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Targeted therapy in cancer

  • Review Article
  • Published:
Cancer Chemotherapy and Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

To describe the emergence of targeted therapies that have led to significant breakthroughs in cancer therapy and completed or ongoing clinical trials of novel agents for the treatment of patients with advanced cancer.

Methods

The literature was systematically reviewed, based on clinical experience and the use of technologies that improved our understanding of carcinogenesis.

Results

Genomics and model systems have enabled the validation of novel therapeutic strategies. Tumor molecular profiling has enabled the reclassification of cancer and elucidated some mechanisms of disease progression or resistance to treatment, the heterogeneity between primary and metastatic tumors, and the dynamic changes of tumor molecular profiling over time. Despite the notable technologic advances, there is a gap between the plethora of preclinical data and the lack of effective therapies, which is attributed to suboptimal drug development for “driver” alterations of human cancer, the high cost of clinical trials and available drugs, and limited access of patients to clinical trials. Bioinformatic analyses of complex data to characterize tumor biology, function, and the dynamic tumor changes in time and space may improve cancer diagnosis. The application of discoveries in cancer biology in clinic holds the promise to improve the clinical outcomes in a large scale of patients with cancer. Increased harmonization between discoveries, policies, and practices will expedite the development of anticancer drugs and will accelerate the implementation of precision medicine.

Conclusions

Combinations of targeted, immunomodulating, antiangiogenic, or chemotherapeutic agents are in clinical development. Innovative adaptive study design is used to expedite effective drug development.

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Abbreviations

AR:

Androgen receptor

CSCs:

Cancer stem-like cells

CRC:

Colorectal cancer

CR:

Complete response

DFS:

Disease-free survival

DLTs:

Dose-limiting toxicities

EGFR:

Epidermal growth factor receptor

ERK:

Extracellular signal-regulated kinase

FGFR:

Fibroblast growth factor receptor

FDA:

Food and drug administration

GIST:

Gastrointestinal stromal tumors

GSIs:

Non-selective γ-secretase inhibitors

HR:

Hazard ratio

HGF:

Hepatocyte growth factor

HER2:

Human epidermal growth factor receptor 2

IGF:

Insulin-like growth factor

KIT:

Tyrosine-protein kinase

mTOR:

Mammalian target of rapamycin

mTORC1:

mTOR complex 1

mTORC2:

mTOR complex 2

MTD:

Maximum tolerated dose

MAPK:

Mitogen-activated protein kinase

MDM2:

Murine double minute 2

NSCLC:

Non-small cell lung cancer

OS:

Overall survival

PTEN:

Phosphatase and tensin homolog

PtdIns:

Phosphatidylinositols

PI3K:

Phosphatidylinositol 3-kinase

PR:

Partial response

PFS:

Progression-free survival

RAF:

Rapidly accelerated fibrosarcoma

RAPTOR:

Regulatory-associated protein of mTOR

RICTOR:

Rapamycin-insensitive companion of mTOR

SCF:

Stem cell factor

SCC:

Squamous cell carcinoma

T-ALL:

T cell acute lymphoblastic leukemia

TCRβ:

T cell receptor beta

T-DM1:

Trastuzumab emtansine (ado-trastuzumab emtansine)

PIP3 :

Triphosphate

TKIs:

Tyrosine kinase inhibitors

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Acknowledgments

This work was supported by the National Cancer Institute at the National Institutes of Health under Grant P30CA016672.

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  1. Department of Investigational Cancer Therapeutics, Unit 455, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA

    Apostolia-Maria Tsimberidou

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Tsimberidou, AM. Targeted therapy in cancer. Cancer Chemother Pharmacol 76, 1113–1132 (2015). https://doi.org/10.1007/s00280-015-2861-1

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