ALK Targeted Therapy

ALK Targeted Therapy: Introduction

The anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that is aberrant in a variety of malignancies. For example, activating missense mutations within full length ALK are found in a subset of neuroblastomas. By contrast, ALK fusions are found in anaplastic large cell lymphoma, colorectal cancer, inflammatory myofibroblastic tumor non-small cell lung cancer, and ovarian cancer. All ALK fusions contain the entire ALK tyrosine kinase domain. To date, those tested biologically possess oncogenic activity in vitro and in vivo. ALK fusions and copy number gains have been observed in renal cell carcinoma. Finally, ALK copy number and protein expression aberrations have also been observed in rhabdomyosarcoma.
The various N-terminal fusion partners promote dimerization and therefore constitutive kinase activity. Signaling downstream of ALK fusions results in activation of cellular pathways known to be involved in cell growth and cell proliferation.

ALK Targeted Therapy: Lung Cancer

More recently, in 2007 a translocation in the gene encoding the receptor tyrosine kinase anaplastic lymphoma kinase (ALK),
leading to the expression of ALK fusion proteins, was identified as an oncogenic driver in a subset of patients with non small cell lung cancer. ALK rearrangements are found in approximately 3% of unselected patients with NSCLC. ALK-positive non small cell lung cancer has been associated with a younger patient population than that associated with EGFR mutations and that associated with wild-type ALK and EGFR. ALK positive patients are also generally never-smokers or are light smokers, and predominantly have adenocarcinoma. Data indicating the prognosis of patients with ALK-positive non small cell lung cancer compared to ALK-negative non small cell lung cancer are inconclusive. As ALK tyrosine kinase is required for oncogenesis, inhibition by a tyrosine kinase inhibitor should provide therapeutic efficacy.

ALK Targeted Therapy: Anaplastic Large Cell Lymphoma

Anaplastic large cell lymphoma (ALCL), anaplastic lymphoma kinase (ALK)-positive (ALK+ ALCL) is an aggressive CD30-positive T-cell lymphoma that exhibits a chromosomal translocation involving the ALK gene and the expression of ALK protein. The challenges in studying new drugs in ALK+ anaplastic large cell lymphoma are disease rarity and high cure rate with standard chemotherapy. However, some patients do present with high risk disease and sub-optimal remissions. Nevertheless, the development of novel therapies targeting CD30 and ALK is a major advance in the treatment of anaplastic large cell lymphoma.

Targeted Therapy
What is Targeted Therapy
Targeted Therapy: Targets
Targeted Therapy for Cancer
Targeted Therapy for Kidney Cancer
Targeted Therapy for Liver Cancer
Colorectal Cancer Targeted Therapy
What is Targeted Therapy for Cancer
Targeted Therapy for Leukemia
Targeted Therapy for Pancreatic Cancer
Prostate Cancer Targeted Therapy
Targeted Therapy for Ovarian Cancer
Melanoma Targeted Therapy
Targeted Therapy for Lung Cancer
Targeted Therapy for Breast Cancer
EGFR Targeted Therapy
EGFR Targeted Therapy for Breast Cancer
EGFR Targeted Therapy for Colorectal Cancer
EGFR Targeted Therapy for Head and Neck Cancer
EGFR Targeted Therapy for Non-Small-Cell Lung Cancer
EGFR Targeted Therapy for Ovarian Cancer
EGFR Targeted Therapy for Pancreatic Cancer
HER2 Targeted Therapy
HER2 Targeted Therapy for Breast Cancer
HER2 Targeted Therapy for Colorectal Cancer
Her2 targeted therapy for Ovarian cancer
VEGF Targeted Therapy
VEGF Targeted Therapy for Breast Cancer
VEGF Targeted Therapy for Lung Cancer
VEGF Targeted Therapy for Prostate Cancer
VEGF Targeted Therapy for Colorectal Cancer
BRAF Targeted Therapy
BRAF Targeted Therapy for Melanoma
BRAF Targeted Therapy for Lung Cancer
ALK Targeted Therapy
ALK Targeted Therapy for Lung Cancer
ALK Targeted Therapy for Anaplastic Large Cell Lymphoma
Immune Checkpoint Targeted Therapy
Targeted Therapy Drugs
Targeted Therapy Drugs: Elotuzumab
Targeted Therapy Drugs: Necitumumab
Targeted Therapy Drugs: Daratumumab
Targeted Therapy Drugs: Ramucirumab
Targeted Therapy Drugs: Trastuzumab
Targeted Therapy Drugs: Vemurafenib
Targeted Therapy Drugs: Crizotinib
The Differences between Chemotherapy and Targeted Therapy
Side Effects of Targeted Therapy
Oral Targeted Therapy
Targeted Therapy Resistance
How does Targeted Therapy Work