Shifting Trends in Oncology

Drug-development companies and contract research organizations (CROs) are now recognizing a growing need to screen drug candidates in early stage development. Oncology, as with other areas of drug discovery, is a field that is shifting rapidly. So what is hot in oncology today, and what trends and focus areas can we expect moving forward? Are oncological researchers still investigating and discussing the same trends they were looking at in 2013?

To provide accurate forecasts on potential oncological trends and focus areas, it is often useful to look back at the previous year. Crown Bioscience analyzed all presentations and publications at the American Association for Cancer Research (AACR) and the European Organization for Research and Treatment of Cancer (EORTC) Molecular Targets and Cancer Therapeutics conferences, together with AACR’s annual meetings, since 2011. The results were unexpected.

Trends in 2013
The first keyword group to be analyzed comprised main solid cancer types and the relative frequency with which they were mentioned in 2013. These can be seen below in Table I.

Table I: The relative frequency of keywords between the main solid cancer types in 2013.

AACR(Relative % frequency)

EORTC(Relative % frequency)

Breast

23%

19%

Brain

6%

5%

Colon/colorectal

11%

15%

Head & neck

5%

3%

Liver

6%

4%

Lung

15%

18%

Melanoma

8%

11%

Ovarian

7%

7%

Pancreatic

6%

7%

Prostate

10%

7%

Renal

3%

4%

By comparing these with the results in Table II, it is possible to identify any significant change in focus between the main solid tumor cancer areas.

Table II: The change in frequency of keywords in solid cancer types between 2011 and 2013.

AACR(Relative % frequency)

EORTC(Relative % frequency)

Breast

0%

0%

Brain

-1%

-2%

Colon/colorectal

-1%

2%

Head & neck

1%

-1%

Liver

0%

-1%

Lung

1%

2%

Melanoma

1%

1%

Ovarian

0%

0%

Pancreatic

0%

0%

Prostate

0%

-4%

Renal

0%

-1%

There is no specific evidence of any significant changes in the frequency of publications associated with the listed cancer types, and while the dip in the 2013 EORTC prostate percentage stands out in comparison to previous years, it is most likely an anomaly.

The second word group to be analyzed comprised hematological cancer types. The results are shown below in Table III.

Table III: The relative frequency of keywords between the hematological cancer types in 2013.

AACR
(Relative % frequency)

EORTC
(Relative % frequency)

Acute lymphocytic lymphoma (ALL)

33%

39%

Acute myeloid leukemia (AML)

26%

21%

Chronic myelogenous leukemia (CML)

13%

6%

Non-Hodgkins lymphoma (NHL)

7%

3%

Multiple myeloma (MM)

21%

31%

Table IV shows the frequency fluctuation of keywords between 2011 and 2013, as a percentage of the overall number of presentations each year.

Table IV: The change in frequency of keywords in hematological cancer types between 2011 and 2013.

Cancer type

AACR
(Relative % frequency)

EORTC
(Relative % frequency)

Acute lymphocytic lymphoma (ALL)

-7%

3%

Acute myeloid leukemia (AML)

9%

4%

Chronic myelogenous leukemia (CML)

6%

-5%

Non-Hodgkins lymphoma (NHL)

-3%

-1%

Multiple myeloma (MM)

-5%

0%

Considering the low frequency associated with hematological keywords, there is no significant change in numbers, and research will continue to compare these figures with data collected through 2014.

Thus far, the analysis of both keyword groups does not indicate any radical shifts in research areas of interest. However, on analysis of frequency of term usage relating to informal feedback from scientific and business development teams, some important trends can be observed.

Resistance, epithelial-mesenchymal transition (EMT) and tumor microenvironment
2013 saw the popular discussion of cancer resistance, which became a particularly common theme in terms of both the mechanisms of resistance and pharmacological approaches to overcome them. Over the past two years, the discussion of resistance at AACR has increased in popularity by 22%, while the terms “tumor microenvironment” and “EMT” have increased by 19%. Contrary to expectation, mention of immunotherapy has not increased during this time despite its appearance in many articles citing its importance. The fact that many of these results are not reflected in recent research publications might indicate that publication figures cannot be equated with early drug discovery.

There were several noticeable exceptions uncovered when the 40+ other terms and references to key mutations were reviewed, but the majority of terms and reference to their use remained unpredictably constant. The term “patient xenograft models,” however, stands out above all other terms and references analyzed.

Patient-derived xenograft models (PDX)
The use of patient-derived xenograft (PDX) models became mainstream in drug development and discovery in 2013, and the seven-fold increase in references at AACR since 2011, and nine-fold increase at the EORTC, attest to their use in research and drug-discovery platforms.

PDX models are derived directly from human cancers, with primary tumor cells grafted directly from the patient and sustained either in vitro or in vivo for clinical testing. By keeping models in passage, drug discovery companies are presented with opportunities for treatment regimen screening and to run Phase II-type trials using PDX as human surrogate models. These models provide a higher level of confidence for decision making on drug candidates, which not only provide deep biological insights into the pharmacological mechanisms of a drug, but also help to identify potential biomarkers important to clinical trial design.

What lies ahead for 2014?
The push to increase clinical understanding has led to increasing dependence upon PDX models and human surrogate trials, while research advancements have given birth to new therapies such as image-guided irradiation. One of the most exciting trends to emerge this year, image guided irradiation produces a concentrated and targeted treatment for cancer. Used in conjunction with a PDX model preclinical trial, this method closely mimics contemporary human disease and current treatment regimens, thus enabling higher throughput evaluations of potential radiation synthesizers.

It is becoming clear that the future of oncological research and development is in personalized medicine and the exploration of uniquely tailored therapeutics to combat the wide diversity of cancer subtypes. While no single treatment is effective across the cancer spectrum for all patients even within a single cancer type or subtype, the use of PDX models will allow drug discovery and development companies to make better informed decisions, thereby accelerating only their most effective candidates into the clinic.

Jean Pierre Wery is president of Crown Bioscience, www.crownbio.com