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Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets...
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Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Molecular Cancer Biology".

Deadline for manuscript submissions: closed (20 March 2024) | Viewed by 35962

Special Issue Editor

Prof. Dr. Tianhong Li

E-Mail Website
Guest Editor
Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Comprehensive Cancer Center, Sacramento, CA, USA
Interests: precision oncology; lung cancer; targeted therapy; biomarkers
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The landscape for the diagnosis and treatment of lung cancer has significantly evolved over the past two decades. The current era of precision medicine in resectable early-stage and non-operable advanced-stage NSCLC mandates the pathohistological evaluation and molecular biomarker testing of tumor specimens at diagnosis. Increasingly, subsequent biomarker testing is essential for selecting appropriate treatment at timepoints of tumor progression throughout the disease course. Significant progress has also been made in expanding the armamentarium of targeted therapies from small molecule tyrosine kinase inhibitors and monoclonal antibodies to covalent bound inhibitors, bispecific antibodies, and antibody–drug conjugants for both known and emerging oncogenic targets. The clinical implementation of precision medicine in lung cancer requires the close collaboration of a multidisciplinary team, along with further technology and knowledge advances in understanding tumor biology and biomarker-guided treatment selection at the patient level. This Special Issue will focus on a series of reviews on recent advances in targeting known and emerging oncogenic targets (such as MET, HER2, and KRAS genomic alterations) in lung adenocarcinomas, lung squamous cell carcinoma, neuroendocrine, small cell lung cancer, and malignant pleural mesothelioma.

Prof. Dr. Tianhong Li
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • precision oncology
  • lung cancer
  • oncogenic target
  • targeted therapy
  • biomarker
  • diagnosis

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Related Special Issue

Published Papers (10 papers)

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30 pages, 1346 KiB  
Review
Preclinical Models for Functional Precision Lung Cancer Research
by Jie-Zeng Yu, Zsofia Kiss, Weijie Ma, Ruqiang Liang and Tianhong Li
Cancers 2025, 17(1), 22; https://doi.org/10.3390/cancers17010022 - 25 Dec 2024
Viewed by 1926
Abstract
Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted [...] Read more.
Patient-centered precision oncology strives to deliver individualized cancer care. In lung cancer, preclinical models and technological innovations have become critical in advancing this approach. Preclinical models enable deeper insights into tumor biology and enhance the selection of appropriate systemic therapies across chemotherapy, targeted therapies, immunotherapies, antibody–drug conjugates, and emerging investigational treatments. While traditional human lung cancer cell lines offer a basic framework for cancer research, they often lack the tumor heterogeneity and intricate tumor–stromal interactions necessary to accurately predict patient-specific clinical outcomes. Patient-derived xenografts (PDXs), however, retain the original tumor’s histopathology and genetic features, providing a more reliable model for predicting responses to systemic therapeutics, especially molecularly targeted therapies. For studying immunotherapies and antibody–drug conjugates, humanized PDX mouse models, syngeneic mouse models, and genetically engineered mouse models (GEMMs) are increasingly utilized. Despite their value, these in vivo models are costly, labor-intensive, and time-consuming. Recently, patient-derived lung cancer organoids (LCOs) have emerged as a promising in vitro tool for functional precision oncology studies. These LCOs demonstrate high success rates in growth and maintenance, accurately represent the histology and genomics of the original tumors and exhibit strong correlations with clinical treatment responses. Further supported by advancements in imaging, spatial and single-cell transcriptomics, proteomics, and artificial intelligence, these preclinical models are reshaping the landscape of drug development and functional precision lung cancer research. This integrated approach holds the potential to deliver increasingly accurate, personalized treatment strategies, ultimately enhancing patient outcomes in lung cancer. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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12 pages, 663 KiB  
Review
Clinical Advances and Challenges in Targeting KRAS Mutations in Non-Small Cell Lung Cancer
by Simone E. Dekker and Lei Deng
Cancers 2024, 16(22), 3885; https://doi.org/10.3390/cancers16223885 - 20 Nov 2024
Cited by 1 | Viewed by 1700 | Correction
Abstract
KRAS mutation is one of the most common oncogenic drivers in non-small cell lung cancer. Since its discovery about four decades ago, drug development targeting KRAS has been met with countless failures. Recently, KRAS G12C, a subvariant of KRAS, became the first druggable [...] Read more.
KRAS mutation is one of the most common oncogenic drivers in non-small cell lung cancer. Since its discovery about four decades ago, drug development targeting KRAS has been met with countless failures. Recently, KRAS G12C, a subvariant of KRAS, became the first druggable KRAS mutation. The efficacy of the first-generation KRAS inhibitor is modest, but with scientific advancement, KRAS G12C inhibitors with higher potency are on the horizon. Additionally, novel therapeutic approaches targeting other KRAS subvariants are also being explored in clinical trials with encouraging early data. We will review the clinical advances and challenges for patients with KRAS-mutated non-small cell lung cancer, with a focus on small molecule inhibitors. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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21 pages, 1809 KiB  
Review
Evolving Precision First-Line Systemic Treatment for Patients with Unresectable Non-Small Cell Lung Cancer
by Tianhong Li, Weijie Ma and Ebaa Al-Obeidi
Cancers 2024, 16(13), 2350; https://doi.org/10.3390/cancers16132350 - 26 Jun 2024
Cited by 5 | Viewed by 5579
Abstract
First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted therapy for a growing number of gain-of-function molecular targets has been shown to improve progression-free survival (PFS) and [...] Read more.
First-line systemic therapy for patients with advanced or metastatic non-small cell lung cancer (NSCLC) has rapidly evolved over the past two decades. First, molecularly targeted therapy for a growing number of gain-of-function molecular targets has been shown to improve progression-free survival (PFS) and overall survival (OS) with favorable toxicity profiles compared to platinum-containing chemotherapy and can be given as first-line systemic therapy in ~25% of patients with NSCLC. Actionable genetic alterations include EGFR, BRAF V600E, and MET exon 14 splicing site-sensitizing mutations, as well as ALK-, ROS1-, RET-, and NTRK-gene fusions. Secondly, inhibitors of programmed cell death protein 1 or its ligand 1 (PD-1/L1) such as pembrolizumab, atezolizumab, or cemiplimab monotherapy have become a standard of care for ~25% of patients with NSCLC whose tumors have high PD-L1 expression (total proportion score (TPS) ≥50%) and no sensitizing EGFR/ALK alterations. Lastly, for the remaining ~50% of patients who are fit and whose tumors have no or low PD-L1 expression (TPS of 0–49%) and no sensitizing EGFR/ALK aberrations, platinum-containing chemotherapy with the addition of a PD-1/L1 inhibitor alone or in combination of a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor improves PFS and OS compared to chemotherapy alone. The objectives of this review are to summarize the current data and perspectives on first-line systemic treatment in patients with unresectable NSCLC and propose a practical algorithm for implementing precision biomarker testing at diagnosis. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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13 pages, 263 KiB  
Review
Emerging New Targets in Systemic Therapy for Malignant Pleural Mesothelioma
by Karen M. Yun and Lyudmila Bazhenova
Cancers 2024, 16(7), 1252; https://doi.org/10.3390/cancers16071252 - 22 Mar 2024
Cited by 3 | Viewed by 3639
Abstract
Malignant pleural mesothelioma (MPM) is a heterogeneous cancer composed of distinct molecular and pathologic subtypes. Unfortunately, MPM is aggressive, and current therapies for advanced, unresectable disease remain limited to cytotoxic chemotherapy and immunotherapy. Our understanding of the genomic landscape of MPM is steadily [...] Read more.
Malignant pleural mesothelioma (MPM) is a heterogeneous cancer composed of distinct molecular and pathologic subtypes. Unfortunately, MPM is aggressive, and current therapies for advanced, unresectable disease remain limited to cytotoxic chemotherapy and immunotherapy. Our understanding of the genomic landscape of MPM is steadily growing, while the discovery of effective targeted therapies in MPM has advanced more slowly than in other solid tumors. Given the prevalence of alterations in tumor suppressor genes in MPM, it has been challenging to identify actionable targets. However, efforts to characterize the genetic signatures in MPM over the last decade have led to a range of novel targeted therapeutics entering early-phase clinical trials. In this review, we discuss the advancements made thus far in targeted systemic therapies in MPM and the future direction of targeted strategies in patients with advanced MPM. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
12 pages, 603 KiB  
Review
Emerging Precision Medicine Approaches for Lung Neuroendocrine Tumors
by Claire K. Mulvey
Cancers 2023, 15(23), 5575; https://doi.org/10.3390/cancers15235575 - 25 Nov 2023
Cited by 3 | Viewed by 2145
Abstract
Well-differentiated lung neuroendocrine tumors (LNETs) are heterogeneous cancers that are increasing in incidence. Treatment options for LNETs have expanded in recent years, and our knowledge of the molecular subtypes has also advanced. Multidisciplinary teams have an established role in personalizing the best treatment [...] Read more.
Well-differentiated lung neuroendocrine tumors (LNETs) are heterogeneous cancers that are increasing in incidence. Treatment options for LNETs have expanded in recent years, and our knowledge of the molecular subtypes has also advanced. Multidisciplinary teams have an established role in personalizing the best treatment for individual patients. Other precision medicine approaches for the treatment of LNETs have lagged behind those for non-small-cell lung cancer, with only rare actionable molecular alterations identified and few established predictive factors to guide therapy selection. However, as summarized in this review, there is increasing potential for personalized treatment of patients with LNETs. In particular, advances in radiotheragnostics may allow us to tailor the treatment of individual patients with NETs in the coming years. These advances may soon deliver the promise of more effective, less toxic treatments and better outcomes for patients with these increasingly common cancers. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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27 pages, 705 KiB  
Review
A Review of Biomarkers and Their Clinical Impact in Resected Early-Stage Non-Small-Cell Lung Cancer
by Weibo Cao, Quanying Tang, Jingtong Zeng, Xin Jin, Lingling Zu and Song Xu
Cancers 2023, 15(18), 4561; https://doi.org/10.3390/cancers15184561 - 14 Sep 2023
Cited by 15 | Viewed by 3311
Abstract
The postoperative survival of early-stage non-small-cell lung cancer (NSCLC) patients remains unsatisfactory. In this review, we examined the relevant literature to ascertain the prognostic effect of related indicators on early-stage NSCLC. The prognostic effects of the epidermal growth factor receptor (EGFR), anaplastic lymphoma [...] Read more.
The postoperative survival of early-stage non-small-cell lung cancer (NSCLC) patients remains unsatisfactory. In this review, we examined the relevant literature to ascertain the prognostic effect of related indicators on early-stage NSCLC. The prognostic effects of the epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), mesenchymal–epithelial transition (MET), C-ros oncogene 1 (ROS1), or tumour protein p53 (TP53) alterations in resected NSCLC remains debatable. Kirsten rat sarcoma viral oncogene homologue (KRAS) alterations indicate unfavourable outcomes in early-stage NSCLC. Meanwhile, adjuvant or neoadjuvant EGFR-targeted agents can substantially improve prognosis in early-stage NSCLC with EGFR alterations. Based on the summary of current studies, resected NSCLC patients with overexpression of programmed death-ligand 1 (PD-L1) had worsening survival. Conversely, PD-L1 or PD-1 inhibitors can substantially improve patient survival. Considering blood biomarkers, perioperative peripheral venous circulating tumour cells (CTCs) and pulmonary venous CTCs predicted unfavourable prognoses and led to distant metastases. Similarly, patients with detectable perioperative circulating tumour DNA (ctDNA) also had reduced survival. Moreover, patients with perioperatively elevated carcinoembryonic antigen (CEA) in the circulation predicted significantly worse survival outcomes. In the future, we will incorporate mutated genes, immune checkpoints, and blood-based biomarkers by applying artificial intelligence (AI) to construct prognostic models that predict patient survival accurately and guide individualised treatment. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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12 pages, 286 KiB  
Review
Small Cell Lung Cancer: Emerging Targets and Strategies for Precision Therapy
by Shruti R. Patel and Millie Das
Cancers 2023, 15(16), 4016; https://doi.org/10.3390/cancers15164016 - 8 Aug 2023
Cited by 14 | Viewed by 6654
Abstract
Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides [...] Read more.
Small cell lung cancer is an aggressive subtype of lung cancer with limited treatment options. Precision medicine has revolutionized cancer treatment for many tumor types but progress in SCLC has been slower due to the lack of targetable biomarkers. This review article provides an overview of emerging strategies for precision therapy in SCLC. Targeted therapies include targeted kinase inhibitors, monoclonal antibodies, angiogenesis inhibitors, antibody–drug conjugates, PARP inhibitors, and epigenetic modulators. Angiogenesis inhibitors and DNA-damaging agents, such as PARP and ATR inhibitors, have been explored in SCLC with limited success to date although trials are ongoing. The potential of targeting DLL3, a NOTCH ligand, through antibody–drug conjugates, bispecific T-cell engagers, and CAR T-cell therapy, has opened up new therapeutic options moving forward. Additionally, new research in epigenetic therapeutics in reversing transcriptional repression, modulating anti-tumor immunity, and utilizing antibody–drug conjugates to target cell surface-specific targets in SCLC are also being investigated. While progress in precision therapy for SCLC has been challenging, recent advancements provide optimism for improved treatment outcomes. However, several challenges remain and will need to be addressed, including drug resistance and tumor heterogeneity. Further research and biomarker-selected clinical trials are necessary to develop effective precision therapies for SCLC patients. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
13 pages, 816 KiB  
Review
Arising Novel Agents in Lung Cancer: Are Bispecifics and ADCs the New Paradigm?
by Amanda Reyes, Rebecca Pharaon, Atish Mohanty and Erminia Massarelli
Cancers 2023, 15(12), 3162; https://doi.org/10.3390/cancers15123162 - 13 Jun 2023
Cited by 3 | Viewed by 3557
Abstract
Lung cancer is one of the most common cancers with the highest mortality. Non-small cell lung cancer (NSCLC) contributes to around 85% of lung cancer diagnoses (vs. 15% for small cell lung cancer). The treatment of NSCLC has vastly changed in the last [...] Read more.
Lung cancer is one of the most common cancers with the highest mortality. Non-small cell lung cancer (NSCLC) contributes to around 85% of lung cancer diagnoses (vs. 15% for small cell lung cancer). The treatment of NSCLC has vastly changed in the last two decades since the development of immunotherapy and targeted therapy against driver mutations. As is the nature of malignancy, cancer cells have acquired resistance to these treatments prompting an investigation into novel treatments and new targets. Bispecific antibodies, capable of targeting multiple substrates at once, and antibody–drug conjugates that can preferentially deliver chemotherapy to tumor cells are examples of this innovation. From our initial evaluation, both treatment modalities appear promising. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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25 pages, 2621 KiB  
Review
Emerging Targeted Therapies in Advanced Non-Small-Cell Lung Cancer
by Shenduo Li, Guilherme Sacchi de Camargo Correia, Jing Wang, Rami Manochakian, Yujie Zhao and Yanyan Lou
Cancers 2023, 15(11), 2899; https://doi.org/10.3390/cancers15112899 - 24 May 2023
Cited by 34 | Viewed by 5505
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC [...] Read more.
Lung cancer remains the leading cause of cancer-related mortality worldwide. Non-small-cell lung cancer (NSCLC) is the most common type and is still incurable for most patients at the advanced stage. Targeted therapy is an effective treatment that has significantly improved survival in NSCLC patients with actionable mutations. However, therapy resistance occurs widely among patients leading to disease progression. In addition, many oncogenic driver mutations in NSCLC still lack targeted agents. New drugs are being developed and tested in clinical trials to overcome these challenges. This review aims to summarize emerging targeted therapy that have been conducted or initiated through first-in-human clinical trials in the past year. Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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1 pages, 133 KiB  
Correction
Correction: Dekker, S.E.; Deng, L. Clinical Advances and Challenges in Targeting KRAS Mutations in Non-Small Cell Lung Cancer. Cancers 2024, 16, 3885
by Simone E. Dekker and Lei Deng
Cancers 2025, 17(1), 98; https://doi.org/10.3390/cancers17010098 - 31 Dec 2024
Viewed by 497
Abstract
In the original publication [...] Full article
(This article belongs to the Special Issue Advances in Precision Medicine: Targeting Known and Emerging Oncogenic Targets in Lung Cancer)
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