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Predictive biomarkers in precision medicine and drug development against lung cancer.

Fang B, Mehran RJ, Heymach JV, Swisher SG - Chin J Cancer (2015)

Bottom Line: However, because such therapeutic drugs often benefit only a limited number of patients, the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.This review discusses the molecular heterogeneity of lung cancer pathogenesis; predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), and immune checkpoints; biomarkers associated with resistance to these therapeutics; and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. bfang@mdanderson.org.

ABSTRACT
The molecular characterization of various cancers has shown that cancers with the same origins, histopathologic diagnoses, and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis. A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified. Therapeutic agents targeting some of these cancer drivers have been successfully developed, resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients. However, because such therapeutic drugs often benefit only a limited number of patients, the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies. Thus, biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development. This review discusses the molecular heterogeneity of lung cancer pathogenesis; predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), and immune checkpoints; biomarkers associated with resistance to these therapeutics; and approaches to identify predictive biomarkers in anticancer drug development. The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate. Additionally, such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.

No MeSH data available.


Related in: MedlinePlus

Chemical structures of anti-EGFR therapeutic agents.
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Fig3: Chemical structures of anti-EGFR therapeutic agents.

Mentions: Epidermal growth factor receptor, a major driver in lung tumorigenesis, has been extensively investigated as a target for anticancer therapy. As noted above, activating EGFR mutations are detected in substantial numbers of lung cancer patients and are more commonly observed in women and non-smokers [27, 43–46]. The finding that EGFR mutations in primary lung cancer are associated with sensitivity to EGFR inhibitors gefitinib and erlotinib [44, 60, 61] contributed greatly to the final approval of these therapeutics for the treatment of lung cancer. Subsequently, EGFR gene mutations have served as biomarkers in the clinic for the identification of responders to EGFR inhibitors. Both gefitinib and erlotinib (Figure 3) are the first choice for therapy in lung cancer patients whose tumors harbor EGFR mutations and are reported to significantly prolong progression-free survival (PFS) in patients with EGFR-mutant lung cancer [62–64]. Icotinib, which has a clinical efficacy similar to that of gefitinib but less adverse effects [65], is approved for the treatment of EGFR-mutant lung cancer in China.Figure 3


Predictive biomarkers in precision medicine and drug development against lung cancer.

Fang B, Mehran RJ, Heymach JV, Swisher SG - Chin J Cancer (2015)

Chemical structures of anti-EGFR therapeutic agents.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4593363&req=5

Fig3: Chemical structures of anti-EGFR therapeutic agents.
Mentions: Epidermal growth factor receptor, a major driver in lung tumorigenesis, has been extensively investigated as a target for anticancer therapy. As noted above, activating EGFR mutations are detected in substantial numbers of lung cancer patients and are more commonly observed in women and non-smokers [27, 43–46]. The finding that EGFR mutations in primary lung cancer are associated with sensitivity to EGFR inhibitors gefitinib and erlotinib [44, 60, 61] contributed greatly to the final approval of these therapeutics for the treatment of lung cancer. Subsequently, EGFR gene mutations have served as biomarkers in the clinic for the identification of responders to EGFR inhibitors. Both gefitinib and erlotinib (Figure 3) are the first choice for therapy in lung cancer patients whose tumors harbor EGFR mutations and are reported to significantly prolong progression-free survival (PFS) in patients with EGFR-mutant lung cancer [62–64]. Icotinib, which has a clinical efficacy similar to that of gefitinib but less adverse effects [65], is approved for the treatment of EGFR-mutant lung cancer in China.Figure 3

Bottom Line: However, because such therapeutic drugs often benefit only a limited number of patients, the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies.This review discusses the molecular heterogeneity of lung cancer pathogenesis; predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), and immune checkpoints; biomarkers associated with resistance to these therapeutics; and approaches to identify predictive biomarkers in anticancer drug development.The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA. bfang@mdanderson.org.

ABSTRACT
The molecular characterization of various cancers has shown that cancers with the same origins, histopathologic diagnoses, and clinical stages can be highly heterogeneous in their genetic and epigenetic alterations that cause tumorigenesis. A number of cancer driver genes with functional abnormalities that trigger malignant transformation and that are required for the survival of cancer cells have been identified. Therapeutic agents targeting some of these cancer drivers have been successfully developed, resulting in substantial improvements in clinical symptom amelioration and outcomes in a subset of cancer patients. However, because such therapeutic drugs often benefit only a limited number of patients, the successes of clinical development and applications rely on the ability to identify those patients who are sensitive to the targeted therapies. Thus, biomarkers that can predict treatment responses are critical for the success of precision therapy for cancer patients and of anticancer drug development. This review discusses the molecular heterogeneity of lung cancer pathogenesis; predictive biomarkers for precision medicine in lung cancer therapy with drugs targeting epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 receptor tyrosine kinase (ROS1), and immune checkpoints; biomarkers associated with resistance to these therapeutics; and approaches to identify predictive biomarkers in anticancer drug development. The identification of predictive biomarkers during anticancer drug development is expected to greatly facilitate such development because it will increase the chance of success or reduce the attrition rate. Additionally, such identification will accelerate the drug approval process by providing effective patient stratification strategies in clinical trials to reduce the sample size required to demonstrate clinical benefits.

No MeSH data available.


Related in: MedlinePlus