Research Portfolio

Funding Opportunities

Join our Mailing List
Join our mailing list to be notified of new funding opportunities.

Your Email

To receive information about funding opportunities, events, and program updates.

Molecular therapies against small cell lung cancer

Institution: Stanford University
Investigator(s): Jamie Conklin, B.Sc.
Award Cycle: 2009 (Cycle 18) Grant #: 18DT-0006 Award: $60,000
Subject Area: Cancer
Award Type: Dissertation Awards

Initial Award Abstract
The number one cause of cancer related deaths in the United States is lung cancer. Over 80% of lung cancer cases are due to tobacco. Treatments for lung cancer are limited and there is generally a poor survival rate in patients. Small cell lung cancer (SCLC) is a subtype of lung cancer that comprises about 20% of all lung cancer cases and results in over 200,000 deaths worldwide each year. Most people diagnosed with SCLC have a history of heavy smoking, which strongly correlates tobacco use with this cancer. Unfortunately, SCLC has a very poor prognosis, with a 5-year survival rate of less than 5%.

Our goal is to gain a better understanding of the molecular mechanisms underlying the development of SCLC. It is our belief that we might be able to use this knowledge to eventually design new and improved treatment options for this deadly cancer. To do this, we will use SCLC tumor cells obtained from a mouse model: in this model, mice are genetically engineered and manipulated to grow lung cancer that is very similar to human SCLC. This genetically defined system is simpler and more amenable to experimental intervention than tumors in human patients, which will enable us to more easily study the biology of these tumor cells.

Specifically, we propose to re-introduce into these tumor cells lines the two genes, RB and p53, that are most frequently mutated in SCLC. We will determine the effect of re-introducing RB and p53 function on cell growth and survival. Loss of RB and p53 is thought to be an initiating event in SCLC, and we hypothesize that the tumor cells still depend on the loss of function of these two genes to retain their cancer potential. In other words, we hypothesize that re-introducing RB and p53 will stop the tumor cells.

We also will introduce another gene into SCLC cells: K-Ras is usually found altered in other cancer types but rarely in SCLC, and emerging evidence suggests that K-Ras activity may be detrimental to cells with a mutation in RB, such as SCLC cells. Thus, we hypothesize that introduction of K-Ras in SCLC will be incompatible with the molecular changes that have already happened in SCLC cells (loss of RB and p53), which may result in an arrest in tumor cell growth.

It is our hope that the resulting knowledge in this mouse system will enable us to identify novel therapeutic targets that can increase treatment options for patients with SCLC.

Keeping an eye on retinoblastoma control of human embryonic stem cells.
Periodical: Journal of Cellular Biochemistry Index Medicus:
Authors: Conklin JF, Sage J ART
Yr: 2009 Vol: 108 Nbr: 5 Abs: Pg: 1023-1030

Loss of p130 accelerates tumor development in a mouse model for human small-cell lung carcinoma.
Periodical: Cancer Research Index Medicus:
Authors: Schaffer B, Park K, Yiu G, Conklin J, Lin C, Burkhart D, Karnezis A, Sweet-Cordero, Sage ART
Yr: 2010 Vol: Nbr: Abs: Pg: