Introducing CICO: The Consortium for Integrative Computational Oncology

We've had some exciting times in the Macklin Math Cancer Lab!

On May 18th, Paul Newton and I received received significant startup funding from the USC James H. Zumberge Research and Innovation Fund to establish the Consortium for Integrative Computational Oncology (CICO).  We're grateful for this opportunity to build a new resource for USC and the broader cancer community!

CICO seeks to develop and promote cross-disciplinary, integrative collaborations across the USC (particularly the Viterbi School of Engineering and the Keck School of Medicine) in clinically-oriented cancer modeling.  Among our guiding principles:

• Computational modeling of cancer must be driven by clinical needs. Modelers need to work hand-in-hand with clinicians at all steps of the modeling process.
• Computational oncology works at its fullest potential when working with clinical data. This focus:  
• drives advances in mathematical model design, 
• allows us to evaluate and choose between competing models, 
• helps biologists to test, validate, and refine current cancer biology orthodoxy, 
• helps clinicians to better interpret their data, and 
• is most likely to lead to computational tools that will make an impact in the clinic.
• Integrative computational oncology holds the potential to integrate advances from mathematical modeling, experiments, and clinical data into comprehensive tools that give a better understanding of cancer than any of these individual pieces alone.  
• Integrative computational oncology must include student education at its core, to create a true "ecosystem" of clinically-focused modeling students from the undergraduate to postdoctoral level. 

You'll be hearing a lot more about CICO as we ramp up in the coming year!

---

Return to News   Return to MathCancer   Follow @MathCancer

Giving a talk at the PSOC Monthly Seminar

This is a definitely a thrill for me--I'm giving this month's talk at the USC PSOC seminar series. This should be a great opportunity to get the word out on what we're all about. In an unrelated note, be on the lookout for more frequent postings here (including some long promised to my friends in the SMB!)

Here are the talk details:

Date / Time: Friday, May 18, 2012, noon - 1:00 pm

Room / Building: Harkness Auditorium; HSC Clinical Sciences Building, 2nd Floor; 

Address: 2250 Alcazar St., Los Angeles, CA 90033

Lunch: Free pizza at 11:45!

Title: The Emerging Role of Patient-Calibrated Computational Modeling in Cancer Research: A Case Study in Ductal Carcinoma in Situ (DCIS)

Abstract: Current clinical oncology practice can generate a wide variety of data for patients. Radiology is used both to detect and plan surgical excisions. Immunostains performed on pre-surgical biopsies are used to diagnose (and grade) the cancers and select therapeutic agents. Molecular profiling may also help stratify patients and select therapeutic agents. However, there is currently no technique to quantitatively combine these diverse data sources, along with novel in vitro measurements, to improve surgical and therapeutic planning. In this talk, we will discuss efforts by my lab (MathCancer.org) and the Center for Applied Molecular Medicine to solve this issue. We will focus on developing and calibrating biologically-grounded computational models to individual patients (particularly ductal carcinoma in situ), encouraging (and validated!) results in quantitatively predicting clinical progression, the implications for making and quantitatively testing biological hypotheses, and the role of mathematical modeling in facilitating a deeper understanding of biology, pathology, and radiology. We anticipate that such efforts will play an increasing role in driving experimental cell biology, testing and challenging current cancer biology orthodoxy, and ultimately improving clinical care. 

---

Return to News   Return to MathCancer   Follow @MathCancer

Grant submitted to the NSF

Today, Paul Newton and I submitted a joint grant to the National Science Foundation in the Physical and Engineering Sciences in Oncology (PESO) program.  PESO is a neat program jointly run by the NSF and NCI, that has spun off the NCI's recent physical sciences approach to cancer. Our proposal brings together a a variety of techniques (spanning agent-based models, signaling, tissue biomechanics, fluid flow, nonlinear transport, and Markov chains) to study targeted aspects of cancer metastasis, from early microinvasion to circulating tumor cells (CTCs) to whole-body dissemination of metastatic disease.

On a personal note, this is my first proposal as a Co-PI.  *fingers crossed*

---

Return to News   Return to MathCancer   Follow @MathCancer

Giving a talk at USC on Monday, February 6

For those of you in the neighborhood, I'll be giving a on patient-calibrated computational modeling of breast cancer, and on the role of mathematical modeling in facilitating a deeper understanding of pathology and mammography.

Monday, February 6, Center for the Applied Mathematical Sciences (CAMS) at the University of Southern California. 

Link and abstract: http://cams.usc.edu/Colloquia/2-6-2012.html 

---

Return to News   Return to MathCancer

DCIS modeling paper accepted

Recently, I wrote about a major work we submitted to the Journal of Theoretical Biology: "Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS): From microscopic measurements to macroscopic predictions of clinical progression."  

I am pleased to report that our paper has now been accepted.  You can download the accepted preprint here. We also have a lot of supplementary material, including simulation movies, simulation datasets (for 0, 15, 30, adn 45 days of growth), and open source C++ code for postprocessing and visualization.

I discussed the results in detail here, but here's the short version:

1. We use a mechanistic, agent-based model of individual cancer cells growing in a duct. Cells are moved by adhesive and repulsive forces exchanged with other cells and the basement membrane.  Cell phenotype is controlled by stochastic processes.
2. We constrained all parameter expected to be relatively independent of patients by a careful analysis of the experimental biological and clinical literature.
3. We developed the very first patient-specific calibration method, using clinically-accessible pathology.  This is a key point in future patient-tailored predictions and surgical/therapeutic planning. 
4. The model made numerous quantitative predictions, such as: 
1. The tumor grows at a constant rate, between 7 to 10 mm/year. This is right in the middle of the range reported in the clinic. 
2. The tumor's size in mammgraphy is linearly correlated with the post-surgical pathology size.  When we linearly extrapolate our correlation across two orders of magnitude, it goes right through the middle of a cluster of 87 clinical data points.
3. The tumor necrotic core has an age structuring: with oldest, calcified material in the center, and newest, most intact necrotic cells at the outer edge.  
4. The appearance of a "typical" DCIS duct cross-section varies with distance from the leading edge; all types of cross-sections predicted by our model are observed in patient pathology. 
5. The model also gave new insight on the underlying biology of breast cancer, such as: 
1. The split between the viable rim and necrotic core (observed almost universally in pathology) is not just an artifact, but an actual biomechanical effect from fast necrotic cell lysis.
2. The constant rate of tumor growth arises from the biomechanical stress relief provided by lysing necrotic cells. This points to the critical role of intracellular and intra-tumoral water transport in determining the qualitative and quantitative behavior of tumors. 
3. Pyknosis (nuclear degradation in necrotic cells), must occur at a time scale between that of cell lysis (on the order of hours) and cell calcification (on the order of weeks).  
4. The current model cannot explain the full spectrum of calcification types; other biophysics, such as degradation over a long, 1-2 month time scale, must be at play.

I hope you enjoy this article and find it useful. It is our hope that it will help drive our field from qualitative theory towards quantitative, patient-tailored predictions. 

Direct link to the preprint: http://www.mathcancer.org/Publications.php#macklin12_jtb

I want to express my greatest thanks to my co-authors, colleagues, and the editorial staff at the Journal of Theoretical Biology. 

---

Return to News   Return to MathCancer

Now hiring: Postdoctoral Researcher

I just posted a job opportunity for a postdoctoral researcher for computational modeling of breast, prostate, and metastatic cancer, with a heavy emphasis on calibrating (and validating!) to in vitro, in vivo, and clinical data.

If you're a talented computational modeler and have a passion for applying mathematics to make a difference in clinical care, please read the job posting and apply!

(Note: Interested students in the Los Angeles/Orange County area may want to attend my applied math seminar talk at UCI next week to learn more about this work.)

---

Return to News   Return to MathCancer

MMCL welcomes Gianluca D'Antonio

The Macklin Math Cancer Lab is pleased to welcome Gianluca D'Antonio, a M.S. student of Luigi Preziosi and mathematician from Politecnico di Torino. Gianluca, who brings with him a wealth of expertise in biomechanics modeling, will spend 6 months at CAMM at the Keck School of Medicine of USC to model basement membrane deformation by growing tumors, biomechanical feedback between the stroma and growing tumors, and related problems. Gianluca's interests and expertise fit very nicely into our broader vision of mechanistic cancer modeling, as well as USC / CAMM's focus on applying the physical sciences to cancer (as part of the USC-led PSOC).

He is our first international visiting scholar, and we're very excited for the multidisciplinary work we will accomplish together! So, please join us in welcoming Gianluca!

---

Return to News   Return to MathCancer