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 12873

Special Issue Editor


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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 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

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Keywords

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

Published Papers (6 papers)

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Review

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
Viewed by 696
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
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
Viewed by 997
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
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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 5 | Viewed by 1726
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
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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 - 08 Aug 2023
Cited by 1 | Viewed by 2911
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
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 1 | Viewed by 2339
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
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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 7 | Viewed by 3414
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
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