HGF/c-MET pathway in cancer: from molecular characterization to clinical evidence DOI
Jianjiang Fu, Xiaorui Su, Zhihua Li

et al.

Oncogene, Journal Year: 2021, Volume and Issue: 40(28), P. 4625 - 4651

Published: June 18, 2021

Language: Английский

Sotorasib for Lung Cancers with KRAS p.G12C Mutation DOI Open Access
Ferdinandos Skoulidis, Bob T. Li, Grace K. Dy

et al.

New England Journal of Medicine, Journal Year: 2021, Volume and Issue: 384(25), P. 2371 - 2381

Published: June 4, 2021

Sotorasib showed anticancer activity in patients with KRAS p.G12C–mutated advanced solid tumors a phase 1 study, and particularly promising was observed subgroup of non–small-cell lung cancer (NSCLC).

Language: Английский

Citations

1267
The Challenges of Tumor Mutational Burden as an Immunotherapy Biomarker DOI Creative Commons
Denis L. Jardim, Aaron M. Goodman, Débora De Melo Gagliato

et al.

Cancer Cell, Journal Year: 2020, Volume and Issue: 39(2), P. 154 - 173

Published: Oct. 30, 2020

Language: Английский

Citations

828
KRAS mutation: from undruggable to druggable in cancer DOI Creative Commons

Lamei Huang,

Zhixing Guo, Fang Wang

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2021, Volume and Issue: 6(1)

Published: Nov. 15, 2021

Abstract Cancer is the leading cause of death worldwide, and its treatment outcomes have been dramatically revolutionised by targeted therapies. As most frequently mutated oncogene, Kirsten rat sarcoma viral oncogene homologue (KRAS) has attracted substantial attention. The understanding KRAS constantly being updated numerous studies on in initiation progression cancer diseases. However, deemed a challenging therapeutic target, even “undruggable”, after drug-targeting efforts over past four decades. Recently, there surprising advances directly drugs for KRAS, especially (G12C) inhibitors, such as AMG510 (sotorasib) MRTX849 (adagrasib), which obtained encouraging results clinical trials. Excitingly, was first to be approved use this year. This review summarises recent fundamental aspects relationship between mutations tumour immune evasion, new progress targeting particularly (G12C). Moreover, possible mechanisms resistance inhibitors combination therapies are summarised, with view providing best regimen individualised achieving truly precise treatment.

Language: Английский

Citations

626
Oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up DOI Creative Commons
Lizza E.L. Hendriks,

Keith M. Kerr,

Jessica Menis

et al.

Annals of Oncology, Journal Year: 2023, Volume and Issue: 34(4), P. 339 - 357

Published: Jan. 23, 2023

Language: Английский

Citations

436
Clinical implications of intratumor heterogeneity: challenges and opportunities DOI Creative Commons
Santiago Ramón y Cajal, Marta Sesé,

Claudia Capdevila

et al.

Journal of Molecular Medicine, Journal Year: 2020, Volume and Issue: 98(2), P. 161 - 177

Published: Jan. 22, 2020

Abstract In this review, we highlight the role of intratumoral heterogeneity, focusing on clinical and biological ramifications phenomenon poses. Intratumoral heterogeneity arises through complex genetic, epigenetic, protein modifications that drive phenotypic selection in response to environmental pressures. Functionally, provides tumors with significant adaptability. This ranges from mutual beneficial cooperation between cells, which nurture features such as growth metastasis, narrow escape survival clonal cell populations have adapted thrive under specific conditions hypoxia or chemotherapy. These dynamic intercellular interplays are guided by a Darwinian landscape tumor microenvironment. Understanding involved drivers functional consequences is challenging but also promises provide novel insight needed confront problem therapeutic resistance tumors.

Language: Английский

Citations

389
Targeted Therapy and Checkpoint Immunotherapy in Lung Cancer DOI
Roberto Ruiz‐Cordero, W. Patrick Devine

Surgical pathology clinics, Journal Year: 2020, Volume and Issue: 13(1), P. 17 - 33

Published: Jan. 28, 2020

Language: Английский

Citations

373
The MAPK and AMPK signalings: interplay and implication in targeted cancer therapy DOI Creative Commons
Jimin Yuan, Xiaoduo Dong, Jiajun Yap

et al.

Journal of Hematology & Oncology, Journal Year: 2020, Volume and Issue: 13(1)

Published: Aug. 17, 2020

Abstract Cancer is characterized as a complex disease caused by coordinated alterations of multiple signaling pathways. The Ras/RAF/MEK/ERK (MAPK) one the best-defined pathways in cancer biology, and its hyperactivation responsible for over 40% human cases. To drive carcinogenesis, this promotes cellular overgrowth turning on proliferative genes, simultaneously enables cells to overcome metabolic stress inhibiting AMPK signaling, key singular node metabolism. Recent studies have shown that can also reversibly regulate hyperactive MAPK phosphorylating components, RAF/KSR family kinases, which affects not only carcinogenesis but outcomes targeted therapies against signaling. In review, we will summarize current proceedings how MAPK-AMPK signalings interplay with each other well implications clinic treatment inhibition modulators, discuss exploitation combinatory targeting both novel therapeutic intervention.

Language: Английский

Citations

360
The current state of the art and future trends in RAS-targeted cancer therapies DOI Open Access
Salman R. Punekar, Vamsidhar Velcheti, Benjamin G. Neel

et al.

Nature Reviews Clinical Oncology, Journal Year: 2022, Volume and Issue: 19(10), P. 637 - 655

Published: Aug. 26, 2022

Language: Английский

Citations

319
A targetable CoQ-FSP1 axis drives ferroptosis- and radiation-resistance in KEAP1 inactive lung cancers DOI Creative Commons
Pranavi Koppula, Guang Lei, Yilei Zhang

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 22, 2022

Targeting ferroptosis, a unique cell death modality triggered by unrestricted lipid peroxidation, in cancer therapy is hindered our incomplete understanding of ferroptosis mechanisms under specific genetic contexts. KEAP1 (kelch-like ECH associated protein 1) frequently mutated or inactivated lung cancers, and mutant cancers are refractory to most therapies, including radiotherapy. In this study, we identify suppressor 1 (FSP1, also known as AIFM2) transcriptional target nuclear factor erythroid 2-related 2 (NRF2) reveal that the ubiquinone (CoQ)-FSP1 axis mediates ferroptosis- radiation- resistance deficient cells. We further show pharmacological inhibition CoQ-FSP1 sensitizes cells patient-derived xenograft tumors radiation through inducing ferroptosis. Together, study identifies key downstream effector KEAP1-NRF2 pathway potential therapeutic for treating cancers.

Language: Английский

Citations

287
The powerful world of antisense oligonucleotides: From bench to bedside DOI Creative Commons
Anaïs M. Quéméner,

Laura Bachelot,

Anne Forestier

et al.

Wiley Interdisciplinary Reviews - RNA, Journal Year: 2020, Volume and Issue: 11(5)

Published: March 31, 2020

Abstract Antisense oligonucleotides (ASOs) represent a new and highly promising class of drugs for personalized medicine. In the last decade, major chemical developments improvements backbone structure ASOs have transformed them into true approved commercialized drugs. target both DNA RNA, including pre‐mRNA, mRNA, ncRDA, based on sequence complementary. They are designed to be specific each identified molecular genetic alteration restore normal, physiological situation. Thus, characterization underpinning mechanisms alterations that sustain pathology is critical accurate ASO‐design. can used cure rare common diseases, such as orphan cancer. Through pioneering examples, this review shows versatility action provide with potential capacity achieve custom treatment, revolutionizing This article categorized under: RNA in Disease Development > Interactions Proteins Other Molecules Small Molecule–RNA

Language: Английский

Citations

234