Chen Yunfei , Liu Wei , Chi Ying , Wang Wentian , Sun Ting , Ju Mankai , Dai Xinyue , Gu Wenjing , Yang Renchi , Fu Rongfeng , Zhang Lei
Published: December 2024

AbstractPurpose:
Triple-negative (TN) essential thrombocytopenia (ET) is characterized by the absence of driver mutations while retaining histologic and phenotypic characteristics sufficient for an ET diagnosis. Our understanding of TN-ET and its platelet activation remains incomplete. We carried out a large-scale multicenter clinical analysis to analyze the clinical and molecular characteristics and thrombotic complications of TN-ET. We also related the above characteristics to platelet activation to further explore the thrombosis mechanism of TN-ET.
Experimental Design:
A retrospective multicenter study was conducted on 138 patients with TN-ET and 759 patients with ET with driver mutations from March 1, 2012 to December 1, 2021. The clinical and molecular characteristics of the patients with TN-ET were summarized. Additionally, platelet activation, apoptosis, and reactive oxygen species (ROS) levels were analyzed in 73 patients with TN-ET from this cohort and compared with 41 age- and sex-matched healthy donors.
Results:
Compared with patients with the JAK2V617F mutation, those with TN mutation were younger (P < 0.001) and exhibited fewer thrombotic events before diagnosis (P < 0.001) and during follow-up (P = 0.039). Patients with TN mutation also presented with significantly reduced CD62P expression in platelets (P = 0.031), slightly reduced calcium concentration in platelets (P = 0.063), increased mitochondrial membrane potential (P = 0.011), reduced phosphatidylserine exposure (P = 0.015), reduced levels of ROS (P = 0.043) and MitoSOX in platelets (P = 0.047).
Conclusions:
In comparison with JAK2V617F-mutated ET, TN-ET is associated with lower platelet ROS levels, which leads to reduced platelet activation and consequently a lower risk of thrombosis.
Data from Synthetic Lethal Targeting of CDK12-Deficient Prostate Cancer with PARP Inhibitors
Authors: Chou Jonathan , Robinson Troy M. , Egusa Emily A. , Lodha Roshan , Zhang Meng , Badura Michelle , Mikayelyan Mane , Delavan Henry M. , Swinderman Jason , Wilson Chris , Zhu Jun , Das Rajdeep , Nguyen Minh , Loehr Andrea , Golsorkhi Tony , Simmons Andrew , Abida Wassim , Chinnaiyan Arul M. , Arkin Michelle R. , Small Eric J. , Quigley David A. , Yang Lixing , Kim Minkyu , Ashworth Alan , Feng Felix Y.
Published: December 2024

AbstractPurpose:
The cyclin-dependent kinase (CDK), CDK12, is mutated or amplified in multiple cancers. We previously described a subtype of prostate cancer characterized predominantly by frameshift, loss-of-function mutations in CDK12. This subtype exhibits aggressive clinical features.
Experimental Design:
Using isogenic prostate cancer models generated by CRISPR/Cas9-mediated inactivation of CDK12, we conducted a chemical library screen of ∼1,800 FDA-approved drugs. We inhibited cyclin K and CDK13 and evaluated the effects on PARP inhibitor (PARPi) sensitivity. CDK12 truncation and kinase domain mutations were expressed in cell lines to determine the effects on PARPi sensitivity. Mice bearing control and CDK12-mutant prostate tumors were treated with rucaparib. Finally, we evaluated PSA responses in patients with CDK12 mutations treated with rucaparib on the TRITON2 trial.
Results:
Cancer cells lacking CDK12 are more sensitive to PARPi than isogenic wild-type cells, and sensitivity depends on the degree of CDK12 inhibition. Inhibiting cyclin K, but not CDK13, also led to PARPi sensitivity and suppressed homologous recombination. CDK12 truncation mutants remained sensitive to PARPi, whereas kinase domain mutants exhibited intermediate sensitivity. The PARPi rucaparib suppressed tumor growth in mice bearing CDK12-mutated tumors. Finally, 6 of 11 (55%) patients with prostate cancer with biallelic CDK12 mutations had reductions in serum PSA levels when treated with rucaparib on the TRITON2 clinical trial.
Conclusions:
In prostate cancer, sensitivity to PARPi is dependent on the specific type and zygosity of the CDK12 mutation. PARPi monotherapy may have some activity in patients with prostate cancer with biallelic inactivating CDK12 alterations.