Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers

Alshareef, Abdulraheem

doi:10.3390/cancers9110148

Cited by 5 publications

(4 citation statements)

References 99 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ALK has proved an attractive and clinically successful drug target. Of the 10 small-molecule ALK inhibitors undergoing clinical trials, 4 have gained FDA approval, to date [210].…”

Section: Resultsmentioning

confidence: 99%

Clinical development of targeted and immune based anti-cancer therapies

Seebacher

Stacy

Porter

et al. 2019

J Exp Clin Cancer Res

197

131

View full text Add to dashboard Cite

Cancer is currently the second leading cause of death globally and is expected to be responsible for approximately 9.6 million deaths in 2018. With an unprecedented understanding of the molecular pathways that drive the development and progression of human cancers, novel targeted therapies have become an exciting new development for anti-cancer medicine. These targeted therapies, also known as biologic therapies, have become a major modality of medical treatment, by acting to block the growth of cancer cells by specifically targeting molecules required for cell growth and tumorigenesis. Due to their specificity, these new therapies are expected to have better efficacy and limited adverse side effects when compared with other treatment options, including hormonal and cytotoxic therapies. In this review, we explore the clinical development, successes and challenges facing targeted anti-cancer therapies, including both small molecule inhibitors and antibody targeted therapies. Herein, we introduce targeted therapies to epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), human epidermal growth factor receptor 2 (HER2), anaplastic lymphoma kinase (ALK), BRAF, and the inhibitors of the T-cell mediated immune response, cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein-1 (PD-1)/ PD-1 ligand (PD-1 L).

show abstract

“…ALK has proved an attractive and clinically successful drug target. Of the 10 small-molecule ALK inhibitors undergoing clinical trials, 4 have gained FDA approval, to date [210].…”

Section: Resultsmentioning

confidence: 99%

Clinical development of targeted and immune based anti-cancer therapies

Seebacher

Stacy

Porter

et al. 2019

J Exp Clin Cancer Res

197

131

View full text Add to dashboard Cite

show abstract

“…In another example, ALK-TKI resistance in ALK-positive NSCLC has been attributed to mutations in the ALK gene itself or activation of compensatory alternative oncogenic drivers (e.g., MET, EGFR, KRAS, KIT), giving rise to new strategies to overcome resistance mechanisms [12,40]. These have been identified through repeat biopsies of patients who developed resistance, underscoring the importance of longitudinal tracking of tumors -for both identifying targetable resistance mechanisms and monitoring for relapse [41,42].…”

Section: Using Precision Oncology To Match Therapiesmentioning

confidence: 99%

Precision Oncology: a Clinical and Patient Perspective

Lassen

Makaroff²,

Italiano

et al. 2021

Future Oncol.

View full text Add to dashboard Cite

Molecular characterization of tumors has shifted cancer treatment strategies away from nonspecific cytotoxic treatment of histology-specific tumors toward targeting of actionable mutations that can be found across multiple cancer types. The development of high-throughput technologies such as next-generation sequencing, combined with decision support applications and availability of patient databases, has provided tools that optimize disease management. Precision oncology has proven success in improving outcomes and quality of life, as well as identifying and overcoming mechanisms of drug resistance and relapse. Addressing challenges that impede its use will improve matching of therapies to patients. Here we review the current status of precision oncology medicine, emphasizing its impact on patients – what they understand about precision oncology medicine and their hopes for the future.

show abstract

“…ALK recognizes some different ligands, including pleiotrophin and neurite growth-promoting factor 2 (NEGF2). 43 Alterations including ALK fusion, ALK copy-number gain, and activating ALK mutations are found in multiple cancers. 44 ROS1 gene encodes a receptor that belongs to the ALK/leukocyte TK (LTK) and insulin RTK families and, once activated, induces cell proliferation by stimulating MAPK (mitogen-activated protein kinase)/ERK, PI3K/AKT, and JAK/STAT3 (Janus kinase/signal transducers and activators of transcription 3) signaling pathways.…”

Section: Alk/ros1mentioning

confidence: 99%

Druggable targets meet oncogenic drivers: opportunities and limitations of target-based classification of tumors and the role of Molecular Tumor Boards

et al. 2021

View full text Add to dashboard Cite

The therapeutic landscape of cancer is changing rapidly due to the growing number of approved drugs capable of targeting specific genetic alterations. This aspect, together with the development of noninvasive methods for the assessment of somatic mutations in the peripheral blood of patients, generated a growing interest toward a new tumor-agnostic classification system based on 'predictive' biomarkers. The current review article discusses this emerging alternative approach to the classification of cancer and its implications for the selection of treatments. It is suggested that different types of cancers sharing the same molecular profiles could benefit from the same targeted drugs. Although recent clinical trials have demonstrated that this approach cannot be generalized, there are also specific examples that demonstrate the clinical utility of this alternative vision. In this rapidly evolving scenario, a multidisciplinary approach managed by institutional Molecular Tumor Boards is fundamental to interpret the biological and clinical relevance of genetic alterations and the complexity of their relationship with treatment response.

show abstract

Novel Molecular Challenges in Targeting Anaplastic Lymphoma Kinase in ALK-Expressing Human Cancers

Cited by 5 publications

References 99 publications

Clinical development of targeted and immune based anti-cancer therapies

Clinical development of targeted and immune based anti-cancer therapies

Precision Oncology: a Clinical and Patient Perspective

Druggable targets meet oncogenic drivers: opportunities and limitations of target-based classification of tumors and the role of Molecular Tumor Boards

Contact Info

Product

Resources

About