Intertumoral and Intratumoral Heterogeneity of Cancer: Types, Causes, Detection, and Clinical Implications Open Access

Abstract

Intertumoral and intratumoral heterogeneity of cancers pose significant challenges to the development of effective antineoplastic therapies. Tumors contain a complex admixture of different clonal populations, each of which may vary in their mechanisms of proliferation and maintenance. The latest technology developments in the genomic and proteomic areas further define tumor heterogeneity at the molecular level, making it feasible to develop personalized treatment approaches. This review will highlight the types of heterogeneity, the ways in which heterogeneity arises, and how heterogeneity can be evaluated. Further, this review will explore current and emerging immunotherapies and personalized treatment strategies to best overcome tumor heterogeneity.

Table of Contents

Introduction…………………………………………………………………………………….........…..1

I.              Types of Cancer Heterogeneity………………………………………………………..2-22

Figure 1. The different levels of tumor heterogeneity…………………………..2-3

Genetic Heterogeneity…………………………………………………………..........3-7

Transcriptional Heterogeneity…………………………………………………........7-8

Epigenetic Heterogeneity……………………………………………………..........9-11

Cellular Tumor Microenvironmental Heterogeneity……………………….…11-18

Spatial and Structural Heterogeneity……………………………………….......19-20

Metastatic Heterogeneity…………………………………………………….........20-22

Macroenvironmental Heterogeneity…………………………………………….......22

II.            Causes of Tumor Heterogeneity……………………………………………………..22-28

Figure 2. Clonal Evolution and Cancer Stem Cell Hypotheses………………….23

Clonal Evolution Hypothesis……………………………………………………........24

Cancer Stem Cell Hypothesis……………………………………………….........24-25

Other Hypothesized Models of Tumor Evolution……………………………..25-27

Genomic Instability…………………………………………………………..........27-28

III.          Methods for Evaluating Heterogeneity……………………………………………..29-33

Tumor Heterogeneity Algorithms……………………………………………….......29

Invasive Sampling Approaches………………………………………………......29-31

Non-Invasive and Minimally Invasive Approaches…………………………..31-33

IV.         Therapeutic Approaches to Overcome Heterogeneity…………………………...33-41

Synthetic Lethality……………………………………………………………........33-34

Limitations of Target Therapies…………………………………………….......34-35

Immune Checkpoint Inhibitors……………………………………………….....…..35

Whole Cell and Membrane-Based Vaccines………………………………...…36-37

Dendritic Cell Vaccines…………………………………………………........……37-38

Adoptive Cell Transfer……………………………………………………........….38-40

Oncolytic Viruses……………………………………………………………..........40-41

Conclusion..........................................................................................................41-42

Works Cited.........................................................................................................43-61

About this Honors Thesis

Rights statement

• Permission granted by the author to include this thesis or dissertation in this repository. All rights reserved by the author. Please contact the author for information regarding the reproduction and use of this thesis or dissertation.

School	Emory College
Department	Biology
Degree	B.S.
Submission	Honors Thesis
Language	English
Research Field	Health Sciences, Immunology Biology, Cell Biology, Genetics
Keyword	Cancer Genomics Immunotherapy
Committee Chair / Thesis Advisor	Selvaraj, Periasamy, Emory University
Committee Members	Abreu, Eladio, Emory University Salaita, Khalid, Emory University Munoz, Luis, Emory University Bommireddy, Ramireddy, Emory University

Last modified

Primary PDF

Thumbnail	Title	Date Uploaded	Actions
	Intertumoral and Intratumoral Heterogeneity of Cancer: Types, Causes, Detection, and Clinical Implications ()	2020-12-08 10:05:37 -0500	Press to Select an action Download

Supplemental Files

Thumbnail	Title	Date Uploaded	Actions