Review
Oncology
Javier Ros, Iosune Baraibar, Emilia Sardo, Nuria Mulet, Francesc Salva, Guillem Argiles, Giulia Martini, Davide Ciardiello, Jose Luis Cuadra, Josep Tabernero, Elena Elez
Summary: The development of therapeutic strategies targeting MAPK/ERK and EGFR signaling in BRAF V600E mutated mCRC, with drugs like encorafenib, binimetinib, and cetuximab, has proven successful in improving clinical outcomes. The BEACON trial using these drugs has established a new standard of care in previously treated BRAF V600E mutant mCRC patients, showing impressive improvement in outcomes and tolerable toxicity compared to chemotherapy.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2021)
Article
Medicine, General & Internal
Gerald W. Prager, Julien Taieb, Marwan Fakih, Fortunato Ciardiello, Eric Van Cutsem, Elena Elez, Felipe M. Cruz, Lucjan Wyrwicz, Daniil Stroyakovskiy, Zsuzsanna Papai, Pierre-Guillaume Poureau, Gabor Liposits, Chiara Cremolini, Igor Bondarenko, Dominik P. Modest, Karim A. Benhadji, Nadia Amellal, Catherine Leger, Loick Vidot, Josep Tabernero
Summary: In this study, researchers found that treatment with trifluridine-tipiracil plus bevacizumab could prolong overall survival in patients with metastatic colorectal cancer compared to trifluridine-tipiracil alone.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
Review
Oncology
Nicola Personeni, Valeria Smiroldo, Emilio Francesco Giunta, Maria Giuseppina Prete, Lorenza Rimassa, Giacomo Bregni, Francesco Sclafani
Summary: Metastatic colorectal cancer (mCRC) poses significant challenges in cancer management, but advancements in precision medicine have led to more personalized treatment strategies. Innovative research on molecular pathways and emerging biomarkers is driving the development of targeted therapies for refractory mCRC, enhancing prognosis and treatment outcomes.
Article
Medicine, General & Internal
Arvind Dasari, Sara Lonardi, Rocio Garcia-Carbonero, Elena Elez, Takayuki Yoshino, Alberto Sobrero, James Yao, Pilar Garcia-Alfonso, Judit Kocsis, Antonio Cubillo Gracian, Andrea Sartore-Bianchi, Taroh Satoh, Violaine Randrian, Jiri Tomasek, Geoff Chong, Andrew Scott Paulson, Toshiki Masuishi, Jeremy Jones, Tibor Csoszi, Chiara Cremolini, Francois Ghiringhelli, Ardaman Shergill, Howard S. Hochster, John Krauss, Ali Bassam, Michel Ducreux, Anneli Elme, Laurence Faugeras, Stefan Kasper, Eric Van Cutsem, Dirk Arnold, Shivani Nanda, Zhao Yang, William R. Schelman, Marek Kania, Josep Tabernero, Cathy Eng
Summary: This study evaluated the efficacy and safety of fruquintinib, a highly selective and potent oral inhibitor of VEGFRs 1, 2, and 3, in patients with advanced, chemotherapy-refractory colorectal cancer. The results showed that fruquintinib significantly prolonged overall survival compared to placebo in patients with refractory metastatic colorectal cancer, with clinical significance. Therefore, fruquintinib could become a global treatment option for patients with refractory metastatic colorectal cancer.
Article
Oncology
Shenshen Wu, Xi Yang, Weiyan Tang, Giuseppe Familiari, Michela Relucenti, Michael Aschner, Xiaobo Li, Rui Chen
Summary: Recent studies have found an association between the PVT1 rs2278176 CT/TT genotypes and a better chemotherapy response, overall survival, and progression-free survival in metastatic colorectal cancer patients. In vivo experiments showed that the rs2278176 C to T mutation inhibited tumor growth and increased apoptosis in colorectal cancer cells treated with 5-Fu. Functional studies revealed that the rs2278176 C to T mutation altered the binding site for hsa-miR-297, leading to downregulation of GSTA2 expression. High GSTA2 expression predicted poor clinical outcomes in metastatic colorectal cancer treated with FOLFOX.
FRONTIERS IN ONCOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Chuntian Huang, Ruijuan Du, Xuechao Jia, Kangdong Liu, Yan Qiao, Qiong Wu, Ning Yao, Lu Yang, Liting Zhou, Xuejiao Liu, Pu Xiang, Mingxia Xin, Yan Wang, Xiaojie Chen, Dong Joon Kim, Zigang Dong, Xiang Li
Summary: The study revealed that CDK15 plays a pivotal role in colorectal cancer progression by phosphorylating PAK4 to promote tumor growth. The CDK15-PAK4 axis may serve as a novel therapeutic target for colorectal cancer.
CELL DEATH AND DIFFERENTIATION
(2022)
Article
Oncology
Donghao Xu, Yu Liu, Wentao Tang, Lingsha Xu, Tianyu Liu, Yudong Jiang, Shizhao Zhou, Xiaorui Qin, Jisheng Li, Jiemin Zhao, Lechi Ye, Wenju Chang, Jianmin Xu
Summary: This study examined the treatment patterns of regorafenib in patients with advanced metastatic colorectal cancer in China. The results showed that both regorafenib monotherapy and combination therapy provided some relief for patients, with regorafenib plus anti-PD-1 antibodies showing better progression-free survival and regorafenib plus chemotherapy yielding the greatest benefit in overall survival. The study also found no significant difference in adverse events among the three groups.
FRONTIERS IN ONCOLOGY
(2022)
Article
Multidisciplinary Sciences
Gonzalo L. Gonzalez-Del Pino, Kunhua Li, Eunyoung Park, Anna M. Schmoker, Byung Hak Ha, Michael J. Eck
Summary: The dysregulation of the RAF/MEK/ERK pathway is associated with many cancers, making the proteins involved, like MEK, a focus of drug discovery efforts. Allosteric MEK inhibitors have complex effects on this pathway and are used in combination with BRAF inhibitors in malignant melanoma. Recent studies suggest that these inhibitors act most potently on BRAF/MEK complexes rather than on free active MEK.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Oncology
Joseph Tintelnot, Inka Ristow, Markus Sauer, Donjete Simnica, Christoph Schultheiss, Rebekka Scholz, Eray Goekkurt, Lisa von Wenserski, Edith Willscher, Lisa Paschold, Sylvie Lorenzen, Jorge Riera-Knorrenschild, Reinhard Depenbusch, Thomas J. Ettrich, Steffen Doerfel, Salah-Eddin Al-Batran, Meinolf Karthaus, Uwe Pelzer, Axel Hinke, Marcus Bauer, Chiara Massa, Barbara Seliger, Claudia Wickenhauser, Carsten Bokemeyer, Susanna Hegewisch-Becker, Mascha Binder, Alexander Stein
Summary: The AVETUX trial combined PD-L1 antibody avelumab with FOLFOX chemotherapy and cetuximab, finding that T cell clonality and diversity may serve as potential markers to predict response to chemo-immunotherapy combinations in MSS mCRC.
FRONTIERS IN ONCOLOGY
(2022)
Review
Oncology
Ambrose H. N. Wong, Brigette Ma, Rashid N. N. Lui
Summary: Colorectal cancer (CRC) is the second most lethal cancer worldwide, and recent advancements in translational research have led to improved treatment outcomes for patients with specific mutations. Understanding resistance mechanisms and the use of ctDNA for therapeutic monitoring have provided new insights for individualized treatment. The feasibility of 'Master Protocols' utilizing ctDNA-based genotyping platforms is being evaluated to broaden the implementation of precision oncology.
THERAPEUTIC ADVANCES IN MEDICAL ONCOLOGY
(2023)
Article
Oncology
Feng Wang, Ming -Ming He, Jian Xiao, Yan-Qiao Zhang, Xiang-Lin Yuan, Wei-Jia Fang, Yan Zhang, Wei Wang, Xiao-Hua Hu, Zhi-Gang Ma, Yi-Chen Yao, Zhi-Xiang Zhuang, Fu-Xiang Zhou, Jie-Er Ying, Ying Yuan, Qing-Feng Zou, Zeng-Qing Guo, Xiang-Yuan Wu, Ying Jin, Zong-Jiong Mai, Zhi-Qiang Wang, Hong Qiu, Ying Guo, Si -Mei Shi, Shuang-Zhen Chen, Hui-Yan Luo, Dong-Sheng Zhang, Feng-Hua Wang, Yu-Hong Li, Rui-Hua Xu
Summary: High-dose vitamin C plus chemotherapy did not show superior progression-free survival compared to chemotherapy alone in patients with metastatic colorectal cancer as first-line treatment, but may be beneficial in patients with mCRC harboring RAS mutation.
CLINICAL CANCER RESEARCH
(2022)
Article
Oncology
R. L. Eefsen, K. S. Simonsen, P. Grundtvig, L. Klarskov, I. M. Chen, D. Hogdall, B. Jensen, T. Lorentzen, T. S. Poulsen, S. Theile, D. Nielsen, E. Hogdall
Summary: In this retrospective analysis, 90% of patients with treatment-refractory mCRC had cancer driver mutations identified through genomic sequencing, but only 2.5% of patients received targeted therapy that matched their mutations. The study highlights the challenge of limited targeted treatment options for mCRC patients with cancer driver mutations.
Article
Oncology
Agnieszka Koper, Slawomir Wilenski, Paulina Sledzinska, Marek Bebyn, Krzysztof Koper
Summary: The study aimed to develop a prognostic model for refractory metastatic colorectal cancer (mCRC) treated with Trifluridine/Tipiracil. Results showed that initial radical treatment, the number of cycles of first-line chemotherapy, the number of cycles of second-line chemotherapy, BRAF mutation, and hypertension were all associated with survival after Trifluridine/Tipiracil initiation. The model and model-based nomogram exhibited an AUC of 0.623 for one-year survival estimation in the testing cohort, with a C-index of 0.632.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Article
Oncology
Sebastian Bauer, James Larkin, F. Stephen Hodi, Frank Stephen, Ellen H. W. Kapiteijn, Gary K. K. Schwartz, Emilano Calvo, Padmaja Yerramilli-Rao, Sophie Piperno-Neumann, Richard D. D. Carvajal
Summary: The combination of PKC inhibitor sotrastaurin and MEK inhibitor binimetinib causes substantial gastrointestinal toxicity in patients with metastatic uveal melanoma, but stable disease is observed in a significant proportion of patients.
FRONTIERS IN ONCOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Shing-Yau Tam, Md Zahirul Islam Khan, Ju-Yu Chen, Jerica Hiu-Yui Yip, Hong-Yiu Yan, Tsz-Yan Tam, Helen Ka-Wai Law
Summary: The study aimed to investigate the differences in chemotherapy responses between FOLFOX-resistant and wild-type colorectal cancer cells using proteomic profiling. FOLFOX-resistant cells (DLD1-R and HCT116-R) were developed through chronic exposure to progressive FOLFOX doses. Analysis of the proteomic profiles revealed significantly altered pathways in FOLFOX-resistant cells, with up-regulations in the ribosomal process and actin cytoskeleton. These findings suggest potential novel treatment targets for overcoming chemoresistance in colorectal cancer.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Health Care Sciences & Services
Vincent Chung, Virginia Sun, Nora Ruel, Thomas J. Smith, Betty R. Ferrell
Summary: This study conducted a secondary analysis on palliative care intervention for pancreatic cancer patients, showing that the intervention may improve patients' QOL and psychological distress. However, a larger phase III trial focusing on pancreatic cancer patients is needed to confirm the effectiveness of the intervention.
JOURNAL OF PALLIATIVE MEDICINE
(2022)
Article
Oncology
Chongkai Wang, Jaideep Sandhu, Marwan Fakih
Summary: Mucinous histology is associated with attenuated response to anti-EGFR therapy in patients with left-sided RAS/BRAF wild-type colorectal cancer. These patients may benefit more from bevacizumab-based therapy. Genomic alterations related to resistance to anti-EGFR therapy were identified in mucinous tumor patients.
Article
Oncology
Marwan Fakih, Huakang Tu, Hil Hsu, Shivani Aggarwal, Emily Chan, Marko Rehn, Victoria Chia, Scott Kopetz
Summary: This article describes clinicopathologic characteristics, treatment patterns, overall survival, and real-world progression-free survival in patients with metastatic colorectal cancer and specific KRAS mutations. The results show that patients with the KRAS p.G12C mutation have poor treatment outcomes and potential prognostic implications.
Article
Oncology
Caroline Even, Jean-Pierre Delord, Katharine A. Price, Kazuhiko Nakagawa, Do-Youn Oh, Matthew Burge, Hyun C. Chung, Toshihiko Doi, Marwan Fakih, Shunji Takahashi, Lili Yao, Fan Jin, Kevin Norwood, Aaron R. Hansen
Summary: In this study, we evaluated pembrolizumab monotherapy for patients with advanced salivary gland carcinoma. The results showed that a subset of patients responded positively to the treatment, with a duration of response exceeding 2 years. The safety profile of pembrolizumab was manageable.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Biotechnology & Applied Microbiology
[Anonymous]
Summary: Identifying mutations in the KRAS gene is crucial for the treatment of colorectal cancer. The introduction of KRAS(G12C) inhibitors has shown safety and efficacy in preclinical studies and early phase trials, although not all tumor types with KRAS(G12C) mutations are responsive to monotherapy. Colorectal cancer patients have shown less benefit, possibly due to treatment-induced resistance through increased EGFR signaling. Combination therapy trials with EGFR inhibitors are currently underway.
ONCOTARGETS AND THERAPY
(2022)
Article
Oncology
Chongkai Wang, Jaideep Sandhu, Amber Tsao, Marwan Fakih
Summary: This study evaluated the impact of coexisting mutations with SMAD4 on overall survival in 433 patients with metastatic colorectal cancer. The results showed that SMAD4 mutations alone were not associated with worse prognosis, but when coexisting with TP53 mutations, they significantly affected patients' overall survival. Patients with concurrent SMAD4 and TP53 mutations represent a distinct poor-prognosis subgroup of metastatic colorectal cancer.
Article
Oncology
Dae Won Kim, Young-Chul Kim, Bence P. Kovari, Vincent Chung, Olatunji B. Alese, Bassel F. El-Rayes, Daneng Li, Wungki Park, Richard D. Kim
Summary: This study suggests that PD-L1 expression on tumor, CD8 T cell infiltration, and the ratio of CD8/regulatory T cells, as well as a six-gene expression profile in the tumor microenvironment, may be potential predictive biomarkers for nivolumab in biliary tract cancers.
EUROPEAN JOURNAL OF CANCER
(2022)
Article
Oncology
Giacomo Mazzoli, Romain Cohen, Sara Lonardi, Francesca Corti, Elena Elez, Marwan Fakih, Priya Jayachandran, Raphael Colle, Aakash Tushar Shah, Massimiliano Salati, Elisabetta Fenocchio, Lisa Salvatore, Margherita Ambrosini, Javier Ros, Rossana Intini, Chiara Cremolini, Michael J. Overman, Thierry Andre, Filippo Pietrantonio
Summary: The evaluation of clinical variables, including performance status (PS), is important in treatment decision-making for patients with dMMR/MSI-H mCRC.
EUROPEAN JOURNAL OF CANCER
(2022)
Review
Oncology
Jason Liu, Percy Lee, Heather M. McGee, Vincent Chung, Laleh Melstrom, Gagandeep Singh, Mustafa Raoof, Arya Amini, Yi-Jen Chen, Terence M. Williams
Summary: This review discusses the recent advances in radiation therapy and neoadjuvant therapy for pancreatic cancer. For locally advanced pancreatic cancer, radiation dose escalation and the use of molecularly targeted agents with radiation have shown promise in improving overall survival. For resectable and borderline resectable pancreatic cancer, ongoing studies are evaluating the effectiveness of multi-drug regimens such as FOLFIRINOX and immune checkpoint inhibitors in improving outcomes.
Article
Oncology
Raphael Colle, Sara Lonardi, Marine Cachanado, Michael J. Overman, Elena Elez, Marwan Fakih, Francesca Corti, Priya Jayachandran, Magali Svrcek, Antoine Dardenne, Baptiste Cervantes, Alex Duval, Romain Cohen, Filippo Pietrantonio, Thierry Andre
Summary: This study evaluated the prognostic value of RAS/BRAF(V600E) mutations and Lynch syndrome on immune checkpoint inhibitor-treated metastatic colorectal cancer patients with microsatellite instability-high/mismatch repair-deficient (MSI/dMMR). The results showed that RAS/BRAF(V600E) mutations were not associated with survival, while Lynch syndrome conferred an improved progression-free survival.
Article
Medicine, General & Internal
Miguel A. Villalona-Calero, Jyoti Malhotra, Vincent Chung, Yan Xing, Stacy W. Gray, Heather Hampel, Stephen Gruber, Kevin McDonnell
Summary: Recent data shows that advanced cancer patients who participate in biomarker/genomically informed early-stage clinical trials benefit clinically. However, most early-stage trials are conducted in academic centers, while the majority of cancer patients in the US are treated in community practices. This article describes efforts at City of Hope Cancer Center to integrate community oncology practices into their academic biomarker/genomic-driven early-stage trial program, aiming to extend the benefits of such trials to community patients. Key initiatives include virtual clinic trials, expansion of clinical trials to regional satellite hubs, and implementation of precision medicine testing programs, which can be used as a model for other institutions.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Biochemical Research Methods
Ye Feng, Erminia Massarelli, Eric Forman, John S. Kovach, Ravi Salgia, Timothy W. Synold
Summary: We have developed and validated a novel LC-MS/MS method for the simultaneous quantification of LB-100 and its active metabolite, endothall, in human plasma following solid-phase extraction. The method exhibited good linearity, precision, and accuracy, enabling accurate measurement of these compounds in patient samples from an ongoing clinical trial (NCT04560972).
Article
Multidisciplinary Sciences
Rena Emond, Jason I. Griffiths, Vince Kornel Grolmusz, Aritro Nath, Jinfeng Chen, Eric F. Medina, Rachel S. Sousa, Timothy Synold, Frederick R. Adler, Andrea H. Bild
Summary: The interplay between drug-sensitive and resistant cells has an impact on the effectiveness of treatment in cancer cell populations. In this study, interaction between estrogen receptor-positive breast cancer cell lineages that are sensitive and resistant to CDK4/6 inhibition was explored. It was found that resistant cells facilitate the growth of sensitive cells through increased metabolism and estradiol production.
NATURE COMMUNICATIONS
(2023)
Article
Health Care Sciences & Services
Afsaneh Barzi, Angela J. Kim, Crystal K. Liang, Howard West, D. Wong, Carol Wright, Nitya Nathwani, Catherine M. Vasko, Vincent Chung, Douglas A. Rubinson, Todd Sachs
Summary: This study identified significant gaps in care delivery for patients with pancreatic adenocarcinoma, particularly in patients with non-metastatic cancer. Deficiencies in germline testing and palliative care were major concerns. Measures should be taken to address these issues in a timely manner.
JOURNAL OF PERSONALIZED MEDICINE
(2023)
Article
Oncology
Jian Ye, Weihua Guo, Chongkai Wang, Colt A. Egelston, Massimo D'Apuzzo, Geereesh Shankar, Marwan G. Fakih, Peter P. Lee
Summary: Our study reveals significant variations in functional status and spatial distribution of immune cells across different metastatic sites in MSS colorectal cancer. These findings suggest that metastatic site-dependent immune contexture may underlie discordant responses to ICI therapy in patients with MSS colorectal cancer.
CANCER RESEARCH COMMUNICATIONS
(2023)