Abstract
Cancer biomarkers have provided great opportunities for improving the management of cancer patients by enhancing the efficiency of early detection, diagnosis, and efficacy of treatment. Every cell type has a unique molecular signature, referred to as biomarkers, which are identifiable characteristics such as levels or activities of a myriad of genes, proteins, or other molecular features.
Biomarkers can facilitate the molecular definition of cancer, provide information about the course of cancer, and predict response to chemotherapy. They offer the hope of early detection as well as tracking disease progression and recurrence. Current progress in the characterization of molecular genetics of HIV-associated cancers may form the basis for improved patient stratification and future targeted or individualized therapies.
Biomarker use for cancer staging and personalization of therapy at the time of diagnosis could improve patient care. This review focuses on the relevance of biomarkers in the most common HIV-associated malignancies, namely, Kaposi sarcoma, non-Hodgkin’s lymphoma, and invasive cervical cancer.
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CITATION: Flepisi et al. Biomarkers of HIV-associated Cancer. Biomarkers in Cancer 2014:6 11–20 doi:10.4137/BIC.S15056.
RECEIVED: March 2, 2014. RESUBMITTED: April 21, 2014. ACCEPTED FOR PUBLICATION: April 23, 2014.
ACADEMIC EDITOR: Barbara Guinn, Editor in Chief
TYPE: Review
FUNDING: This study was supported by, National Research Foundation-German DFG-IRTG project 1522 “HIV/AIDSand associated infectious diseases in Southern Africa” (NRF-IRTG); Columbia University-South Africa (D43) training program for research on HIV associated malignancies; and Harry Crossley foundation research grant. Funding sources have not influenced the content of the paper.
COMPETING INTERESTS: Authors disclose no potential conflicts of interest.
COPYRIGHT: © the authors, publisher and licensee Libertas Academica Limited. This is an open-access article distributed under the terms of the Creative Commons CC-BY-NC 3.0 License.
CORRESPONDENCE: [email protected]
This paper was subject to independent, expert peer review by a minimum of two blind peer reviewers. ll editorial decisions were made by the independent academic editor. ll authors have provided signed confirmation of their compliance with ethical and legal obligations including (but not limited to) use of any copyrighted material, compliance with ICMJE authorship and competing interests disclosure guidelines and, where applicable, compliance with legal and ethical guidelines on human and animal research participants.
Introduction
Cancer is a genetically and clinically diverse disease, whose pathogenesis, aggressiveness, metastatic potential, and response to treatment can be different among individual patients.1
Great variations exist, even between individuals with the same type of cancer, suggesting the role of genetic factors in cancer pathogenesis. The risk of developing cancer is greatly increased in human immunodeficiency virus (HIV) setting, and it is increasingly recognized as a complication of HIV infection.2,3
Cancers with an increased incidence in HIV patients include the AIDS-defining malignancies [Kaposi’s sarcoma, non-Hodgkin’s lymphoma (NHL), and invasive cervical cancer] and other non-AIDS-defining cancers (Hodgkin’s lymphoma, hepatocellular carcinoma, and lung cancer).4
Due to the complexity and diversity of cancer, the application of personalized medicine in the management of cancer patients has been suggested and encouraged.
Personalized medicine hinges on biomarkers, which are highly sensitive and specific in revealing information that is relevant for diagnosis, prognosis, and therapy.5,6
Thus, biomarker discovery and development are one of the cores of personalized medicine for cancer. Cancer biomarkers may be discovered using molecular, cellular, and imaging methodologies focused on drug and disease mechanisms, thus providing critical feedback about the interaction of novel therapies with their intended target and about the disease itself.7
Biomarkers play a role in cancer screening, early diagnosis, prognosis, cancer stratification, prediction of treatment efficacy, and adverse reaction. A biomarker can consist of genomic and proteomic patterns, single genes or proteins, chromosomal abnormalities, epigenetic signatures, aberrant microRNA (miRNA), as well as imaging changes observed on magnetic resonance imaging (MRI) or positron emission tomography (PET) scan. However, most biomarkers have both prognostic and predictive value.
Biomarker Definition
Biomarkers are characteristics that are objectively measured and evaluated as indicators of normal biological processes, pathogenic processes, and pharmacological responses to a therapeutic intervention.8,9 In cancer, biomarkers are defined as biochemical substances elaborated by cancer cells either due to the cause or effect of malignant process.10
However, cancer biomarkers must be detectable only in the presence of cancer. Cancer biomarkers may be detected in sample matrices such as serum, plasma, whole blood, urine, and tissue.11
They can be normal endogenous products that are produced at a greater rate in cancer cells or the products of newly switched on genes that remained inactive in normal cells. Biomarkers may include intracellular molecules or proteins in tissues or may be released into the circulation and appear in serum, and their presence in significant amount may indicate the presence of cancer.
However, the usefulness of a biomarker lies in its ability to provide early indication of a disease or its progression, and it should be easy to detect and should be measurable across populations.12
