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Articles de revues sur le sujet « Sin (deity) »

Auteur : Grafiati

Publié le 25 juillet 2024

Mis à jour le 31 juillet 2025

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1

Myers, C. Mason. "Free Will and the Problem of Evil." Religious Studies 23, no. 2 (1987): 289–94. http://dx.doi.org/10.1017/s0034412500018783.

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Hume after arguing for the compatibility of liberty and necessity, a view now known as soft determinism or compatibilism, noted that it is not ‘possible to explain distinctly, how the Deity can be the mediate cause of the actions of sin and moral turpitude’. It seems that Hume is correct if the explanation must show specifically why an omnipotent and omnibenevolent deity must permit certain actions that to human reason seem to be unnecessary evils. On the other hand if such specifity is not required, the soft determinist who also happens to be a theist can argue that it is possible that the ac

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Mitchell, J. Allan. "Reading God Reading “Man”: Hereditary Sin and the Narrativization of Deity in Paradise Lost , Book 3." Milton Quarterly 35, no. 2 (2001): 72–86. http://dx.doi.org/10.1111/1094-348x.00011.

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Gasparov, Igor. "Evil and Free Will: Contemporary Free-Will Defense and Classical Theism." Philosophy. Journal of the Higher School of Economics IV, no. 4 (2020): 15–34. http://dx.doi.org/10.17323/2587-8719-2020-4-15-34.

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The article considers contemporary free will defences, proposed by A. Plantinga, R. Swinburne, according to which the existence of a world in which there is free will is something more valuable than the existence of a world in which there is no free will. It is shown that contemporary forms of free will defences share with atheistic arguments from evil an anthropomorphic model of God, in which God is thought as an individual among other individuals, although endowed with attributes such as omniscience and omnipotence to an excellent degree. It has also been shown that another important point o

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Bischoff, Andreas M. "Name of thrones?" Altorientalische Forschungen 45, no. 1 (2018): 36–41. http://dx.doi.org/10.1515/aofo-2018-0003.

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AbstractThis article deals with the etymology of the Hattic throne-goddess dḪanwaašuit and the functions of the Hattic case ending with -(V)n. Usually, this case marks a noun for the genitive case in a phrase with two nouns N1-(V)n N2. In the Hattic corpus, there are nouns ending with -(V)n without having a second noun (N2) next to it (free n-case). This paper provides examples of free n-case words with possessive meanings, e. g. takeha=un „the lion’s one“ or wur=un „the country’s (people)“. A free n-case word is a denominal noun which is comparable with a possessive noun or a nominalized adje

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Widya, Dhyana, та C. Dewi Hartati. "The Meaning of The Shen Nong Da Di's (神农大帝Shen Nong Da Di) Birthday Ceremony at Ngo Kok Ong Temple Cibarusah, West Java". Sinolingua: Journal of Chinese Studies 2, № 1 (2024): 30. http://dx.doi.org/10.20961/sinolingua.v2i1.79853.

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<p>This article discusses the meaning of the tradition Shen Nong Da di’s birthday ceremony (sejit) at Ngo Kok Ong Temple, Cibarusah, West Java. Ngo Kok Ong temple put Shennong Dadi in Hokkien dialect is called Sin Long Tay Te which means Agricultural Emperor as the main deity. The research methodology and data collection techniques used are qualitative methods. Data collection by indepth interviews and participant observations. Observations and participant observation carried out during the ceremony of Shen Nong's birthday from 26 June 2019 to 29 June 2019 with a descriptive analysis des

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Nor, Z. М. "A View on Religious Tolerance in Nigeria: A Role of the African Traditional Religion (ATR)." Uchenie zapiski Instituta Afriki RAN 70, no. 1 (2025): 42–55. https://doi.org/10.31132/2412-5717-2025-70-1-42-55.

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Religion is a significant social phenomenon that influences human life, particularly through its claims about physical and spiritual meaning. In Nigeria, three major religions exist: African Traditional Religion (ATR), Christianity, and Islam. While ATR is indigenous, Christianity and Islam are imported and considered revealed religions. Both foreign religions claim divine mandates to convert humankind, asserting their monotheistic God as the only true deity. Christianity’s doctrines are rooted in the Apostle’s Creed, while Islamic beliefs are derived from the Hadith of Prophet Mohammed (AS).

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Ismail, Ahmad Munawar, and Ismail Mohd. "Understanding and Appreciation of the Concept of Shirk according to Mathematical Theory." Islamiyyat 44, no. 1 (2022): 241–52. http://dx.doi.org/10.17576/islamiyyat-2022-4401-21.

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Shirk means associating any partners with Allah SWT. Tawhid clearly teaches us that Allah SWT does not share His Rububiah (Lordship) or divine attributes with anything or any partner. A clear example of shirk is idolatry or polytheism, that is worship of deity, god or anything other than Allah. Shirk is a paramount sin in Islam, the one unforgivable sin. However, this term is in the holy verses of the Qur'an that are "difficult" for humans to understand and appreciate. Usually, the interpretation of the word shirk will be given a description of its meaning and consequences to the perpetrator.

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Sholahudin, Shofwan. "Zahirah al-Du’a al-Musytarak baina al-Mutadayyinin bi Indonesia: Nazrah min Manzur al-Islam." Journal of Comparative Study of Religions 3, no. 02 (2024): 89–111. http://dx.doi.org/10.21111/jcsr.v3i02.10499.

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This article examines the practice of interfaith prayers and Islamic perspective of it. The phenomenon of interfaith prayers in Indonesia is a result of the widespread understanding of religious pluralism propagated by liberals in this country. After a deeper examination using critical analysis, it is found that such prayers cannot be justified and are not acceptable to sound reason and true faith. Each religious community participating in joint prayers has their own diverse concepts of God, and each of them has their distinct ways to depict their deity and specific methods of expressing their

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Lumingkewas, Marthin Steven, Antonius Missa, and Andreas Bayu Krisdiantoro. "GOLDEN CALF NARRATIVE: Deuteronomist Ideology of Jeroboam Reformation." MAHABBAH: Journal of Religion and Education 3, no. 1 (2022): 67–81. http://dx.doi.org/10.47135/mahabbah.v3i1.24.

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Jeroboam 1st is depicted as the prototype for all future evil kings, who are regularly accused According to the books of Kings. Jeroboam accused of established two sanctuaries; Bethel and Dan to rival the temple of Solomon in Jerusalem. These shrines then provoke vehement censure and sin of Jeroboam become paradigmatic of northern apostasy. Underlying the negative depiction of Jeroboam’s cult, however, scholars have found subtle details suggesting that Jeroboam’s cult was traditional and even Yahwistic in nature. His calves may be best understood as familiar Canaanite vehicles for the invisibl

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KEHINDE, TAYE ADETUTU. "SEMIOTICS IN IFÁ CORPUS." College of Languages and Communication Arts Education, Lagos State University of Education 2, no. 1 (2023): 83–90. https://doi.org/10.5281/zenodo.8307052.

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Semiotics is a theory in literature that tends to study and analyze the signs and symbols present in literary corpus of which Ifa is one. It looks at how these signs and symbols convey meaning and interpretation. Semiotics explores the relationship between the signifier (the physical form of the sign) and the signified (the concept or idea represented by the sign). This theory helps us to understand how language, images, and other forms of communication contribute to the overall meaning and interpretation in a literary work. By examining the semiotics, we can uncover deeper layers of meaning,

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Weisberger, A. M. "Depravity, Divine Responsibility and Moral Evil: A Critique of a New Free Will Defence." Religious Studies 31, no. 3 (1995): 375–90. http://dx.doi.org/10.1017/s0034412500023726.

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One of the most vexing problems in the philosophy of religion is the existence of moral evil in light of an omnipotent and wholly good deity. A popular mode of diffusing the argument from evil lies in the appeal to free will. Traditionally it is argued that there is a strong connection, even a necessary one, between the ability to exercise free will and the occurrence of wrong-doing. Transworld depravity, as characterized by Alvin Plantinga, is a concept which has gone far to explain this relationship. Essentially, the notion of transworld depravity involves the claim that in any world where a

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HUANG, Jiaofeng. "The Normal Standards and the Three Standards: Examining the New Situation of Mohist Religious Thought." Asia-Pacific Journal of Humanities and Social Sciences 3, no. 3 (2023): 035–45. http://dx.doi.org/10.53789/j.1653-0465.2023.0303.005.

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The chapter titled “Fa Yi” within the book Mozi delves into the religious doctrines of the Mohist belief in a higher deity, serving as the bedrock of legitimacy for the Mohist religion. In addition, the empirical principle of “San Biao,” found scattered throughout various chapters of Mozi, forms the basis for evaluating the effectiveness and utility of Mohist judgments and arguments, thus contributing to the establishment of Mohist religious thought. However, in the past, the religious significance of “Fa Yi” and “San Biao” has often been overlooked, leading to regrettable omissions. This arti

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Subba, Nawa Raj. "Tungdunge Mundhum Establishes a Link Between the Sen and the Samba Dynasties." IAR Journal of Humanities and Social Science 3, no. 1 (2025): 1–10. https://doi.org/10.5281/zenodo.15072276.

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Abstract:Mundhum is knowledge. Kirat's Mundhum is comparable to the Hindu Vedas. Some even consider it folklore. The culture of Kirat was formed by combining Mundhum's wisdom and philosophy with faith. Tungdunge Mundhum is the story of Kirat Samba's ancestral relationship, empowerment, and travel details. Tungdunge used to be their ancestral deity to be worshipped every three years. Kirat Limbu is an indigenous group living in Eastern Nepal, India, Bhutan, and abroad. Different surnames identify them, and one of them is Samba Phyang. The study attempted to examine facts to connect the epic and

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Drout, Michael D. C., and Caiden Kumar. "Aid from the Elf-Ruler: Line 1314a and the Pre-Christian Antecedents of Beowulf." Studies in Philology 121, no. 2 (2024): 209–35. http://dx.doi.org/10.1353/sip.2024.a923964.

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Abstract: Line 1314b of Beowulf is regularly emended to “alwalda” (Ruler of All) from the manuscript form “alf walda” (Ruler of Elves). But the other instances of “alwalda” in Beowulf do not have visible space between the l and the w , and no plausible motivation for the addition of an f and a space has been proposed if the exemplar read “alwalda.” We contend, therefore, that MS “alf walda” is correct, and that the compound refers to the pre-Christian deity Yngvi-Freyr (to use the more familiar Norse name) rather than to the Christian God. We note that in the same passage in which “alf walda”

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Jordan, Nané. "Goddess Puja in California: Embodying Contemplation Through Women’s Spirituality Education." Contemplative Practice, Education, and Socio-Political Transformation (Part Two) 21, no. 1 (2020): 13–25. http://dx.doi.org/10.7202/1071571ar.

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This essay conveys an embodied, relational view of contemplative practice in education through my experience of a “Goddess puja.” I undertook this puja with two other women in the context of exploring and documenting the experiences of seven faculty and student alumni, myself included, within a Women’s Spirituality Master of Arts (WSMA) degree program located in the San Francisco Bay area. I highlight a holistic, ritual scope for considering “contemplative practices,” by engaging an embodied view of contemplative practice based from Women’s Spirituality education. The practice of Goddess puja

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Orosco Chávez, Ana Cecilia. "Las maravillas de Quelucas: La niña que teje sueños en hilos." Revista Intercultural Manguaré 3, no. 2 (2024): 63–66. http://dx.doi.org/10.55996/manguare.v3i2.248.

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En la región Amazonas, provincia de Chachapoyas, en las altas montañas de la querida Jalca Grande, en el pueblo llamado Quelucas, vive una niña extraordinaria llamada Majherli Araceli Culqui Huaman, nacida el 24 de agosto de 2016. A sus siete añitos, Majherli destaca por su habilidad para tejer en el telar de cintura, un arte que aprendió de su querida madre Deisy Huaman Puerta. La pequeña niña es una alumna ejemplar de la Institución Educativa N° 18260 Quelucas, una escuela conocida por su enfoque innovador y su dedicación a preservar la cultura local. Aquí, Majherli participa con entusiasmo

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Subba, Nawa Raj. "Tungdunge Mundhum Establishes a Link Between the Sen and the Samba Dynasties." IAR Journal of Humanities and Social Science 3, no. 01 (2022): 1–10. http://dx.doi.org/10.47310/iarjhss.2022.v03i01.001.

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Mundhum is knowledge. Kirat's Mundhum is comparable to the Hindu Vedas. Some even consider it folklore. The culture of Kirat was formed by combining Mundhum's wisdom and philosophy with faith. Tungdunge Mundhum is the story of Kirat Samba's ancestral relationship, empowerment, and travel details. Tungdunge used to be their ancestral deity to be worshipped every three years. Kirat Limbu is an indigenous group living in Eastern Nepal, India, Bhutan, and abroad. Different surnames identify them, and one of them is Samba Phyang. The study attempted to examine facts to connect the epic and genealog

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Burley, Mikel. "Reproaching the Divine: Poetic Theologies of Protest as a Resource for Expanding the Philosophy of Religion." Journal of the American Academy of Religion 89, no. 4 (2021): 1229–55. http://dx.doi.org/10.1093/jaarel/lfab101.

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Abstract Engaging with works of poetry is one effective, yet hitherto underdeveloped, means of diversifying the philosophy of religion beyond the standard preoccupations with narrow formulations of theism. This article explores and exemplifies this potential in relation to two major poetic figures, namely R. S. Thomas and Rāmprasād Sen. Despite their locations in very different religious contexts—Anglican Christianity in twentieth-century Wales, in the one case, and Hindu Goddess devotion in eighteenth-century Bengal, in the other—each of these poets voices sentiments that are redolent of a th

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Schaafsma, Polly. "Sandals as Icons: Representations in Ancestral Pueblo Rock Art and Effigies in Stone and Wood." Arts 5, no. 4 (2016): 7. http://dx.doi.org/10.3390/arts5040007.

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Dating the late 1000s to the mid-1200s CE, petroglyphs of sandal images are among others that distinguish ancient Pueblo rock art in the San Juan and Little Colorado River drainages on the Colorado Plateau from Ancestral Pueblo rock art elsewhere across the Southwest. The sandal “track” also has counterparts as effigies in stone and wood often found in ceremonial contexts in Pueblo sites. These representations reflect the sandal styles of the times, both plain in contour and the jog-toed variety, the latter characterized by a projection where the little toe is positioned. These representations

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Чандра, Л. "Deep Sand God." Iskusstvo Evrazii [The Art of Eurasia], no. 3(30) (September 30, 2023): 264–67. http://dx.doi.org/10.46748/arteuras.2023.03.018.

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Статья посвящена иконографии Бога глубоких песков, гневного буддийского божества, защищавшего, согласно легенде, монаха Сюань-цзана в его путешествии по Центральной и Южной Азии. Приводятся изображения и тексты из Китайской Трипитаки, японского иконографического собрания «Дзёбодай сю» (Эйбан, 1094 г.), трактатов «Цзу-Энь чуань», «Сингон-миккё-зуин-сю», «Тан Сань-цзан чи», «Тем-бу-гё-дзо», «Дзузо-сё» (Ёгэн), «Бессон-закки» и «Сёсон-дзузо» (Синкаку), «Сикасё-дзузо» и «Асаба-сё» (Сёдзё), свитка Дайго-дзи, коллекции Какудзена, сведения из других источников. Перевод статьи Локеша Чандры из «Словаря

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Rebecca J. Manring, Rebecca J. Manring. "রূপরামের ধর্মমঙ্গল আখ্যানের অংকিতচিত্র DharmaMaṅgala and Human Rights". BHĀBANAGARA: International Journal of Bengal Studies 19, № 23 (2025): 2315–30. https://doi.org/10.64242/bijbs.v19i23.1.

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This essay explores how DharmaMaṅgala, a seventeenth-century Bengali epic by Rūparām Cakravartī, intersects with contemporary human rights discourse. Centered on the deity Dharma Ṭhākur and his earthly representative Lau Sen, the narrative reflects enduring concerns with justice, dignity, and social inclusion. Though framed as a devotional text, the poem gives voice to marginalized figures—women, lower-caste individuals, and the poor—highlighting their agency and moral strength within a deeply hierarchical society. Rebecca J. Manring examines how characters like Lau Sen’s loyal companion Kalu

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COMPAINS SILVA, Eneko. "Venezuela: el debate sobre la legitimidad constitucional de la convocatoria a la Asamblea Nacional Constituyente realizada por el presidente Nicolás Maduro el 1 de mayo de 2017." RVAP 111, no. 111 (August 30, 2018): 249–69. http://dx.doi.org/10.47623/ivap-rvap.111.2018.07.

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LABURPENA: 2017ko maiatzaren 1ean, herria pairatzen ari zen krisi ekonomiko eta politiko larria ikusita, Venezuelako Bolibartar Errepublikako presidenteak, Nicolás Maduro Morosek, Batzar Nazional Konstituziogilea deitu zuen, Konstituzioaren 347. eta 348. artikuluen babespean. Deialdiak, ordea, eztabaida handia ekarri zuen doktrinaren alorrean, ordura arte defendatu egin baitzuen halako deialdiak herriak baino ezin dituela egin, erreferendum baten bidez. Lan honek helburu du eztabaida juridiko aberats horretan dauden jarrerak aztertzea eta presidenteak egindako deialdiaren konstituzio-zilegitas

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Tummala, Tej, Ashley S. Sevilla Uruchurtu, Nicholas R. Liguori, E. Abbas, Christopher G. Azzoli, and Wafik S. El-Deiry. "Abstract 4550: Synergistic combinations of lurbinectedin with ONC212 in pancreatic cancer." Cancer Research 84, no. 6_Supplement (2024): 4550. http://dx.doi.org/10.1158/1538-7445.am2024-4550.

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Abstract Pancreatic cancer is a devastating disease with a poor five-year survival rate of approximately 12%. Given the poor prognosis of the disease, there is urgent need for novel therapeutic regimens. Lurbinectedin is chemotherapeutic compound that stalls and degrades RNA Polymerase II after binding to guanine-rich sequences in the minor groove of DNA. This stalls transcription machinery and leads to single- and double- stranded breaks in DNA and subsequent apoptosis. Our group recently described lurbinectedin’s potency as both a single agent and combinatorial agent with irinotecan and 5-fl

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Uruchurtu, Ashley Sanchez Sevilla, Tyler Roady, Agenxnie Anderson, and Wafik S. El-Deiry. "Abstract 3191: Chk1/2 inhibition enhances response to lurbinectedin treatment in small cell lung cancer." Cancer Research 84, no. 6_Supplement (2024): 3191. http://dx.doi.org/10.1158/1538-7445.am2024-3191.

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Abstract Small cell lung cancer (SCLC) remains a significant clinical concern, with only a 7% 5 year survival rate; therefore, there remains an unmet need for efficacious treatments. Lurbinectedin was FDA approved in 2019 to treat platinum-resistant SCLC. Preliminary experiments in SCLC cell lines indicated an increase in intracellular pChk1 when treated with lurbinectedin. Based on these data and our understanding of the role of checkpoint kinases in the DNA damage response (DDR), we hypothesize that the activity of Chk1 is indicative of upregulated DDR activity as a result of double stranded

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Tian, Xiaobing, and Wafik S. El-Deiry. "Abstract 3334: Combined treatment with PG3 and Nelfinavir induced synergistic apoptosis though sustained activation of integrated stress response." Cancer Research 84, no. 6_Supplement (2024): 3334. http://dx.doi.org/10.1158/1538-7445.am2024-3334.

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Abstract Integrated stress response (ISR) activation has been linked to many human diseases, including cancer and neurological diseases. The ISR controls protein synthesis and proteostasis. ISR main effector ATF4 transcriptional factor regulates the balance between survival and cell death. Under acute ISR, ATF4 promotes cell adaptation and survival. Sustained ISR leads to ATF4-mediated apoptosis. In many cancers, mutations or overexpression of oncogenes, results in enhanced cell proliferation and increased protein synthesis, which activate the ISR. Therefore, protein translation is reduced to

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Srinivasan, Praveen R., Arielle J. De La Cruz, Maximilian Pinho-Schwermann, et al. "Abstract 672: Small molecule NSC59984 stimulates mitochondria-dependent ferroptosis and overcomes integrated stress response pro-survival signaling in pre-clinical pancreatic and colorectal cancer models." Cancer Research 84, no. 6_Supplement (2024): 672. http://dx.doi.org/10.1158/1538-7445.am2024-672.

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Abstract Pancreatic and colorectal cancer are leading causes of cancer deaths worldwide. Resistance to current therapeutics is a significant challenge in treating these cancers. Ferroptosis, a non-apoptotic iron-dependent form of cell death characterized by overwhelming lipid peroxidation, has emerged as a potential strategy to overcome drug resistance. Our lab previously identified the small-molecule NSC59984 as a p53 pathway restoring compound that induces reactive oxygen species, requires p73, and targets mutant p53 for ubiquitin-mediated proteolysis involving MDM2 and HSP90. In pre-clinica

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Zhao, Shuai, Lanlan Zhou, Shengliang Zhang та Wafik S. El-Deiry. "Abstract 376: Targeting the convergence on HIF-1α of CDK4/6 and MAPK pathway: Implications for enhanced anticancer strategies". Cancer Research 84, № 6_Supplement (2024): 376. http://dx.doi.org/10.1158/1538-7445.am2024-376.

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Abstract Hypoxia-inducible factor 1-alpha (HIF-1α) plays a pivotal role in orchestrating cellular responses to hypoxia, influencing cancer cell survival and progression. Our previous work identified a non-canonical mechanism wherein Smurf2 mediates HIF-1α degradation under CDK4/6 inhibition. Through proteomic analysis, we discovered that serine 451 phosphorylation occurs on HIF-1α but not in palbociclib-treated samples. Point mutations at this site, substituting serine with alanine, resulted in decreased HIF-1α levels and enhanced interaction with Smurf2. Intriguingly, under palbociclib treatm

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Xia, Yutong Linda, Leiqing Zhang, Maryam Ghandali, Maximilian P. Schwermann, and Wafik El-Deiry. "Abstract 5559: The anti-tumor efficacy and immune effects of combining of ceralasertib, an oral ATR kinase inhibitor, with imipridones, in prostate cancer treatment in vitro and in vivo." Cancer Research 84, no. 6_Supplement (2024): 5559. http://dx.doi.org/10.1158/1538-7445.am2024-5559.

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Abstract Prostate cancer is the most common cancer and the second leading cause of cancer death among men in the United States. There is an estimated 10% to 50% of cases progress to metastatic castration resistant prostate cancer (mCRPC) state within 3 years of diagnosis. mCPRC remains lethal despite therapeutic advances. There is approximately 20% of mCRPC patients present somatic DNA damage repair (DDR) gene mutations. Ceralasertib, formerly known as AZD6738, is a potent and selective orally bioavailable inhibitor of the ataxia tenlangiectasia and Rad3-related (ATR) kinase, which is involved

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Ghandali, Maryam, Praveen Srinivasan, Yutong Xia, et al. "Abstract 7591: Tumor Treating Fields (TTFields) show efficacy in Triple-Negative breast cancer (TNBC) cells alone and in combination with PARP inhibitor Talazoparib." Cancer Research 84, no. 6_Supplement (2024): 7591. http://dx.doi.org/10.1158/1538-7445.am2024-7591.

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Abstract Breast cancer is the most common cancer in women worldwide, and the fifth leading cause of cancer-related deaths globally. Triple-negative breast cancer (TNBC), the most aggressive form of breast cancer, is usually treated with surgery, chemotherapy, and radiation. Tumor Treating Fields therapy are FDA-approved for the treatment of glioblastoma (GBM) and malignant pleural mesothelioma (MPM).TT Fields use alternating electric fields to inhibit tumor growth through mitotic disruption, cellular damage, integrated stress response activation, and immune mechanisms and inhibit cell prolifer

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Purcell, Connor, Praveen Srinivasan, Maximilian Pinho-Schwermann, et al. "Abstract 7228: In-vitro efficacy of Dordaviprone/GSK126 combination therapy on castration resistant and neuroendocrine prostate cancer." Cancer Research 84, no. 6_Supplement (2024): 7228. http://dx.doi.org/10.1158/1538-7445.am2024-7228.

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Abstract Neuroendocrine prostate cancer (NEPC) is an aggressive histologic subtype associated with poor prognosis that commonly arises in later stages as a mechanism of treatment resistance. Activation of oncogenic drivers, in combination with epigenetic changes (such as EZH2 overexpression and DNA methylation) further promotes tumor proliferation and expression of downstream neuroendocrine lineage pathways (in part controlled by transcription factors, including SOX2, ASCL1, and BRN2). Importantly, EZH2 inhibitors (EZH2i) can restore AR expression in CRPC (Ku et al., 2017). Imipridones, includ

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Roady, Tyler J., Nolan Stubbs, Josephine Chen, et al. "Abstract 3173: Impact of hypoxia on the integrated stress response activated by imipridones ONC201 and ONC206 in pediatric diffuse midline glioma cells." Cancer Research 84, no. 6_Supplement (2024): 3173. http://dx.doi.org/10.1158/1538-7445.am2024-3173.

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Abstract Diffuse midline gliomas (DMGs) are highly aggressive, high-grade gliomas which typically arise in children and young adults. With currently approved treatments the median survival from time of diagnosis for pediatric DMG is 8-10 months with only 10% of children living to 2 years post diagnosis. Despite being only 15% of the cases it makes up 40% of the pediatric brain cancer deaths making it the leading cause of death for all pediatric glioma cases. Two recent clinical studies, NCT03416530 and NCT03134131, have shown the clinical efficacy of Dordaviprone (ONC201/TIC10) for the treatme

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Srinivasan, Praveen R., Andrew George, Charissa Chou, et al. "Abstract 587: Tumor treating fields induce the integrated stress response, alter the transcriptional signatures of cellular metabolism, and modulate immune-related cytokines dependent and independent of p53." Cancer Research 84, no. 6_Supplement (2024): 587. http://dx.doi.org/10.1158/1538-7445.am2024-587.

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Abstract Tumor treating fields (TTFields) are an FDA-approved therapy for the treatment of glioblastoma and pleural mesothelioma. TTFields employ alternating electric fields delivered by cutaneous transducer arrays to induce cytostatic and cytotoxic effects on solid tumors. Additionally, recent studies suggest that TTFields may enhance anti-tumor immunity. We performed RNA-seq and multiplexed cytokine profiling in HCT116 wild-type and HCT116 p53-/- human colorectal cancer cells to elucidate TTFields’ effects on the transcriptome and secretome. TTFields lead to profound changes in the transcrip

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Zhou, Lanlan, Leiqing Zhang, Jun Zhang, Shengliang Zhang, and Wafik S. El-Deiry. "Abstract 3331: Preclinical combination of ONC206 with radiotherapy and temozolomide in a GBM mouse orthotopic model." Cancer Research 84, no. 6_Supplement (2024): 3331. http://dx.doi.org/10.1158/1538-7445.am2024-3331.

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Abstract Glioblastoma multiforme (GBM) is the most common form of primary malignant brain tumor in adults. It is also the most aggressive and lethal. Standard of care therapy comprises maximal safe surgical resection followed by adjuvant alkylating agent temozolomide (TMZ) and radiotherapy (RT). There have only been five drugs and one device ever approved by the FDA for the treatment of GBM. The five-year survival rate for GBM patients has shown no notable improvement in the last three decades. We previously reported that the first-in-class imipridone small-molecule Dordaviprone (ONC201) decre

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Weiskittel, Taylor, Kelsey Huntington, Leiqing Zhang, et al. "Abstract 6426: Identification of potential immune biomarkers for GSK-3 inhibitor elraglusib (9-ING-41) in patients with relapsed/refractory metastatic cancer." Cancer Research 84, no. 6_Supplement (2024): 6426. http://dx.doi.org/10.1158/1538-7445.am2024-6426.

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Abstract Cytokines mediate strong immunomodulatory effects in cancer. Elraglusib (9-ING-41), an inhibitor of GSK-3, is a potent antitumor and immune-modulatory agent in phase 2 clinical trials for the treatment of various cancers. Here, we examined the immune environment of elraglusib-treated cancer patients by measuring peripheral blood protein levels to explore whether the expression level of cytokines/chemokines/soluble cell receptors/growth factors (CCSG) is correlated with clinical outcome. Using a customized Luminex platform, the expression of forty CCSG hypothesized to be linked to GSK-

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Costeas, Christos P., Connor Purcell, and Wafik S. El-Deiry. "Abstract 2918: Potential for a novel therapeutic target: Effects of lactate & lactylation in expression of key regulatory cancer proteins." Cancer Research 84, no. 6_Supplement (2024): 2918. http://dx.doi.org/10.1158/1538-7445.am2024-2918.

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Abstract The purpose of our study is to investigate the immunologic, metastatic, and gene regulation effects of lactate in the context of cancer in normoxic and hypoxic conditions to identify novel biomarkers and potential therapeutic targets. We aim to modify the in-vitro cancer microenvironment to show how lactate and lactylation can be exploited using existing cancer treatments. While hyperlactatemia is defined as lactate levels between 2 mmol/L and 4 mmol/L (Foucher et al 2023), tumor biopsies have demonstrated extracellular concentrations as high as 40 mM (Pérez-Tomás et al 2020). Through

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Tajiknia, Vida, Praveen Srinivasan, Maximilian PInho-Schwermann, William MacDonald, Connor Purcell, and Wafik El-Deiry. "Abstract 2093: Co-treatment with KRAS G12D inhibitor MRTX1133 plus TTFields against human pancreatic and Colorectal cancer cell lines results in synergistic up-regulation of cleaved PARP in KRAS G12D & unexpectedly in KRAS G12V as well." Cancer Research 84, no. 6_Supplement (2024): 2093. http://dx.doi.org/10.1158/1538-7445.am2024-2093.

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Abstract Background: Both colorectal and pancreatic cancers are major global health issues and among deadliest cancers with great disease burden. The most commonly mutated oncogenic alteration in human cancers is KRAS, which is prevalent in pancreatic malignancies. The KRAS G12D mutation subtype is present in more than 40% of pancreatic ductal adenocarcinoma (PDAC). To this date there is no available targeted therapy options for patients with KRAS subtype mutations. MRTX1133 has been identified as a non-covalent, potent, and selective inhibitor of KRASG12D. This small molecule inhibitor has be

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Zhang, Shengliang, Lanlan Zhou, Leiqing Zhang, et al. "Abstract 5941: Small molecule NSC59984 synergizes with PARP inhibitors in BRCA1 wild type ovarian cancer." Cancer Research 84, no. 6_Supplement (2024): 5941. http://dx.doi.org/10.1158/1538-7445.am2024-5941.

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Abstract PARP inhibitors (PARPi) targeting poly (ADP-ribose) polymerase are the first clinically approved drugs designed to apply synthetic lethality in BRCA1 mutant/deficient cancer. However, the treatment can cause reversion of BRCA mutation which results in drug resistance. To explore new strategies to improve antitumor efficacy of PARPi, we applied PARPi in combination with a small molecule NSC59984 for cancer therapy. NSC59984 is a small molecular targeting mutant p53 degradation and activating p73 via ROS-ERK2-MDM2 pathway. The treatments with radiation or hydrogen peroxide showed that N

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Chen, Josephine, Tyler J. Roady, Lanlan Zhou, and Wafik S. El-Deiry. "Abstract 7226: Synergy between ONC201 and temozolomide on ATF4 integrated stress response in glioblastoma." Cancer Research 84, no. 6_Supplement (2024): 7226. http://dx.doi.org/10.1158/1538-7445.am2024-7226.

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Abstract Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults, with a median survival of 15 months. The standard of care involves surgical resection followed by chemoradiotherapy. Even with the full course of treatment, GBM is uncurable, and patients eventually relapse. Although temozolomide (TMZ) is the first-choice chemotherapeutic for GBM, tumor drug resistance limits the effects of the treatment. There is a growing need for new therapies with enhanced efficacy on GBM tumors. Dordaviprone (ONC201) is a TNF-related apoptosis inducing ligand (TRAIL)-inducing compound

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Carlsen, Lindsey, Maximilian Pinho-Schwermann, Leiqing Zhang, et al. "Abstract 1189: Modulation of the MSS and MSI colorectal cancer immune microenvironment with FOLFOX and FOLFIRI -/+ anti-PD-1 immunotherapy." Cancer Research 84, no. 6_Supplement (2024): 1189. http://dx.doi.org/10.1158/1538-7445.am2024-1189.

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Abstract Metastatic colorectal cancer (mCRC) is a deadly disease with a five-year survival rate of 14%. Most patients receive 5-FU (F) and folinic acid (FOL) combined with oxaliplatin (OX), irinotecan (IRI), or both (OXIRI). Immune checkpoint inhibitors (ICIs) are effective against microsatellite instable (MSI) tumors, but 95% of mCRC tumors are microsatellite stable (MSS) and ICI-resistant. Though the primary targets of 5-FU, irinotecan, and oxaliplatin are well-understood, their effects on the tumor microenvironment (TME) remain incompletely characterized. Chemotherapy-mediated immune stimul

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Louie, Anna D., Rani Chudasama, Sharon Wu, et al. "Abstract PD6-04: Mutational landscape and immune infiltration of breast cancer metastases to gynecologic and other organs." Cancer Research 82, no. 4_Supplement (2022): PD6–04—PD6–04. http://dx.doi.org/10.1158/1538-7445.sabcs21-pd6-04.

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Abstract Introduction: Breast cancer metastases (BCM), which cause most breast cancer (BC)-associated mortality, have increased genetic complexity compared to early-stage disease. However, the contribution of genetic alterations to site of BCM is not well-understood. Different breast cancer subtypes have varying patterns of BCM, e.g., lobular carcinoma more frequently spreads to gynecologic (Gyn) organs and the GI tract, perhaps hinting at selection pressures wherein some organs are hospitable to tumors with certain genetic alterations. Methods: Relationships between BCM site and mutations det

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Holder, Sheldon L., Robert A. Winn, and Wafik S. El-Deiry. "Abstract 1002: The historically black colleges and universities cancer trial consortium: A way forward to diversifying cancer clinical trials." Cancer Research 84, no. 6_Supplement (2024): 1002. http://dx.doi.org/10.1158/1538-7445.am2024-1002.

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Abstract The National Comprehensive Cancer Center Network cancer guidelines state that the best management for a cancer patient is on a clinical trial. However, the demographics of 74 registration trials for oral cancer therapies from 2009 - 2019 show only 2.5% of participating patients were Black. Similarly, of the 3,593 patients enrolled in all registration trials for new cancer drugs approved by the FDA in 2019, only 4% were Black patients. A third analysis showed that between 2008 and 2018, only 3.1% of cancer trial patients were Black. The underrepresentation of Black patients in cancer c

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Strandberg, Jillian, Anna Louie, William MacDonald, et al. "Abstract 710: Post-exposure suppression of radiation pneumonitis suggests non-redundant independent effects of TGF-beta and TRAIL/DR5." Cancer Research 84, no. 6_Supplement (2024): 710. http://dx.doi.org/10.1158/1538-7445.am2024-710.

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Abstract Radiation pneumonitis is one of the most common but challenging toxicities seen in patients that are receiving ionizing radiotherapy for thoracic malignancies. While radiation effectively eliminates cancer cells, the damage it causes to surrounding healthy lung tissue leads to an immune response that can impact treatment regimen and lead to long term fibrotic tissue formation. The mechanism of radiation pneumonitis and the inflammatory response in the lungs is poorly understood. However, it is known that the TRAIL pathway plays an important role in inflammatory and fibrotic response.

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Clark, Jasmine S., Jorge Jimenez-Macias, Philippa Vaughn-Beaucaire, et al. "Abstract 5110: Exploring the effects of Indirubins in pediatric diffuse high grade glioma models." Cancer Research 84, no. 6_Supplement (2024): 5110. http://dx.doi.org/10.1158/1538-7445.am2024-5110.

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Abstract Diffuse midline glioma (DMG) is an invasive pediatric brain tumor which grows in the pons of the brainstem. The current course of treatment is focal radiation however, DMG continues to have a very poor prognosis with a median survival of less than 10 months. A major barrier for chemotherapeutic treatment of DMG is the blood brain barrier (BBB) which tightly controls access of molecules to the brain. This limits the efficacy of drugs to treat brain cancer and other diseases of the central nervous system. Previous studies from the Lawler lab and others have shown that the indirubin deri

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MacDonald, William J., Praveen R. Srinivasan, Maximilian Pinho-Schwermann, et al. "Abstract 5140: ITGB6 as a predictive biomarker for overall prognosis and PD-(L)1 immune checkpoint blockade response in various cancer types." Cancer Research 84, no. 6_Supplement (2024): 5140. http://dx.doi.org/10.1158/1538-7445.am2024-5140.

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Abstract Our previous work studying the effects of integrin αvβ6 knockdown in cancer cells demonstrated αvβ6 as a method of T cell suppression in a co-culture model. ITGB6, the gene encoding the β6 subunit of αvβ6, is a potent prognostic marker across multiple cancer types. As a major activator of latent TGFβ, αvβ6, and consequently, ITGB6, has considerable therapeutic implications due to the immunosuppressive effect that activated TGFβ has on the tumor microenvironment. A Human Protein Atlas search of ITGB6 expression surveyed the upregulation of ITGB6 across cancer types. Cancer ITGB6 expres

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MacDonald, William J., Praveen R. Srinivasan, Maximilian Pinho-Schwermann та ін. "Abstract 6528: Integrin ɑvβ6 upregulation as a mechanism of T-cell evasion in head and neck squamous cell carcinoma". Cancer Research 84, № 6_Supplement (2024): 6528. http://dx.doi.org/10.1158/1538-7445.am2024-6528.

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Abstract Head and neck squamous cell carcinoma (HNSCC) encompasses malignancies of the mucosal epithelium in the oral cavity, pharynx, and larynx. The lack of effective screening strategies and the typically late stage of detection are contributors to a considerable annual death toll of HNSCC. Additionally, the anatomical proximity of the malignancy to delicate structures of the head and neck leads to tremendous treatment-related morbidity. Therefore, there is great interest in developing life-saving therapies and strategies for treatment de-escalation. The immune checkpoint inhibitor pembroli

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Schwermann, Maximilian, Benedito Carneiro, Shaolei Lu, et al. "Abstract 4248: Patient-derived MTAP-deleted bladder cancer organoid model: A unique platform for drug development." Cancer Research 84, no. 6_Supplement (2024): 4248. http://dx.doi.org/10.1158/1538-7445.am2024-4248.

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Abstract Introduction: Approximately 30% of advanced bladder cancer (BCa) tumors exhibit MTAP gene deletion, which has been associated with luminal subtype BCa, poor response to chemotherapy, and shorter progression to metastatic disease (De Souza 2023). MTAP deletion has been proposed as a potential biomarker for response to pemetrexed and an emerging class of PRMT5 and MAT2A inhibitors in development for MTAP-deleted tumors. Here, we describe the first patient-derived 3D model of BCa with MTAP deletion and its translational potential as a drug sensitivity platform. Methods: A patient (pt) wi

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Tian, Xiaobing, Praveen Srinivasan, and Wafik S. El-Deiry. "Abstract 610: ClpP-dependent and -independent activation of HRI kinase by small molecules." Cancer Research 84, no. 6_Supplement (2024): 610. http://dx.doi.org/10.1158/1538-7445.am2024-610.

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Abstract HRI was initially identified as a kinase essential for maintaining heme-globin balance within red blood cells as well as for controlling the ISR in response to oxidative stress. HRI also responds to a broad range of stresses such as osmotic stress, heat shock, proteasome inhibition. The recently discovered unexpected functions of HRI include innate immunity, translational control of immune evasion in cancer by upregulating PD-L1, proteostasis, mitochondrial stress, inhibition of histone H3 lysine 27 (H3K27) demethylase (KDM6A) and iron deficiency. Importantly, recent evaluation of pat

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Ding, Elizabeth C., Maximilian Pinho-Schwermann, Shengliang Zhang, Connor Purcell, and Wafik S. El-Deiry. "Abstract 3036: Sensitivity of ONC201/TIC10 cancer therapeutic on neuroendocrine prostate cancer (NEPC) and neuroendocrine differentiation (NED)." Cancer Research 84, no. 6_Supplement (2024): 3036. http://dx.doi.org/10.1158/1538-7445.am2024-3036.

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Abstract Although androgen deprivation therapy and androgen receptor (AR) blockade are highly effective therapies for metastatic prostate cancer (PCa), most patients develop resistance, leading to castration-resistant prostate cancer (CRPC). A subset of CRPC shows neuroendocrine prostate cancer (NEPC) features, which are associated with poor prognosis and limited therapeutic strategies. NEPC is characterized by oncogenic driver activation and epigenetic changes, partly controlled by transcription factors like BRN2 and SOX2. AR has been shown to suppress BRN2 transcription, which is required fo

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Muquith, Maishara, Magdalena Espinoza, Andrew Elliott, et al. "Abstract 1213: Tissue-specific thresholds and microenvironment correlates of tumor mutation burden associated with immunotherapy benefit and prognosis in microsatellite stable cancers." Cancer Research 84, no. 6_Supplement (2024): 1213. http://dx.doi.org/10.1158/1538-7445.am2024-1213.

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Abstract Background: Immune checkpoint inhibitors (ICIs) targeting anti-PD-1/L1 have expanded the treatment landscape against cancers, but are only effective in a subset of patients across all cancer types. Tumor mutation burden (TMB) is postulated to be a generic determinant of ICI dependent-tumor rejection. Here, we clarify the association between TMB and survival outcomes among microsatellite-stable cancers in a real-world clinicogenomic cohort including 70,698 patients distributed across 27 histologies. Methods: Patients were segregated into mutually exclusive anti-PD-1/L1 (N=14,736, immun

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Lannigan, Alexis J., Jasper Chan, Maximilian Schwermann, et al. "Abstract 4780: TRAIL-inducing imipridone ONC201/TIC10 demonstrates anti-neoplastic effects in colonic adenoma-derived organoids." Cancer Research 84, no. 6_Supplement (2024): 4780. http://dx.doi.org/10.1158/1538-7445.am2024-4780.

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Abstract Background: Colorectal cancer (CRC) is the second leading cause of cancer-related death inthe United States and screening is the most effective method to reduce mortality. Chemoprevention, which aims to prevent CRC through eradication or prevention of precursor colonic adenomas, represents an alternative strategy to address this problem. The imipridone dordaviprone (ONC201) has been shown to induce apoptosis in cancer cells through both upregulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and the integrated stress response. More recently, we have shown that

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