Targeted Therapy Resistance

Targeted Therapy Resistance: Introduction

Resistance to targeted therapy remains a major challenge in oncology. Resistance comes in two flavors: (1) early intrinsic resistance (also known as innate or de novo resistance) or fast adaptive tumor responses, and (2) late acquired resistance, resulting from clonal evolution of resistant variants.

Targeted Therapy Resistance: Mechanism

It is revealed recurrent somatic alterations in several genes are considered to be drivers of oncogenesis. They activate crucial oncoproteins such as RAS, BRAF, EGFR, PIK3CA, ALK, BCR-ABL and many others. These driver alterations can give rise to a tumor dependency on a particular signaling pathway or module. These dependencies, called ‘oncogene addiction’, can result from activation of genes that stimulate a pathway or inactivation of genes that inhibit a signaling pathway. Tumor dependencies can also be the result of other factors, like hormone dependency or lineage dependency. The addiction of certain cancer types to specific signaling pathways or modules in those pathways creates an Achilles heel for tumor maintenance that can be exploited therapeutically. However, examples of pure ‘oncogene addiction’ from a single oncogenic event are rare. Most cancers contain many mutations, making such tumors potentially less dependent on a single oncogenic event. Another complication is that signaling pathways are interconnected and these interactions are often dynamic. A third factor limiting the success of targeted single-agent therapy is the heterogeneity of tumors, especially in the advanced or metastatic setting.

Targeted Therapy Resistance: Dealing with it

An understanding of the recurrent patterns of resistance is necessary to design strategies to overcome intrinsic resistance and delay acquired resistance to targeted cancer drugs. To address this, significant efforts are now underway to (1) develop better drugs or more effective drug combinations to fully suppress the oncogenic signaling pathways and (2) development of non-invasive assays to monitor drug response and the emergence of drug resistance

Targeted Therapy Resistance: Reference

Groenendijk F H et al. Drug resistance to targeted therapies: Deja vu all over again[J]. Molecular oncology, 2014, 8(6): 1067-1083.

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