Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2014 Mar 12;106(5):dju044.
doi: 10.1093/jnci/dju044.

Chemotherapy-induced peripheral neurotoxicity and ototoxicity: new paradigms for translational genomics

Lois B Travis  1 , Sophie D Fossa  2 , Howard D Sesso  2 , Robert D Frisina  2 , David N Herrmann  2 , Clair J Beard  2 , Darren R Feldman  2 , Lance C Pagliaro  2 , Robert C Miller  2 , David J Vaughn  2 , Lawrence H Einhorn  2 , Nancy J Cox  2 , M Eileen Dolan  2 ; Platinum Study Group
Affiliations
Review

Chemotherapy-induced peripheral neurotoxicity and ototoxicity: new paradigms for translational genomics

Lois B Travis et al. J Natl Cancer Inst. .

Abstract

In view of advances in early detection and treatment, the 5-year relative survival rate for all cancer patients combined is now approximately 66%. As a result, there are more than 13.7 million cancer survivors in the United States, with this number increasing by 2% annually. For many patients, improvements in survival have been countered by therapy-associated adverse effects that may seriously impair long-term functional status, workplace productivity, and quality of life. Approximately 20% to 40% of cancer patients given neurotoxic chemotherapy develop chemotherapy-induced peripheral neurotoxicity (CIPN), which represents one of the most common and potentially permanent nonhematologic side effects of chemotherapy. Permanent bilateral hearing loss and/or tinnitus can result from several ototoxic therapies, including cisplatin- or carboplatin-based chemotherapy. CIPN and ototoxicity represent important challenges because of the lack of means for effective prevention, mitigation, or a priori identification of high-risk patients, and few studies have applied modern genomic approaches to understand underlying mechanisms/pathways. Translational genomics, including cell-based models, now offer opportunities to make inroads for the first time to develop preventive and interventional strategies for CIPN, ototoxicity, and other treatment-related complications. This commentary provides current perspective on a successful research strategy, with a focus on cisplatin, developed by an experienced, transdisciplinary group of researchers and clinicians, representing pharmacogenomics, statistical genetics, neurology, hearing science, medical oncology, epidemiology, and cancer survivorship. Principles outlined herein are applicable to the construction of research programs in translational genomics with strong clinical relevance and highlight unprecedented opportunities to understand, prevent, and treat long-term treatment-related morbidities.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Example of translational genomic approach. After a genome-wide association study of drug-induced neurotoxicity in patients to identify associated single nucleotide polymorphisms (SNPs; left panel, upper portion), an enrichment analysis for drug-induced cytotoxicity in lymphoblastoid cell line (LCL) models can be performed (117). This analysis identifies single overlapping SNPs correlated with neurotoxicity in patients and drug sensitivity in vitro (left panel, lower portion). Additional analyses determine the degree of heritability explained by the clinical phenotype (ie, drug-induced neurotoxicity) (right panel, top portion). Of SNPs associated with the clinical phenotype, the fraction that overlap with the LCL-based model and the fraction that are cross-tissue expression quantitative trait loci (eQTL) using genome-tissue expression datasets can be estimated (right panel, bottom portion) (137).
Figure 2.
Figure 2.
Pleiotropy among different cancers detected by the Collaborative Oncological Gene–Environment Study (COGS) and previous association studies. Risk-associated loci for each cancer are indicated by chromosomal location, and sharing is indicated by colored lines connecting different cancers. For example, loci at 8q24 are associated with breast, ovarian, prostate, colon, and bladder cancers and with chronic lymphocytic leukemia (CLL) (light-blue lines). Reprinted with permission from Sakoda et al. (128).
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Altekruse S, Kosary C, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2007. National Cancer Institute, Bethesda, MD: National Cancer Institute; 2010. http://seer.cancer.gov/csr/1975_2007/ Accessed February 18, 2014.
    1. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62(4):220–241. - PubMed
    1. Anonymous. Cancer survivors: living longer, and now, better. Lancet. 2004;364(9452):2153–2154. - PubMed
    1. Travis LB, Demark Wahnefried W, Allan JM, et al. Aetiology, genetics and prevention of secondary neoplasms in adult cancer survivors. Nat Rev Clin Oncol. 2013;10(5):289–301. - PubMed
    1. Elena JW, Travis LB, Simonds NI, et al. Leveraging epidemiology and clinical studies of cancer outcomes: recommendations and opportunities for translational research. J Natl Cancer Inst. 2013;105(2):85–94. - PMC - PubMed

Publication types

MeSH terms

Substances