Mechanistic Modeling of Intrathecal Chemotherapy Pharmacokinetics in the Human Central Nervous System
CONCLUSIONS: CNS PBPK modeling, in line with available clinical efficacy data, confirms the therapeutic value of intrathecal chemotherapy with antibody or small molecule drugs for treating neoplastic meningitis and warrants further clinical investigation of intrathecal antibody drugs to treat brain parenchyma tumors. Compared to intraventricular injection, intraventricular 24-h infusion may mitigate neurotoxicity while retaining potential efficacy.PMID:38289997 | DOI:10.1158/1078-0432.CCR-23-3062 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 30, 2024 Category: Cancer & Oncology Authors: Jing Li Andrew Wu Seongho Kim Source Type: research
Multi-omics analysis reveals immune features associated with immunotherapy benefit in squamous cell lung cancer patients from Phase III Lung-MAP S1400I trial
CONCLUSIONS: The frequency, distribution and clustering of immune cells relative to malignant ones can impact ICI efficacy in SqNSCLC patients. High CNV burden may contribute to the cold immune microenvironment. Soluble inflammation/immune-related proteins in the blood have the potential to monitor therapeutic benefit from ICI treatment in SqNSCLC patients.PMID:38277235 | DOI:10.1158/1078-0432.CCR-23-0251 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 26, 2024 Category: Cancer & Oncology Authors: Edwin Roger Parra Jiexin Zhang Dzifa Yawa Duose Edgar Gonzalez-Kozlova Mary W Redman Hong Chen Ganiraju C Manyam Gayatri Kumar Jianhua Zhang Xingzhi Song Rossana Lazcano Mario L Marques-Piubelli Caddie Laberiano-Fernandez Frank Rojas Baili Zhang Len Taing Source Type: research
Development of a [89Zr]Zr-labeled human antibody using a novel phage-displayed human scFv library
CONCLUSIONS: L111 Ab targets lung cancer cells in vitro and in vivo. [89Zr]Zr-DFO-L111 is a human antibody that will be evaluated in the first-in-human study of safety and PET imaging.PMID:38277241 | DOI:10.1158/1078-0432.CCR-23-3647 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 26, 2024 Category: Cancer & Oncology Authors: Abhay K Singh Calvin D Lewis Cristian A W V Boas Philipp Diebolder Prashant N Jethva Aaron Rhee Jong Hee Song Young Ah Goo Shunqiang Li Michael L Nickels Yongjian Liu Buck E Rogers Vaishali Kapoor Dennis E Hallahan Source Type: research
Dual-hit strategy for therapeutic targeting of pancreatic cancer in patient-derived xenograft tumors
CONCLUSION: This dual-hit strategy of SMO and FGFR inhibition provides a clinically-translatable approach to compromise the profound impermeability of PDAC tumors. Furthermore, clinical deployment of DW-MR imaging could fulfill the essential clinical-translational requirement for patient stratification.PMID:38270582 | DOI:10.1158/1078-0432.CCR-23-0131 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 25, 2024 Category: Cancer & Oncology Authors: Tista Roy Chaudhuri Qingxiang Lin Ewa K Stachowiak Spencer R Rosario Joseph A Spernyak Wen Wee Ma Michal K Stachowiak Michelle K Greene Gerard P Quinn Simon S McDade Martin Clynes Christopher J Scott Robert M Straubinger Source Type: research
FDG PET/CT Imaging 1 Week after a Single Dose of Pembrolizumab Predicts Treatment Response in Patients with Advanced Melanoma
CONCLUSIONS: Early FDG PET/CT can identify metabolic changes in melanoma metastases that are potentially predictive of response to pembrolizumab and significantly correlated with PFS.PMID:38263597 | DOI:10.1158/1078-0432.CCR-23-2390 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 24, 2024 Category: Cancer & Oncology Authors: Thomas M Anderson Bryan H Chang Alexander C Huang Xiaowei Xu Daniel Yoon Catherine G Shang Rosemarie Mick Erin Schubert Suzanne McGettigan Kristin Kreider Wei Xu E John Wherry Lynn M Schuchter Ravi K Amaravadi Tara C Mitchell Michael D Farwell Source Type: research
Facts and hopes in immunotherapy strategies targeting antigens derived from KRAS mutations
Clin Cancer Res. 2024 Jan 24. doi: 10.1158/1078-0432.CCR-23-1212. Online ahead of print.ABSTRACTIn this commentary, we advance the notion that mutant KRAS (mKRAS) is an ideal tumor neoantigen that is amenable for targeting by the adaptive immune system. Recent progress highlights key advances on various fronts that validates mKRAS as a molecular target and supports further pursuit as an immunological target. Since mKRAS is an intracellular membrane localized protein and not normally expressed on the cell surface, we surmise that proteasome degradation will generate short peptides that bind to HLA class I (HLA-I) molecules ...
Source: Clinical Cancer Research - January 24, 2024 Category: Cancer & Oncology Authors: Gerald P Linette Adham S Bear Beatriz M Carreno Source Type: research
Germline USP36 mutation confers resistance to EGFR-TKIs by upregulating MLLT3 expression in non-small cell lung cancer patients
CONCLUSION: These findings characterized rs3744797 as an oncogenic variant in mediating EGFR-TKIs resistance and tumor aggressiveness through deubiquitinating MLLT3, highlighting the variant as a predictive biomarker for EGFR-TKIs response in NSCLC.PMID:38261467 | DOI:10.1158/1078-0432.CCR-23-2357 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 23, 2024 Category: Cancer & Oncology Authors: Shaoxing Guan Xi Chen Yuru Wei Fei Wang Wen Xie Youhao Chen Heng Liang Xia Zhu Yunpeng Yang Wenfeng Fang Yan Huang Hongyun Zhao Xiaoxu Zhang Shu Liu Wei Zhuang Min Huang Xueding Wang Li Zhang Source Type: research
From serendipity to intention: development of brain penetrant PARP1 selective inhibitors
Clin Cancer Res. 2024 Jan 22. doi: 10.1158/1078-0432.CCR-23-3571. Online ahead of print.ABSTRACTPrimary and secondary brain tumors cause significant mortality and constitute an important unmet need. The development of AZD9574, a brain-penetrant, PARP1 selective inhibitor, with favorable pharmacologic properties and intriguing preclinical activity, has led to an ongoing clinical trial evaluating it alone and in combination with temozolomide or antibody drug conjugates.PMID:38251977 | DOI:10.1158/1078-0432.CCR-23-3571 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 22, 2024 Category: Cancer & Oncology Authors: Filipa Lynce Nancy U Lin Source Type: research
Unveiling Liquid Gold: Lymph as an HPV Marker in OPSCC to guide treatment decisions
Clin Cancer Res. 2024 Jan 22. doi: 10.1158/1078-0432.CCR-23-3549. Online ahead of print.ABSTRACTDistinguishing low versus high-risk HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) is pivotal for tailoring treatment. Liquid biopsy, measuring cell-free HPV-DNA in serum and saliva, assesses treatment response and early-recurrence risk. Postoperative lymphatic fluid, may better guide future adjuvant therapy decisions due to its proximity to primary lesions and lymph nodes.PMID:38252056 | DOI:10.1158/1078-0432.CCR-23-3549 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 22, 2024 Category: Cancer & Oncology Authors: Nicholas Brian Shannon N Gopalakrishna Iyer Source Type: research
KLRG1 Cell Depletion As A Novel Therapeutic Strategy In Patients With Mature T-cell lymphoma Subtypes
CONCLUSIONS: Our findings suggest the potential benefit of a broader treatment strategy combining therapeutic antibodies with PI3Ki for the treatment of patients with mature T-cell and NK-cell neoplasms.PMID:38252421 | DOI:10.1158/1078-0432.CCR-23-3504 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 22, 2024 Category: Cancer & Oncology Authors: Bimarzhan Assatova Robert Willim Christopher Trevisani Garrett Haskett Khyati Maulik Kariya Kusha Chopra Sung Rye Park Michael Yevgeniy Tolstorukov Sean M McCabe Jessica Duffy Abner Louissaint Jani Huuhtanen Dipabarna Bhattacharya Satu Mustjoki Min Jung K Source Type: research
Clinical and genomic predictors of adverse events in newly diagnosed glioblastoma
CONCLUSION: Genomic biomarkers based on functional variant analysis of a routine clinical panel may help identify adverse events in GBM, particularly seizures. Identifying these risk factors could improve the management of patients through better supportive care and consideration of prophylactic therapies.PMID:38252427 | DOI:10.1158/1078-0432.CCR-23-3018 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 22, 2024 Category: Cancer & Oncology Authors: Mary Jane Lim-Fat J Bryan Iorgulescu Rifaquat Rahman Varun Bhave Alona Muzikansky Eleanor Woodward Sydney Whorral Marie Allen Mehdi Touat Xiaomei Li Gongwen Xu Jay Patel Elizabeth R Gerstner Jayashree Kalpathy-Cramer Gilbert Youssef Ugonma Chukwueke J Ric Source Type: research
Facts and hopes in using omics to advance combined immunotherapy strategies
Clin Cancer Res. 2024 Jan 18. doi: 10.1158/1078-0432.CCR-22-2241. Online ahead of print.ABSTRACTThe field of oncology has been transformed by immune checkpoint inhibitors (ICI) and other immune-based agents, however many patients do not receive a durable benefit. While biomarker assessments from pivotal ICI trials have uncovered certain mechanisms of resistance, results thus far have only scraped the surface. Mechanisms of resistance are as complex as the tumor microenvironment (TME) itself, and the development of effective therapeutic strategies will only be possible by building accurate models of the tumor-immune interfa...
Source: Clinical Cancer Research - January 18, 2024 Category: Cancer & Oncology Authors: Ryan C Augustin Wesley L Cai Jason J Luke Riyue Bao Source Type: research
Phase II DORA Study of Olaparib with or without Durvalumab as a Chemotherapy-Free Maintenance Strategy in Platinum-Pretreated Advanced Triple-Negative Breast Cancer
CONCLUSIONS: PFS was longer than expected with both regimens. A patient subset with wild-type BRCA platinum-sensitive aTNBC had durable disease control with chemotherapy-free maintenance.PMID:38236575 | DOI:10.1158/1078-0432.CCR-23-2513 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 18, 2024 Category: Cancer & Oncology Authors: Tira J Tan Sarah Sammons Young-Hyuck Im Lilin She Kelly Mundy Robert Bigelow Tiffany A Traina Carey Anders Joe Yeong Ezequiel Renzulli Sung-Bae Kim Rebecca Dent Source Type: research
Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft Tissue Sarcomas: Clinical Outcomes and Biological Correlates
CONCLUSIONS: The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.PMID:38236580 | DOI:10.1158/1078-0432.CCR-23-2250 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 18, 2024 Category: Cancer & Oncology Authors: Candace L Haddox Michael J Nathenson Emanuele Mazzola Jia-Ren Lin Joanna Baginska Allison Nau Jason L Weirather Edwin Choy Adrian Marino-Enriquez Jeffrey A Morgan Gregory M Cote Priscilla Merriam Andrew J Wagner Peter K Sorger Sandro Santagata Suzanne Geo Source Type: research
The impact of circulating tumor cell HOXB13 RNA detection in men with metastatic castration-resistant prostate cancer treated with abiraterone or enzalutamide
CONCLUSION: Higher CTC HOXB13 expression is associated with AR-dependent biomarkers in CTCs and is adversely prognostic in the context of potent AR inhibition in men with mCRPC.PMID:38236581 | DOI:10.1158/1078-0432.CCR-23-3017 (Source: Clinical Cancer Research)
Source: Clinical Cancer Research - January 18, 2024 Category: Cancer & Oncology Authors: Susan Halabi Siyuan Guo Joseph J Park David M Nanus Daniel J George Emmanuel S Antonarakis Daniel Costin Danila Russell Zelig Szmulewitz Donald P McDonnell John D Norris Changxue Lu Jun Luo Andrew J Armstrong Source Type: research
