Review
Biochemistry & Molecular Biology
Mahruba Sultana Niloy, Md Salman Shakil, Md Meharab Hassan Alif, Rhonda J. Rosengren
Summary: Approximately 85% of lung cancer cases are classified as non-small cell lung cancer (NSCLC), with KRAS mutations frequently occurring and leading to decreased overall survival. Plant-based compounds show promise in targeting KRAS-mutated NSCLC cells, inhibiting signaling pathways and offering a wider therapeutic index compared to traditional chemotherapeutic drugs. Further research is needed to explore the potential benefits of natural compounds in treating KRAS-mutant NSCLC.
CURRENT MEDICINAL CHEMISTRY
(2021)
Article
Oncology
Luiz Henrique Araujo, Bianca Mendes Souza, Laura Rabelo Leite, Sabrina A. F. Parma, Natalia P. Lopes, Frederico S. V. Malta, Maira C. M. Freire
Summary: KRAS G12C mutation frequency is higher than other driver mutations in colorectal and non-small cell lung cancer, suggesting KRAS testing should be considered for all patients regardless of clinical or demographic characteristics.
Review
Oncology
Elena Corral de la Fuente, Maria Eugenia Olmedo Garcia, Ana Gomez Rueda, Yolanda Lage, Pilar Garrido
Summary: KRAS is the most frequently altered oncogene in NSCLC, and its mutant tumors have distinct biology and response to treatment, which makes developing effective drugs challenging. The recent discovery of a new pocket in KRAS G12C has led to the development of inhibitors as a new treatment option. However, resistance to targeted KRAS G12C inhibitors is also a concern, and research is ongoing to understand the mechanisms and find suitable drugs. Co-mutations and combination therapy are also areas of interest.
FRONTIERS IN ONCOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Serena Ceddia, Lorenza Landi, Federico Cappuzzo
Summary: This review analyzes the latest research progress on KRAS mutations in non-small-cell lung cancer, describes the biological structure of KRAS, and explores its clinical relevance as a prognostic and predictive biomarker. In addition, this article reviews different treatment approaches for KRAS-mutant lung cancers, with a focus on novel therapeutic strategies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Cheng-Yao Chiang, Songqing Fan, Hongmei Zheng, Wenjun Guo, Zehan Zheng, Yihua Sun, Chuanqi Zhong, Juan Zeng, Shuaihu Li, Min Zhang, Tian Xiao, Duo Zheng
Summary: This study reveals the tumor-suppressive role of SETD7 in non-small cell lung cancer (NSCLC) by modulating KRAS methylation and degradation. SETD7 interacts with KRAS and methylates KRAS at lysines 182 and 184, leading to KRAS degradation and attenuation of the RAS/MEK/ERK signaling cascade.
Review
Oncology
Noriaki Sunaga, Yosuke Miura, Norimitsu Kasahara, Reiko Sakurai
Summary: The v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS) is the most common driver in non-small-cell lung cancer (NSCLC), making targeting KRAS crucial for treatment. While the discovery of covalent KRAS G12C inhibitors offers hope for improving NSCLC patient prognosis, developing combination therapies tailored to tumor characteristics is still necessary given the vast heterogeneity of KRAS-mutated NSCLC.
Article
Multidisciplinary Sciences
Xiaowen Wang, Hong Zhang, Russell Sapio, Jun Yang, Justin Wong, Xin Zhang, Jessie Y. Guo, Sharon Pine, Holly Van Remmen, Hong Li, Eileen White, Chen Liu, Megerditch Kiledjian, Dimitri G. Pestov, X. F. Steven Zheng
Summary: The study reveals a crucial role of nuclear SOD1 in ribosome biogenesis and proliferation in KRAS-driven lung cancer.
NATURE COMMUNICATIONS
(2021)
Review
Oncology
Eabha O'Sullivan, Anna Keogh, Brian Henderson, Stephen P. Finn, Steven G. Gray, Kathy Gately
Summary: KRAS plays a crucial role in regulating cell growth and survival, and its activation is commonly observed in various types of tumors. Recent discoveries have identified a specific pocket in the structure of KRAS, leading to the development of inhibitors that target the G12C mutation. These inhibitors, such as sotorasib and adagrasib, have been approved for the treatment of non-small-cell lung cancer, but their efficacy may be limited by resistance mechanisms in cancer cells.
Article
Oncology
Sam E. Wing, Marta M. Jankowska, Xiaoke Zou, Ernesto Sosa, Jiue-An Yang, Tarik Benmarhnia, Susan L. Neuhausen, Rebecca Nelson, Ravi Salgia, Stacy W. Gray, Loretta Erhunmwunsee
Summary: The purpose of this study was to investigate the relationship between neighborhood disadvantage and somatic KRAS mutations in non-small cell lung cancer (NSCLC) patients. The study found that socioeconomic disadvantage at the neighborhood level was associated with a higher risk of KRAS mutation, while disadvantage related to the built environmental structural measures was inversely associated. These findings suggest that neighborhood disadvantage may contribute to aggressive NSCLC biology through socioeconomic-related stress.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2023)
Review
Cell Biology
Jason Hongting Leung, Benjamin Ng, Wei-Wen Lim
Summary: This article reviews the role of interleukin-11 (IL11) as a potential biomarker in non-small cell lung cancer (NSCLC). It identifies the need for biomarkers in NSCLC and summarizes the available information. Accumulating evidence suggests IL11 to be a potential biomarker in NSCLC patients, but further research is needed.
Article
Medicine, Research & Experimental
Jiawei Guo, Yanan Liu, Jing Lv, Bin Zou, Zhi Chen, Kun Li, Juanjuan Feng, Zhenyu Cai, Lai Wei, Mingyao Liu, Xiufeng Pang
Summary: The research reveals that in KRAS-mutant cancers, BCL6 is upregulated after BET inhibition, and maintained by BRD3 to activate the mTOR signaling pathway. Pharmacological inhibition of BCL6 or mTOR can enhance tumor response to BETi.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Cell Biology
Ravi Salgia, Rebecca Pharaon, Isa Mambetsariev, Arin Nam, Martin Sattler
Summary: KRAS, a common driver in solid tumors such as NSCLC, was initially considered undruggable due to lack of specific small-molecule inhibitors. However, with a better understanding of its transformation mechanisms and the development of immunological approaches targeting KRAS neoantigens, a race for approved therapies has emerged for KRAS mutant NSCLC patients.
CELL REPORTS MEDICINE
(2021)
Article
Oncology
Ella A. Eklund, Clotilde Wiel, Henrik Fagman, Levent M. Akyurek, Sukanya Raghavan, Jan Nyman, Andreas Hallqvist, Volkan Sayin
Summary: This retrospective study investigated the impact of KRAS mutational status on clinical outcome in patients with metastatic non-small cell lung cancer (NSCLC). The results showed that KRAS(MUT) patients had better response to immune checkpoint blockade (ICB) but worse response to platinum doublet chemotherapy (PT). Additionally, KRAS(WT) patients with high PD-L1 expressing tumors responded better to PT than ICB.
Review
Oncology
Mingying Xie, Xiaoling Xu, Yun Fan
Summary: NSCLC, particularly with KRAS mutations, remains difficult to treat due to limited targeted therapies. New small-molecule KRAS G12C inhibitors show promise in treating KRAS-mutant NSCLC. Additionally, immune efficacy has been observed in patients with KRAS mutations undergoing immunotherapy.
FRONTIERS IN ONCOLOGY
(2021)
Article
Multidisciplinary Sciences
Tereza Vaclova, Atanu Chakraborty, James Sherwood, Sarah Ross, Danielle Carroll, J. Carl Barrett, Julian Downward, Elza C. de Bruin
Summary: The study investigates the co-occurrence of additional KRAS mutations with KRAS G12C in non-small cell lung cancer (NSCLC) tumors and its impact on cellular response to G12C-specific inhibitors. The results show that KRAS c.35G>T mutation most frequently co-occurred with KRAS G12C and led to cellular resistance to G12C inhibitors. Therefore, comprehensive genotyping of KRAS tumors is necessary for optimal patient selection for treatment with a KRAS G12C inhibitor.
SCIENTIFIC REPORTS
(2022)
Article
Oncology
Namrata S. Patil, Barzin Y. Nabet, Soeren Mueller, Hartmut Koeppen, Wei Zou, Jennifer Giltnane, Amelia Au-Yeung, Shyam Srivats, Jason H. Cheng, Chikara Takahashi, Patricia E. de Almeida, Avantika S. Chitre, Jane L. Grogan, Linda Rangell, Sangeeta Jayakar, Maureen Peterson, Allison W. Hsia, William E. O'Gorman, Marcus Ballinger, Romain Banchereau, David S. Shames
Summary: The study revealed that inhibitors of the PD-1/PD-L1 signaling axis have a significant overall survival benefit for non-small cell lung cancer (NSCLC) patients. Transcriptomic analysis and single-cell RNA sequencing showed that B and plasma cells play an important role in the efficacy of PD-L1 blockade in NSCLC.
Article
Oncology
Ayako Shiono, Hisao Imai, Satoshi Wasamoto, Takeshi Tsuda, Yoshiaki Nagai, Hiroyuki Minemura, Yutaka Yamada, Takayuki Kishikawa, Yukihiro Umeda, Hiroki Takechi, Ou Yamaguchi, Atsuto Mouri, Kyoichi Kaira, Hirokazu Taniguchi, Koichi Minato, Hiroshi Kagamu
Summary: The purpose of this study was to assess the effectiveness and tolerability of atezolizumab plus carboplatin and etoposide combination chemotherapy in elderly patients with extensive-disease small-cell lung cancer (ED-SCLC). The results showed that despite hematologic toxicities, atezolizumab, carboplatin, and etoposide combination chemotherapy demonstrated favorable effectiveness and acceptable toxicity in elderly patients. Therefore, it could be the preferred standard treatment modality for elderly patients with ED-SCLC.
Article
Oncology
Ken Masubuchi, Hisao Imai, Satoshi Wasamoto, Takeshi Tsuda, Hiroyuki Minemura, Yoshiaki Nagai, Yutaka Yamada, Takayuki Kishikawa, Yukihiro Umeda, Ayako Shiono, Hiroki Takechi, Jun Shiihara, Kyoichi Kaira, Kenya Kanazawa, Hirokazu Taniguchi, Takayuki Kaburagi, Hiroshi Kagamu, Koichi Minato
Summary: This study evaluated the relationship between PFS, PPS, and OS in relapsed ED-SCLC patients treated with atezolizumab plus carboplatin and etoposide as first-line therapy. The results showed a strong correlation between PPS and OS, and a moderate correlation between PFS and OS.
Article
Oncology
Takeshi Tsuda, Hisao Imai, Yoshiaki Nagai, Yukihiro Umeda, Ayako Shiono, Jun Shiihara, Ou Yamaguchi, Atsuto Mouri, Kyoichi Kaira, Tamotsu Ishizuka, Hirokazu Taniguchi, Hiroshi Kagamu
Summary: This study aimed to explore the significance of adding immune checkpoint inhibitors in the treatment of malignancies, including lung cancer. A retrospective analysis was conducted on 16 patients with extensive disease small cell lung cancer who received atezolizumab in combination with carboplatin and etoposide therapy. The results showed that adding atezolizumab to carboplatin and etoposide combination chemotherapy demonstrated favorable efficacy and acceptable toxicity in extensive disease small cell lung cancer.
Article
Oncology
Satoshi Wasamoto, Hisao Imai, Takeshi Tsuda, Yoshiaki Nagai, Hiroyuki Minemura, Yutaka Yamada, Yukihiro Umeda, Takayuki Kishikawa, Ayako Shiono, Yuki Kozu, Jun Shiihara, Ou Yamaguchi, Atsuto Mouri, Kyoichi Kaira, Kenya Kanazawa, Hirokazu Taniguchi, Takayuki Kaburagi, Koichi Minato, Hiroshi Kagamu
Summary: This study aimed to investigate whether the Glasgow prognostic score (GPS), neutrophil-to-lymphocyte ratio (NLR), and body mass index (BMI) can predict the effectiveness of first-line atezolizumab plus carboplatin and etoposide therapy in patients with extensive-disease SCLC. The results showed that GPS was significantly associated with progression-free survival (PFS) and overall survival (OS) rates, suggesting that GPS might be useful for evaluating therapeutic outcomes in these patients.
FRONTIERS IN ONCOLOGY
(2023)
Letter
Oncology
Kyoichi Kaira, Tomohiro Ikezawa, Tsutomu Inoue, Hisao Imai, Hirokazu Okada, Hiroshi Kagamu
JOURNAL OF CHEMOTHERAPY
(2023)
Article
Health Care Sciences & Services
Yukiyoshi Fujita, Hisao Imai, Eriko Hiruta, Takashi Masuno, Shigeki Yamazaki, Hajime Tanaka, Teruhiko Kamiya, Mitsuru Sandoh, Satoshi Takei, Kazuya Arai, Hiromi Nishiba, Junnosuke Mogi, Shiro Koizuka, Taeko Saito, Kyoko Obayashi, Kyoichi Kaira, Koichi Minato
Summary: This multicenter retrospective study aimed to assess the efficacy and safety of naldemedine in cancer patients with ECOG performance status 3 and 4. The results showed that 66.1% of patients responded to naldemedine, and there was a significant increase in defecation frequency for most patients. Diarrhea was the most common adverse event, but most cases were mild or moderate.
JOURNAL OF PALLIATIVE MEDICINE
(2023)
Article
Oncology
Kyoichi Kaira, Ou Yamaguchi, Ichiro Naruse, Yukihiro Umeda, Takeshi Honda, Satoshi Watanabe, Kosuke Ichikawa, Shin Yanagisawa, Norimitsu Kasahara, Tetsuya Higuchi, Kosuke Hashimoto, Yu Miura, Ayako Shiono, Atsuto Mouri, Hisao Imai, Kunihiko Iizuka, Tamotsu Ishizuka, Koichi Minato, Satoshi Suda, Hiroshi Kagamu, Keita Mori, Nobuhiko Seki, Ichiei Kuji
Summary: The study compared different response criteria using CT and PET in patients with advanced NSCLC after PD-1 blockade, and found that the EORTC criteria based on MTV and TLG were effective for response assessment at 4 weeks after treatment.
Article
Oncology
Takashi Kasai, Kiyoshi Mori, Yoichi Nakamura, Nobuhiko Seki, Yasuko Ichikawa, Haruhiro Saito, Tetsuro Kondo, Kazuo Nishikawa, Satoshi Otsu, Akihiro Bessho, Hiroshi Tanaka, Hiroyuki Yamaguchi, Takayuki Kaburagi, Hisao Imai, Keita Mori, Junya Ohtake, Hiroaki Okamoto
Summary: The addition of bevacizumab to cisplatin and pemetrexed combination therapy as maintenance treatment prolongs progression-free survival in patients with untreated, advanced, non-squamous NSCLC. Early response to induction therapy and pretreatment monocytic myeloid-derived suppressor cell counts may be associated with the survival benefit of adding bevacizumab.
Article
Oncology
Hisao Imai, Satoshi Wasamoto, Takeshi Tsuda, Yoshiaki Nagai, Takayuki Kishikawa, Ken Masubuchi, Takashi Osaki, Yosuke Miura, Yukihiro Umeda, Akihiro Ono, Hiroyuki Minemura, Yutaka Yamada, Junichi Nakagawa, Yuki Kozu, Hirokazu Taniguchi, Hiromitsu Ohta, Takashi Kasai, Kyoichi Kaira, Hiroshi Kagamu
Summary: We investigated the predictive factors for the response to Pemb-Plt-PEM combination therapy in non-sq NSCLC. Our results showed that NLR and BMI can serve as prognostic indicators, with NLR predicting PFS and OS, and BMI predicting OS.
Article
Oncology
Kyoichi Kaira, Hisao Imai, Atsuto Mouri, Kosuke Hashimoto, Yu Miura, Ayako Shiono, Ou Yamaguchi, Kunihiko Kobayashi, Tomonori Kawasaki, Masanori Yasuda, Hiroshi Kagamu
Summary: VEGF is identified as a resistant mechanism to EGFR-TKIs in advanced NSCLC with EGFR mutations. High expression of VEGFR2 and VEGF-C is associated with poor performance status and female sex. VEGFR2 is a prognostic factor in EGFR del19 mutation patients treated with osimertinib, while co-high expression of VEGFR2 and VEGF-C predicts survival outcomes in EGFR L858R mutation patients.
Article
Medicine, General & Internal
Teruhiko Kamiya, Hisao Imai, Yukiyoshi Fujita, Eriko Hiruta, Takashi Masuno, Shigeki Yamazaki, Hajime Tanaka, Mitsuru Sandoh, Satoshi Takei, Kazuya Arai, Hiromi Nishiba, Junnosuke Mogi, Shiro Koizuka, Taeko Saito, Kyoko Obayashi, Kyoichi Kaira, Koichi Minato
Summary: This study aimed to evaluate the efficacy and safety of naldemedine in patients with hepatobiliary pancreatic cancer receiving opioid analgesics. The results showed that naldemedine effectively increased the frequency of bowel movements in patients with minimal side effects, making it a viable treatment option for these patients.
MEDICINA-LITHUANIA
(2023)
Article
Oncology
Akitoshi Yanagihara, Satoshi Yamasaki, Kosuke Hashimoto, Ryo Taguchi, Tetsuya Umesaki, Hisao Imai, Kyoichi Kaira, Hiroyuki Nitanda, Hirozo Sakaguchi, Hironori Ishida, Kunihiko Kobayashi, Katsuhisa Horimoto, Hiroshi Kagamu
Summary: Peripheral Th7R cell can predict disease-free survival and guide perioperative drug therapy in patients with early-stage lung cancer.
CANCER RESEARCH COMMUNICATIONS
(2023)
Article
Oncology
Ayako Shiono, Hisao Imai, Tsugumi Satou, Ryo Taguchi, Naoki Takahashi, Ryuichi Azuma, Ou Yamaguchi, Kosuke Hashimoto, Erika Naito, Hidetoshi Iemura, Yu Miura, Atsuto Mouri, Kyoichi Kaira, Kunihiko Kobayashi, Hiroshi Kagamu
Summary: This article reports a case of multi-site recurrence in a patient with MALT lymphoma of the orbit. The thickened lesion in the pleural effusion suggested the possibility of recurrence and further diagnosis was performed.
Article
Oncology
Hisao Imai, Kyoichi Kaira, Ken Masubuchi, Koichi Minato
Summary: The effectiveness and feasibility of intrapericardial administration of carboplatin (CBDCA) after catheter drainage in lung cancer-associated malignant pericardial effusion (MPE) patients were evaluated in this study. The results showed that 66.7% of the cases had controlled MPE 30 days after CBDCA injection. The patients exhibited promising responses to the treatment.