Santa Fe Institute Events Wiki - User contributions [en]

Neoplasms amenable to somatic evolutionary studies

2008-06-12T02:04:03Z

Cmaley: /* What we can study today in human neoplasms */

==Premalignant conditions we can study longitudinally==
===Animal carcinogen models===
* mouse skin
* rat Barrett’s esophagus
* mouse colonoscope for colorectal cancer
Measure:
* rate of progression
* time to relapse
* manipulate the rate of progression
* similarity of adaptive landscapes across tumors
* parallel between mouse and human adaptive landscape

===What we can study today in human neoplasms===
* hematopoietic (blood samples)
* bladder (urine samples)
* lung cancer (fiberoptics, sputum, spiral CT)
* Barrett’s esophagus
* Gastric pre-malignant lesions
* Oral cavity (oral leukoplakia)
* breast (DCIS studies, some people may leave it in)
* Prostate (elevated PSA may trigger multiple biopsies)
* Ulcerative colitis

===Premalignant systems that will take significant workup===
What we can do tomorrow (minimal changes to standard of care)
* GI (fecal samples? may take assay development)
* Squamous esophagus (in China or other places)
* cervical (serial pap smears? issue of potential malpractice if lesion was missed)

===What we can do 5+ years from now (more significant changes)===
* Skin
** hard because it is often completely removed
** may be able to look at surrounding tissue (check normal margins on resection to see if genetic abnormality)
** We may be able to convince clinicians to check adjacent tissue if we can justify it

== Malignancies (to study resistance to therapy) ==
===What we can do today (not a complete or accurate list)===
*Hematopoietic neoplasms
*Bladder
*Oral cancer
*Lung has been done to study resistance
*Prostate
*Colon (with liver metastases)
*Brain cancers (serial debulking? Imaging is very common) - Sidransky?
*melanoma with metastases
** dermatologists are not usually involved in cancer research, which is a problem
** may not include biopsies of mets
*childhood cancers and second tumors later - long follow-up (UNM, Penn)
*Anything where we can get before/after tissue samples or sample before treatment and tumor growth dynamics (or other measures) after treatment

Integrating Evolutionary Theory into Cancer Biology

2008-05-25T20:37:27Z

Cmaley:

Pages for use during the meeting:

{{Integrating Evolutionary Theory into Cancer Biology}}

== Meeting Notes ==
* [[ meeting notes by John P.]]
* [[May 20 Notes]]

== Results of Discussions ==
[[Sources of therapeutic failure]]

[[Important Clinical Questions in Cancer Biology]]

[[Neoplasms amenable to somatic evolutionary studies]]

Integrating Evolutionary Theory into Cancer Biology - Background Papers

2008-05-25T20:34:24Z

Cmaley:

{{Integrating Evolutionary Theory into Cancer Biology}}

A link to Rafe Furst's blog: "Cancer Research Surprises"
http://rafefurst.wordpress.com/2008/04/10/cancer-research-surprises/

Click on the citations below to download a PDF file:

[[Media:Crespi_&_Summers_2005.pdf|Crespi, B. and K. Summers 2005. Evolutionary biology of cancer. Trends in Ecology & Evolution 20(10): 545-552.]] 

[[Media:Galipeau-PLoS-med-4-e67.pdf|Galipeau, P.C., X. Li , P.L. Blount, C.C. Maley, C.A. Sanchez, R.D. Odze, K. Ayub, P.S. Rabinovitch, T.V. Vaughan, B.J. Reid. 2007. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Medicine. 4(2):e67]] 

[[Media:Gatenby_&_Vincent_2003.pdf|Gatenby, R. A. and T. L. Vincent 2003. An evolutionary model of carcinogenesis. Cancer Research 63(19): 6212-6220.]] 

[[Media:Hanahan_&_Weinberg_2000.pdf|Hanahan, D. and R. A. Weinberg. 2000. The hallmarks of cancer. Cell 100(1): 57-70.]] 

[[Media:Nat-gen-38-468.pdf|Maley, C.C., P.C. Galipeau, J.C. Finley, V.J. Wongsurawat, X. Li, C.A. Sanchez, T.G. Paulson, P.L. Blount, R. Risques, P.S. Rabinovitch, and B.J. Reid. 2006. Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nature Genetics, 38:468–473.]] 

[[Media:Maley_&_Reid_2005.pdf|Maley, C. C. and B. J. Reid 2005. Natural selection in neoplastic progression of Barrett's esophagus. Seminars in Cancer Biology 15(6): 474-483.]] 

[[Media:Merlo_Pepper_et_al_2006_NRC.pdf|Merlo, L.M.F., Pepper, J.W., Reid, B.J., and Maley, C.C. 2006. Cancer as an evolutionary and ecological process. Nature Reviews Cancer. 6: 924-935.]] 

[[Media:Spencer_et_al_2006.pdf|Spencer, S. L., R. A. Gerety, K.J. Pienta, and S. Forrest. 2006. Modeling somatic evolution in tumorigenesis. Plos Computational Biology 2: 939-947.]] 

[[Media:Vincent_&_Gatenby_2008.pdf|Vincent, T. L. and R. A. Gatenby (2008). "An evolutionary model for initiation, promotion, and progression in carcinogenesis. International Journal of Oncology 32(4): 729-737.]]

File:Nat-gen-38-468.pdf

2008-05-25T20:32:04Z

Cmaley:

File:Galipeau-PLoS-med-4-e67.pdf

2008-05-25T20:31:29Z

Cmaley:

Integrating Evolutionary Theory into Cancer Biology - Background Papers

2008-05-25T20:31:15Z

Cmaley:

{{Integrating Evolutionary Theory into Cancer Biology}}

A link to Rafe Furst's blog: "Cancer Research Surprises"
http://rafefurst.wordpress.com/2008/04/10/cancer-research-surprises/

Click on the citations below to download a PDF file:

[[Media:Crespi_&_Summers_2005.pdf|Crespi, B. and K. Summers 2005. Evolutionary biology of cancer. Trends in Ecology & Evolution 20(10): 545-552.]] 

[[Media:Galipeau-PLoS-med-4-e67.pdf|Galipeau, P.C., X. Li , P.L. Blount, C.C. Maley, C.A. Sanchez, R.D. Odze, K. Ayub, P.S. Rabinovitch, T.V. Vaughan, B.J. Reid. 2007. NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Medicine. 4(2):e67]] 

[[Media:Gatenby_&_Vincent_2003.pdf|Gatenby, R. A. and T. L. Vincent 2003. An evolutionary model of carcinogenesis. Cancer Research 63(19): 6212-6220.]] 

[[Media:Hanahan_&_Weinberg_2000.pdf|Hanahan, D. and R. A. Weinberg. 2000. The hallmarks of cancer. Cell 100(1): 57-70.]] 

[[Media:Maley_&_Reid_2005.pdf|Maley, C. C. and B. J. Reid 2005. Natural selection in neoplastic progression of Barrett's esophagus. Seminars in Cancer Biology 15(6): 474-483.]] 

[[Media:Merlo_Pepper_et_al_2006_NRC.pdf|Merlo, L.M.F., Pepper, J.W., Reid, B.J., and Maley, C.C. 2006. Cancer as an evolutionary and ecological process. Nature Reviews Cancer. 6: 924-935.]] 

[[Media:Spencer_et_al_2006.pdf|Spencer, S. L., R. A. Gerety, K.J. Pienta, and S. Forrest. 2006. Modeling somatic evolution in tumorigenesis. Plos Computational Biology 2: 939-947.]] 

[[Media:Vincent_&_Gatenby_2008.pdf|Vincent, T. L. and R. A. Gatenby (2008). "An evolutionary model for initiation, promotion, and progression in carcinogenesis. International Journal of Oncology 32(4): 729-737.]]

Neoplasms amenable to somatic evolutionary studies

2008-05-24T05:37:31Z

Cmaley:

==Premalignant conditions we can study longitudinally==
===Animal carcinogen models===
* mouse skin
* rat Barrett’s esophagus
* mouse colonoscope for colorectal cancer
Measure:
* rate of progression
* time to relapse
* manipulate the rate of progression
* similarity of adaptive landscapes across tumors
* parallel between mouse and human adaptive landscape

===What we can study today in human neoplasms===
* hematopoietic (blood samples)
* bladder (urine samples)
* lung cancer (fiberoptics, sputum, spiral CT)
* Barrett’s esophagus
* Gastric pre-malignant lesions
* Oral cavity (oral leukoplakia)
* breast (DCIS studies, some people may leave it in)
* Prostate (elevated PSA may trigger multiple biopsies)
* Ulcerativ colitis

===Premalignant systems that will take significant workup===
What we can do tomorrow (minimal changes to standard of care)
* GI (fecal samples? may take assay development)
* Squamous esophagus (in China or other places)
* cervical (serial pap smears? issue of potential malpractice if lesion was missed)

===What we can do 5+ years from now (more significant changes)===
* Skin
** hard because it is often completely removed
** may be able to look at surrounding tissue (check normal margins on resection to see if genetic abnormality)
** We may be able to convince clinicians to check adjacent tissue if we can justify it

== Malignancies (to study resistance to therapy) ==
===What we can do today (not a complete or accurate list)===
*Hematopoietic neoplasms
*Bladder
*Oral cancer
*Lung has been done to study resistance
*Prostate
*Colon (with liver metastases)
*Brain cancers (serial debulking? Imaging is very common) - Sidransky?
*melanoma with metastases
** dermatologists are not usually involved in cancer research, which is a problem
** may not include biopsies of mets
*childhood cancers and second tumors later - long follow-up (UNM, Penn)
*Anything where we can get before/after tissue samples or sample before treatment and tumor growth dynamics (or other measures) after treatment

Integrating Evolutionary Theory into Cancer Biology

2008-05-24T05:29:26Z

Cmaley:

Pages for use during the meeting:

{{Integrating Evolutionary Theory into Cancer Biology}}

[[ meeting notes by John P.]]

[[May 20 Notes]]

[[Sources of therapeutic failure]]

[[Important Clinical Questions in Cancer Biology]]

[[Neoplasms amenable to somatic evolutionary studies]]

Important Clinical Questions in Cancer Biology

2008-05-24T05:26:41Z

Cmaley:

The most important, and overarching question is:
=== How can we increase survival? ===
It is not enough to reduce cancer, if our interventions cause more deaths than the cancer would. Thus, the most important outcome is all cause mortality. But, in order to improve all cause mortality, vis a vis cancer, there are many important clincial questions. '''Those most likely to be informed by understanding somatic evolution are highlighted in bold.'''
* When should we intervene (risk stratification)?
** Applies to both pre-cancer and cancer
** '''Who is likely to progress to cancer?'''
** '''Who is unlikely to progress and can be reassured and removed from the medical system?'''
** Who should get which interventions?
** Who should we screen (who has dangerous somatic evolution)?
* When to stop or change treatment?
* '''How can we delay malignancy?'''
* How can we increase cancer survival?
** This does not necessarily require killing cancer cells, though that tends to be people's default approach
** '''How can we delay the emergence of therapeutic resistance?'''
*** This can be cast as an optimization problem
*** Identify patients likely to be resistant
*** What modalities should be used for treatment (which are best for somatic evolution and how do we get synergy)?
**** Agents, Immune, Lifestyle, Devices, Radiation, Gene Therapy
**** How can we develop new modalities?
** What should we target?
** Who should get which interventions?
** How can we reduce the toxicity of our interventions?
* How do we get solutions into a clinic?
** Somatic evolution doesn't have much to say about this.
* How can we reduce the costs and stress of cancer management?
** Somatic evolution doesn't have much to say about this.

Integrating Evolutionary Theory into Cancer Biology

2008-05-24T05:14:00Z

Cmaley:

Sources of therapeutic failure

2008-05-22T04:57:41Z

Cmaley:

The field of cancer drug resistance is pretty diverse, with causes ascribed to:
* Hypoxia
** if oxygen can't get to the cells, drugs might not either
** Oxygen is necessary for radiotherapy response
* Lack of the drug target (e.g., ER- cells in tamoxifen therapy)
* Density of the microenvironment - neoplasms and their surrounding matrix are often dense, and may impede drug diffusion.
* Upregulation of eflux pumps
* Methylation changes (not sure which yet)
* Genetic changes:
** Gleevec (Imatinib): BCR-ABL mutations
** 5-Flurouracil: TYMS amplification
** Gefitinib:
*** EGFR mutation
*** MET amplification
** Anti-angiogenic therapy
*** Switching expression to a new angiogenic factor not targeted by the drug
*** Growth along existing blood vessels
** Tamoxifen (and other selective estrogen modulating drugs)
*** Loss of the estrogen receptor (domination by a clone that does not require ER)
*** Upregulation of the estrogen receptor
*** Constitutive activation of the estrogen receptor (rare in clinical samples)
*** Mutant, hypersensitive ER

Sources of therapeutic failure

2008-05-22T04:51:30Z

Cmaley:

The field of cancer drug resistance is pretty diverse, with causes ascribed to:
* Hypoxia
** if oxygen can't get to the cells, drugs might not either
** Oxygen is necessary for radiotherapy response
* Lack of the drug target (e.g., ER- cells in tamoxifen therapy)
* Density of the microenvironment - neoplasms and their surrounding matrix are often dense, and may impede drug diffusion.
* Upregulation of eflux pumps
* Methylation changes (not sure which yet)
* Genetic changes:
** Gleevec (Imatinib): BCR-ABL mutations
** 5-Flurouracil: TYMS amplification
** Gefitinib:
*** EGFR mutation
*** MET amplification
** Tamoxifen (and other selective estrogen modulating drugs)
*** Loss of the estrogen receptor (domination by a clone that does not require ER)
*** Upregulation of the estrogen receptor
*** Constitutive activation of the estrogen receptor (rare in clinical samples)
*** Mutant, hypersensitive ER

Integrating Evolutionary Theory into Cancer Biology

2008-05-22T04:25:05Z

Cmaley:

Pages for use during the meeting:

{{Integrating Evolutionary Theory into Cancer Biology}}

[[ meeting notes by John P.]]

[[May 20 Notes]]

[[Sources of therapeutic failure]]

Integrating Evolutionary Theory into Cancer Biology - Participants

2008-05-20T03:57:21Z

Cmaley:

{{Integrating Evolutionary Theory into Cancer Biology}}

=== Attendees ===
Stephanie Forrest, University of New Mexico & Santa Fe Institute 
Henry Heng, Wayne State University School of Medicine 
David Krakauer, Santa Fe Institute 
Carlo C. Maley, The Wistar Institute 
John Pepper, University of Arizona & Santa Fe Institute 
Brian J. Reid, Fred Hutchinson Cancer Research Center 
Sabrina Spencer, MIT 
Thomas L. Vincent, Aerospace and Mechanical Engineering - University of Arizona 

=== Unable to Attend ===
Bernard Crespi, Simon Fraser University 
Robert A. Gatenby, University Medical Center - University of Arizona 
Ricard Sole, Santa Fe Institute 
Michael Tracy, Mayo Clinic - ASU Center for Cancer-Related Convergence, Cooperation and Collaboration

Integrating Evolutionary Theory into Cancer Biology

2008-05-20T03:55:41Z

Cmaley:

Pages for use during the meeting:

{{Integrating Evolutionary Theory into Cancer Biology}}

[[ meeting notes by John P.]]