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\begin{document}

\title{Cancer Research ~ ~~\\}


 \author{The Authorea Team}


\date{}

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\subsubsection*{\texorpdfstring{Main Text\\
}{Main Text }}\label{main-text}

\paragraph{\texorpdfstring{Title Page\\
}{Title Page }}\label{title-page}

\textbf{Title.}~Write a brief, informative title. Abbreviations should
not be used in titles. It is important for literature retrieval to
include in the title the key words that identify the nature of the
subject matter, including, if applicable, the species on which the work
is done.\\

\textbf{Authors and affiliations.}~Authors are urged to include their
full names, complete with first and middle names or initials. Academic
degrees should not be included. The names and locations of institutions
or companies should be given for all authors. Departments, units, or
laboratories should also be specified. If several institutions are
listed on a manuscript, it should be clearly indicated with which
department and institution each author is affiliated by using
corresponding superscript numbers.\\

\textbf{Running title.}~A brief running title of no more than 60
characters should be provided. Choose the running title carefully, as it
will be used in electronic alerting services and some mobile device
applications. Abbreviations may be used in the running title.\\

\textbf{Keywords.}~Provide 5 keywords identifying the subject of the
manuscript.\\

\textbf{Additional information.}~Include the following notes on the
title page (if applicable) in this order:\\

\begin{itemize}
\tightlist
\item
  Financial support, including the source and number of grants, for each
  author\\
\item
  Full name, mailing address, phone and fax numbers, and email address
  of the corresponding author\\
\item
  A conflict of interest disclosure statement; additional information is
  available at this
  link:~\href{http://www.aacrjournals.org/site/InstrAuthors/ifora.xhtml\#coi}{Conflict
  of Interest Policy}\\
\item
  Other notes about the manuscript as a whole, including the word count,
  and the total number of figures and tables Please note that, if you
  substantially exceed the word limit given for the type of article (see
  specific instructions for each journal), your manuscript may be
  returned.\\
\end{itemize}

For~\emph{Clinical Cancer Research}~only, on a page between the title
page and abstract you must provide a 150-word statement of translational
relevance describing how the results might be applied to the future
practice of cancer medicine.\\

\paragraph{\texorpdfstring{Abstract\\
}{Abstract }}\label{abstract}

The abstract must be concise, yet should accurately outline the content
of the manuscript (see the Categories of Articles page of each journal
for abstract length requirements for each type of article). Because
these abstracts are used by secondary services (e.g., MEDLINE, Chemical
Abstracts, Web of Science, Scopus), they should recapitulate in
abbreviated form the purpose of the study and the experimental
technique, results, and data interpretations. Data such as the number of
test subjects and controls, strains of animals or viruses, drug dosages
and routes of administration, tumor yields and latent periods, length of
observation period, and magnitude of activity should be included. Vague,
general statements such as ``The significance of the results is
discussed'' or ``Some physical properties were studied'' should be
avoided. Important terms relevant to the content of the manuscript
should be incorporated into the abstract to assist indexers and
searchers. Abbreviations should be kept to an absolute minimum; however,
if they are needed, they must be explained at first mention within the
abstract so that it can be understood as an independent unit from the
remainder of the manuscript. Do not cite references in the abstract.\\

\paragraph{\texorpdfstring{Introduction\\
}{Introduction }}\label{introduction}

The introduction should provide a brief overview of the background and
rationale for the study. It is not necessary to cite all of the
background literature in the introduction. Brief reference to the most
pertinent articles generally suffices to acquaint the reader with the
findings of others in the field and with the problem or question that
the investigation addresses.\\

\paragraph{\texorpdfstring{Materials and Methods\\
}{Materials and Methods }}\label{materials-and-methods}

Explanation of the experimental methods should be adequate for
repetition by qualified investigators. Procedures that have been
described in previous publications should not be described in detail but
merely cited with appropriate references along with any modifications of
the procedure. Only new and substantial modifications of previously
published procedures need complete exposition. The sources of special
chemicals or preparations used should be provided. Any commercial
products that are mentioned should include the name of the manufacturer
and catalog numbers.\\

\paragraph{\texorpdfstring{Results\\
}{Results }}\label{results}

Include a concise summary of the data presented in all display items
(figures and tables). Excessive elaboration of data shown in display
items should be avoided.\\

\paragraph{\texorpdfstring{Discussion\\
}{Discussion }}\label{discussion}

The data should be interpreted concisely without repeating material
already presented in the Results section. Speculation is permissible,
but it must be well founded, and discussion of the wider implications of
the findings is encouraged.\\

\paragraph{\texorpdfstring{Acknowledgments\\
}{Acknowledgments }}\label{acknowledgments}

Include the names of others contributing to the work who are not
identified as authors.\\

\paragraph{\texorpdfstring{References\\
}{References }}\label{references}

Number the references in the order of their first mention in the text;
cite only the number assigned to the reference. The reference list
should be limited to only those citations essential to the presentation.
Before submission of the manuscript, authors should verify the accuracy
of all references and check that all references have been cited in the
text. The AACR journals' reference style follows that of the Uniform
Requirements for Manuscripts Submitted to Biomedical Journals. For
manuscripts with more than 6 authors, the names of the first 6 authors
must be listed, followed by "\emph{et al.}" For manuscripts with 6 or
fewer authors, all authors should be listed.\\

\textbf{Reference examples:}\\

\textbf{Journal article}\\

Warrell RP Jr, Frankel SR, Miller WH Jr, Scheinberg DA, Itri LM,
Hittelman WN,~\emph{et al.}\\

Differentiation therapy of acute promyelocytic 584 leukemia with
tretinoin (all-trans-retinoic acid).~\emph{N Engl J
Med}\textbf{1991};324:1385--93.~\\

\textbf{Book chapter~}\\

Yuspa SH, Hennings H, Roop D, Strickland J, Greenhalgh DA. Genes and
mechanisms involved in malignant conversion. In: Harris CC, Liotta LA,
editors. Genetic mechanisms in carcinogenesis and tumor progression. New
York: Wiley-Liss; 1990. p.115--26.~\\

\textbf{Article in press}\\

Articles in press may be listed among the references. The author must
provide a DOI to the editor to verify that the article is in press at
the indicated journal.\\

~\\

\subsubsection*{\texorpdfstring{Display Items\\
}{Display Items }}\label{display-items}

\paragraph{\texorpdfstring{Tables\\
}{Tables }}\label{tables}

A summary of the data should be provided in the text with a callout to
the table. Tabular data should not duplicate data already presented in
detail in the text. Unnecessary columns of data that can easily be
derived from other data in the table should not be included. Large
groups of individual values should be avoided; instead, these should be
averaged and an appropriate designation of the dispersion, such as
standard deviation or standard error, should be included. Authors are
obligated to indicate the significance of their observations by
appropriate statistical analysis.\\

Every table must have a descriptive title and enough explanatory
information so the reader can understand the data without reference to
the text. Table titles should be short and to the point and should
generally not include references. Each column must carry an appropriate
heading and, if measurements are given, the units should be given with
the column heading. Number tables using Arabic numerals; table footnotes
should be indicated with lower-case alphabetical letters: a, b, c, etc.
Include a note after the footnotes in which all abbreviations used in
the table that have not been used in the text are explained. Complex or
large tables should be uploaded in a tabular data file format as
supplementary data.\\

Tables should not be included as part of a figure. Authors are
discouraged from submitting tables that have been previously published,
even with permission.\\

\paragraph{\texorpdfstring{Figures\\
}{Figures }}\label{figures}

Figures should be used when salient points need illustration for better
comprehension by the reader. Figures must be submitted in their final
design and color format. All figures that the author intends to have
printed in black and white should be supplied in this format so that
editors and reviewers can properly evaluate the presentation of the
data. For initial submission only, figures may be supplied in pdf, jpg
or Word document format and should be on the same page as the legend,
either at the end of the manuscript file or embedded in the text near
the figure callout.
See~\href{http://www.aacrjournals.org/site/InstrAuthors/ifora.xhtml\#submitfiles}{File
Types}for details on the allowable file types for revised manuscripts.
Figures may only be supplied in pdf or Word document format for initial
submission.\\

Figure legends should briefly describe each figure and the data shown.
Figure legends must include the number of technical and biological
replicates performed for the experiment(s) depicted. Legends should not
repeat details present in the main text and should generally not include
references. Stains and original magnifications should be listed where
applicable. Define all symbols and adequately identify all parts of the
figure necessary for interpretation. Abbreviations explained in the main
text of the manuscript need not be redefined in the figure legend.\\

Figures must be cited and numbered in the order in which they appear in
the text. For revised submissions, all figure legends should be listed
together in one section (Figure Legends) directly preceding the
appearance of the figures in the manuscript. Ensure that both legends
and figures are numbered and match up appropriately.\\

When graphs are reduced to the size of a single column (7.94 cm / 3.125
in), the text in the graph must be no smaller than 6 pt and no larger
than 12 pt, and all symbols must be discernible. In the published form,
the minimum thickness of lines (rules) used to present drawn art is 0.5
point. If a drawn image will be reduced in size for publication, the
lines used to draw the original art must be thick enough to be reduced
and still meet the minimum requirement. Lines thinner than 0.5 point
thickness may be completely lost if an image is reduced in size.\\

Best practices for choice of graph type\\

\begin{itemize}
\tightlist
\item
  Reserve bar charts for presentation of data such as counts and
  lengths.\\
\item
  Use a line graph to display and connect related data points and a bar
  graph for unrelated data points.\\
\item
  Sample data is best displayed by plotting individual data points when
  sample numbers are small. Use a box plot, violin plot, or bean plot
  for larger sample sizes and to show data distributions.
  See\href{http://www.aacrjournals.org/site/InstrAuthors/ifora.xhtml\#statistics}{Statistics}~for
  guidelines on sample sizes. A free tool for plotting sample data and
  generating an EPS file for incorporation into figures is available
  at~\href{http://boxplot.bio.ed.ac.uk/}{http://boxplot.bio.ed.ac.uk}.\\
\item
  A pie chart is effective for showing data trends, but, if it is
  important to provide quantitative comparisons, a bar graph may be
  preferable.\\
\end{itemize}

Best practices for graph design\\

\begin{itemize}
\tightlist
\item
  Avoid the use of patterned fills. These add visual clutter and impede
  interpretation. Use black, up to four shades of gray, and white to
  provide six alternative encodings; or use color if more encodings are
  required.\\
\item
  Always use distinct colors and avoid the use of red and green for
  contrast.\\
\item
  Avoid background shading.\\
\item
  Display only the left and bottom axes unless a top and/or right axis
  is absolutely necessary.\\
\item
  Axes labels should not extend beyond the axes lines and must include
  the name and units of the parameter measured.\\
\item
  Consider whether related data plotted in multiple graphs can and
  should be shown in a single graph.\\
\item
  Remove unnecessary tick marks and grid lines. Use grid lines only when
  necessary and make sure they have substantially less visual prominence
  than the data and axes lines.\\
\item
  Avoid axes breaks. These can mask important differences in the data.\\
\item
  Open symbols, particularly circles, are most appropriate for plotting
  high-density data points that overlap.\\
\end{itemize}

Best practices for images\\

\begin{itemize}
\tightlist
\item
  When images are related to one another or should be compared, group
  them together with narrow bands of white space between them. If the
  image background is close to white, use lines for separation.\\
\item
  Symbols, arrows, letters, and scale bars overlying the image should
  strongly contrast with the background so as to be clearly visible and
  are best provided on a separate layer from the underlying image in a
  layered image file.\\
\item
  Single channel fluorescence images are best displayed in grayscale so
  that intensity differences can be discerned more accurately. Avoid the
  use of red, which is particularly problematic in this regard.\\
\end{itemize}

Figures should be original. Authors are discouraged from submitting
figures that have been previously published, even with permission. If
use of a previously published figure is necessary, the author must apply
for written permission from the copyright holder and supply confirmation
of the permission grant before publication.\\

~\\

\subsubsection*{\texorpdfstring{Supplementary Data\\
}{Supplementary Data }}\label{supplementary-data}

Supplementary data is intended to provide additional substantive
information that is directly relevant to the article content but not
essential for understanding the conclusions. The article must stand on
its own merits and be complete and self-explanatory without the
supplementary data. Additional text, such as supplementary results or
discussion, is not acceptable and should be included in the main
article. Supplementary data should be equal in quality and presentation
to material within the main article. The supplementary data are subject
to the same scientific standards of peer review and are included at the
discretion of the editor. Each supplementary item/file must be
referenced at least once in the main article text at an appropriate
point. Supplementary items should be referred to in a similar manner to
that used for a table or figure in the body of the manuscript, for
example, ``(Supplementary Fig. S1)'' or ``(Table 3 and Supplementary
Table S3).'' Each supplementary file should be accompanied by a brief
description. The description will be posted online to communicate the
contents of the file and to aid in online indexing. Supplementary
figures must include full legends and tables should include captions.\\

General Guidelines on Acceptability\\

\begin{itemize}
\tightlist
\item
  Supplementary data should fall within the conceptual scope of the main
  manuscript but not extend beyond it. Preliminary data that simply
  extend the scope of the study and unnecessary control data should not
  be included.\\
\item
  Supplementary material should not repeat information that is already
  included in the main manuscript.\\
\item
  Data that have been previously published are not acceptable.\\
\item
  Supplementary data may also be that which cannot be included in the
  main version of the manuscript due to space constraints (e.g., limits
  placed on the number of figures and tables allowed in an article) or
  format restrictions.\\
\item
  Within the above guidelines, supplementary files may include the
  following:\\
\item
  Figures and tables\\
\item
  More detailed materials and methods than can be included in the body
  of the article, but the main text should contain sufficient
  methodology for an experienced investigator to replicate the
  experiments\\
\item
  Electronic multimedia files (e.g., video, audio, or animation)\\
\item
  Database information\\
\item
  Three-dimensional structures/images, sequence alignments, and data
  sets that are very large\\
\end{itemize}

Restrictions on number and size of files\\

\begin{itemize}
\tightlist
\item
  The number of supplementary files per article may not exceed 8. In
  special circumstances, an exception may be granted but the author must
  contact the editorial office prior to acceptance.\\
\item
  No individual supplementary data file may exceed 50 MB.\\
\end{itemize}

~\\

\subsubsection*{\texorpdfstring{File Types\\
}{File Types }}\label{file-types}

The following file types are acceptable file formats for the main
manuscript files:\\

\begin{itemize}
\tightlist
\item
  Manuscript files: Word (doc, docx), Encapsulated Postscript (eps),
  Rich Text Format (rtf), or pdf (accepted for initial submissions
  only)\\
\item
  Graphics files: eps, tiff, ai, psd, png, gif or ps. Powerpoint (ppt,
  pptx) files are discouraged but may be acceptable. Color images should
  be supplied in RGB.\\
\end{itemize}

For supplementary data the following file types are acceptable: pdf,
doc, docx, eps, rtf, txt, csv, xls, xlsx, xlsb, xml, avi, mov, mp4, wav,
aiff, mp3 and zip. Other file types may be acceptable but please contact
the journal editorial office.\\

~\\

\subsubsection*{\texorpdfstring{Terminology and Abbreviations\\
}{Terminology and Abbreviations }}\label{terminology-and-abbreviations}

Generic names of drugs are preferred. In order to identify new compounds
that may not be recognized by their generic name, the brand name may be
included at first mention only. If a non-U.S. proprietary name is used,
the name of the comparable U.S. product should be given. When there is
no generic name for a drug, authors should give the chemical name or
formula or a description of the active ingredients. Authors should refer
to the formally adopted generic names listed in the current edition of
USAN and the USP Dictionary of Drug Names.\\

Abbreviations are in general a hindrance to readers in fields other than
that of the author(s), to abstractors, and to scientists whose primary
language is not English. Authors should limit their use. See our brief
list
of~\href{http://www.aacrjournals.org/site/InstrAuthors/standard-abbrev.xhtml}{Standard
Abbreviations}~that may be used without explanation (e.g., DNA). All
abbreviations not on this list must be spelled out at first mention in
both the abstract and the text. Single words (e.g., melanoma, folate,
vincristine) should not be abbreviated, nor should abbreviations be used
for individual types of cancer or other diseases that consist of two
words (e.g., prostate cancer or breast cancer).

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