The Promise of Single Cell Omics for Onco-therapy

Abstract

Despite extensive research effort and considerable progress, the "war on cancer" that president Nixon declared in 1971 has yet to be optimally integrated into cancer therapeutics and as such cancer remains a major medical challenge for oncologists. The dynamic and complex biology of tumor cells undergoing clonal evolution generates cells with diverse degrees of drug resistance and metastatic potential. This highlights the need to be able to access this clonal density in order to develop effective therapeutics. With this prospective, early phase single cell studies are vital for thoroughly interrogating tumor heterogeneity to uncover more about cancer cell biology and to explore new therapeutic targets leading to more successful treatments. Current evidence supports the notion that clonogenic cells within the tumor mass may potentially give rise to a population of cells with unique genomic, transcriptomic and proteomic features distinct from the rest of the tumor mass. This observation can explain drug resistance after an initial period of primary tumor response. Therefore, completely abrogating or at a minimum achieving long-term, durable control over cancer requires researchers and oncologists to employ a personalized medicine approach that includes both tumor and patient-associated variables to modify current therapeutic regimens. In this review we discuss the importance of omics and in particular single cell genomics which are increasingly promising given recently developed technology advancements to facilitate exploration of cellular heterogeneity and tumor complexity. Keywords: Cancer genomics; Single cell; Tumor heterogeneity; Oncology therapy The Combinatorial Nature of CancerCancer is a catch all term for a collection of many related, but discrete diseases that share some degree of commonality, but can no longer be considered a single disease [1]. Although tumors may initiate following malignant transformation of even a single normal cell, more probably continuous genetic mutations and gene expression alterations during tumor progression lead to a metastatic phenotype composed of multiple subsets of tumor cells with distinct characteristics. In fact, each of the genetic and epigenetic events that happen to the tumor cells after tumor initiation result in a disease that collectively is termed cancer. Yet each discrete cancer shares certain characteristics with other malignancies. In this context, malignancy of tumor cells increase as a result of the cumulative formation of a series of tumor clones. Multi-step Cancer DevelopmentThe six elements of the model of multi-step cancer development [2] including uncontrolled proliferation, growth suppressor inactivation, cell death resistance, replicative immortality, angiogenesis induction and acquisition of an invasive and metastatic phenotype should be considered when defining a novel therapeutic regimen to eradicate primary and metastatic disease. Furthermore, these elements are important considerations for successful cancer therapy in the context propo...

High-throughput sequencing in clinical oncology: from past to present

“…Unravelling cancer's complexity by harnessing the power of cutting-edge technologies and computing tools has become a major objective of cancer research [3]. To this end, whole-genome sequencing and new measurement technologies let us pinpoint new therapeutic attack strategies [4]. The detection of alterations in gene-based structure and function could have major consequences for the diagnosis, prognosis and treatment of cancer [5].…”