Small cell lung cancer (SCLC)

Immunotherapy

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Lung cancer Equity Through Social needs Screening (LETS SCREEN)

2022

Health Equity and Inclusiveness Junior Investigator Award

Ana Velazquez Manana, MD

University of California, San Francisco

San Francisco

Dr. Velasquez Manana will conduct an observational study in a multiethnic group of patients with unresectable lung cancer to determine the association between social needs, care utilization, and quality of life. The goal of this study is to fill a key knowledge gap in the care of patients with NSCLC and inform interventions to support patients at risk of social adversity during treatment to end disparities in lung cancer care.

Research Summary

Social circumstances in which we are born and live are some of the most important factors influencing our health. For people with cancer, these social circumstances (social determinants of health) drive differences in access to cancer screening and diagnostic tests, stage at diagnosis, and the types of treatments they are offered and receive. The treatment options for people living with lung cancer have changed drastically over the last decade with the addition of immunotherapies and targeted drugs. However, these treatments are not accessible to all. The high costs of cancer treatments and time lost from work make people with cancer more vulnerable to financial hardship, that could affect their ability to receive cancer treatments. In this study, we hope to understand how social needs (e.g., food access, ability to pay bills, access to transportation, housing stability, social isolation, and loneliness) relate to the use of healthcare, quality of care patients with lung cancer receive, and quality of life during their treatment. To do this, we will survey 150 patients with unresectable lung cancer within one month of start of systemic treatment and at 3 and 6-months during their treatment. We will measure how social needs change over time and relate to the use of healthcare for acute problems (i.e., emergency room visits, admissions to the hospital, and urgent care visits), quality of life, and quality of care received. To obtain an in-depth understanding of how social needs can affect patient care, we will interview 30 oncology providers. Providers will be asked if and how they consider the social needs of their patients when making treatment and clinical decisions. This study will give us essential information on how to better support patients with lung cancer who face social needs that impact their daily lives and cancer care.

Technical Abstract

Despite significant progress in the development of novel biomarkers and therapies for lung cancer, such progress has not equitably benefitted all population groups in the United States (US). Racial and ethnic minorities, low income, uninsured, and underinsured individuals with non-small cell lung cancer (NSCLC) continue to experience disparate access to diagnostics tests and treatments, and experience inferior outcomes. These disparities are, at least, partially driven by social context (i.e., social determinants of health). Patients with NSCLC experience high rates of financial hardship and unmet supportive needs, making them a population likely to have high rates of health-related social needs. The prevalence of social needs in patients with NSCLC and their impact on healthcare utilization, cancer outcomes, and quality of life (QOL) remains unknown. To fill this important knowledge gap, we propose an observational, prospective cohort study of 150 patients with unresectable lung cancer receiving first-line systemic therapy. Our study has two primary goals (Aims): 1) Prospectively quantify the prevalence of social needs and determine the associations between social needs, acute care utilization, and QOL; 2) investigate how patient’s social needs influence oncology providers’ clinical decisions for outpatient cancer care of adults with unresectable NSCLC. To achieve these goals, we will conduct serial survey assessments of 150 patients with unresectable NSCLC and conduct semi-structured interviews with 30 oncology providers. This study is significant as it is the first study longitudinally evaluating social needs during cancer therapy in patients with NSCLC. This study will fill a key knowledge gap and inform interventions focused on identifying and supporting patients at risk of social adversity during cancer treatment.

Key words

Health equity

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Young lung cancer: psychosocial needs assessment

2022

Health Equity and Inclusiveness Junior Investigator Award

Narjust Florez, MD

Dana-Farber Cancer Institute

Boston

Dr. Florez will study the psychosocial and financial impact of lung cancer in young patients (< 50 years of age). This patient population has seen an increase in incidence in recent years, but little is known about their specific needs. The study will include administration of a survey and focus groups to understand unmet needs of this group of patients. The information gathered from this study will be used to identify challenges unique to this population and develop the first clinical and research program of its kind for young lung cancer patients.

Research Summary

The number of lung cancer cases in young patients (<50 years of age) is increasing across the globe, from Asia to the United States. Young patients with lung cancer are more likely to be women, of Hispanic or Asian descent and be diagnosed with metastatic disease. In this patient population, a lung cancer diagnosis is not age normative and is profoundly disruptive. Young patients often receive more aggressive treatments and face long-term side effects. While we have seen substantial progress in mental health research in recent years, little is known about the psychological needs of young patients with lung cancer, including how they compare to those of older patients, the financial toxicity associated with their cancer treatments, and how their experiences with the healthcare system impact their wellbeing. Most survivorship studies in lung cancer have included small numbers of young patients with lung cancer, with many of these studies preceding newer cancer treatments like targeted therapy and immunotherapy.

We proposed a mixed-method study that will be designed in conjunction with an experienced research team and lung cancer patient advocates. The study will be divided into two phases 1) we plan to administer a survey that explores the psychosocial needs and the financial impact of cancer treatments to a group of young and old patients with lung cancer; this survey could be completed online, in person, or over the phone with trained personnel 2) following the survey completion, information from the survey will be used to create a guide for focus group discussions; we will conduct four focus groups with young patients with lung cancer to expand on the knowledge obtained from the survey. Focus groups are a powerful way to gain a comprehensive understanding of patient experiences by interacting on a personal, exploratory level to hear patient voices and understand their needs. We will also investigate the differences in these needs by gender and race/ethnicity in our two groups. The study results will be shared with the lung cancer patient community via a series of webinars.

The knowledge obtained from this study will be used to create the first clinical program dedicated to young patients with lung cancer in the nation and the creation of an international consortium that will focus on understanding why the number of lung cancer cases is increasing in patients <50 years of age. Most importantly, we will use the information to create interventions to improve this vulnerable population's clinical care and psychosocial support. Our study will be the first of its kind to critically evaluate the psychosocial needs of young patients with lung cancer in a diverse patient population with a secondary focus on their experiences with the healthcare system and the financial impact of a cancer diagnosis and treatments.

Technical Abstract

Background: In recent years, an increasing incidence of lung cancer among young patients (<50 years) has been reported in Europe, Asia, and the United States. Young patients with lung cancer are more likely to be women, of Asian or Hispanic descent, have adenocarcinoma histology, and are more likely to present with distant metastases at diagnosis. Although young patients with lung cancer are more likely to be diagnosed at a disruptive time in their lives and face greater mental health and financial challenges than older patients with lung cancer, we lack data regarding their specific psychosocial needs. The lack of inclusion of young patients in survivorship studies has created a knowledge gap that we propose to remedy with the proposed study.

Aim and Hypothesis: The overarching aim of this study is to define the psychosocial needs of young patients with lung cancer and evaluate important cancer care delivery factors, including financial toxicity, gender and racial differences and study participants’ experiences with the healthcare system. We hypothesize that young patients will have greater unmet psychosocial needs and financial toxicity than older patients with lung cancer.

Methods: This study will utilize an expert, multi-disciplinary research team aligned with patient advocates to deploy an explanatory sequential mixed methods design to understand the needs of young patients with lung cancer. We will conduct a cross-sectional two-arm survey regarding psychosocial distress and financial toxicity among a diverse patient population utilizing two validated questionnaires, the Psychosocial Screen for Cancer (PSSCAN-R) questionnaire and the COmprehensive Score for financial Toxicity (COST) assessment. After the quantitative data collection is completed, we will conduct a preliminary analysis that will guide the discussion in the next phase, where we will conduct four focus groups with young patients with lung cancer to expand and obtain in-depth answers about the issues discovered in the survey portion of the study. The study team will collaborate with experienced biostatisticians and qualitative data researchers to conduct the appropriate statistical analysis.

Results and Dissemination Plan: The study results will be submitted to an international conference and later be published in a high-impact journal. In addition, we will disseminate the study results to the lung cancer patient community via a series of webinars; these webinars will be recorded and later shared with patient advocacy groups and lung cancer organizations.

Long-term Outcomes: Our data will yield insights to inform the oncology community of the barriers encountered by young patients with lung cancer and will allow us to develop the first clinical and research program for young patients with lung cancer in the nation.

Key words

Health equity

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Isotoxic hypofractionation to personalize radiation for NSCLC

2022

Veterans Affairs Research Scholar Award

Lucas Vitzthum, MD

Stanford University/VA Palo Alto

Palo Alto

The purpose of this study is to develop and evaluate a method for personalized radiation therapy in patients with locally advanced NSCLC. Patients will be assessed regarding their expected risk of treatment toxicity, and those at lower risk will be treated in a fewer number of treatments with a more intensified dose of radiation. If successful, this could be used to inform optimal radiation treatment protocols as well as potentially reduce treatment and financial burden for patients, with a major impact on quality of life.

Research Summary

Like all medical interventions, optimal management of lung cancer requires a careful assessment of risks and benefits with treatment. Patients presenting with larger lung tumors or those with cancer that has spread to the lymph nodes are often treated with definitive radiation therapy delivered daily over the course of several weeks. Depending on the location and size of tumors the risk of toxicity can vary greatly between patients. Despite these differences in presentation, patients are generally treated with a "one size fits all" approach to radiation dosing that is unlikely to adequately account for their risk from tumor progression versus treatment toxicity. The purpose of this proposal is to develop and test a method to personalize radiation therapy dosing based on a patient’s expected risk of treatment toxicity. Patients with a lower risk of toxicity will be treated in a fewer number of treatments which results in more time away from the clinic, lower costs, and a more ‘potent’ effective dose of radiation. We will enroll patients in a clinical trial to determine if this approach is safe and without significant toxicity. We will also evaluate how effective this regimen is at treating the cancer. The results of this study may be used to inform optimal radiation treatment for lung cancer or further guide subsequent larger randomized studies.

Technical Abstract

Despite recent advances, locally advanced non-small cell lung cancer (LA-NSCLC) continues to have a high degree of morbidity and mortality related to both disease progression and sequelae from treatment. The purpose of this study is to develop and evaluate a more personalized radiation therapy (RT) approach with the potential to reduce time and financial burden to patients and increase tumor control. Patients undergoing fractionated RT with concurrent systemic therapy for LA-NSCLC will be treated to a total dose of 60 Gy with the number of fractions determined by ability to meet key dose constraints resulting in a shorter treatment course and higher biologic effective dose (BED) among those treated with shorter fractionation. To reduce the iterative time to determine fractionation schedule and standardize the"‘isotoxic hypofractionation" approach, we will employ a previously developed automated RT planning technique after delineation of the tumor and organs at risk. Fifty patients will be enrolled in a prospective non-randomized 2-stage trial to test the primary objective of whether isotoxic hypofractionation results in an acceptable rate of grade 2 or higher toxicity. Secondary endpoints will include G3+ toxicity, local control, progression free survival and overall survival. Finally, to better inform future "isotoxic" dosing strategies we will evaluate additional predictors of radiation toxicity using established retrospective cohorts through the Stanford Cancer Institute and the Veteran’s Affairs Information and Computing Infrastructure (VINCI).

Key words

Metastatic

Radiotherapy

Stage III

Stage IV

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Addressing hepatic siphoning to enhance immunotherapy efficacy in veterans

2021

Veterans Affairs Research Scholar Award

Michael Green, MD

University of Michigan/Veterans Affairs Ann Arbor Healthcare System

Ann Arbor

Technical Abstract

Immune checkpoint inhibitors have revolutionized the care of patients with metastatic non-small cell lung cancer (NSCLC). Unfortunately, not all patients benefit from this therapy, and rational combinatorial strategies to enhance immune checkpoint inhibitors (ICI) efficacy in therapy non-responders are needed. We and others have shown that patients with liver metastases derive limited clinical benefit from ICI across a wide variety of disease types. In preclinical models, we discovered that liver metastases cause anti-PD-L1 resistance by siphoning tumor-specific T cells from systemic circulation. Within the liver, activated antigen-specific CD8+ T cells undergo apoptosis. Consequently, liver metastases create a systemic immune desert in preclinical models. Similarly, patients with liver metastases have reduced peripheral T cell numbers and diminished tumoral T cell diversity and function. In preclinical models, liver-directed radiotherapy eliminates immunosuppressive hepatic macrophages, increases hepatic T cell survival, and reduces hepatic siphoning of T cells. The central hypothesis of this proposal is that liver SBRT can enhance CPP therapy non-responders in NSCLC patients with liver metastases. In Aim 1, we will conduct a Phase IB clinical trial establishing the feasibility of delivering multi-target liver SBRT following the first cycle of carboplatin, pembrolizumab, and pemetrexed (CPP) in metastatic NSCLC patients with liver metastases. Up to four liver metastases will be targeted. In Aim 2, we will determine whether liver SBRT combined with ipilimumab and nivolumab modulates the hepatic and systemic immune microenvironment in NSCLC patients with liver metastases. The completion of these aims will assess the feasibility of ablating liver metastases with SBRT in combination with chemoimmunotherapy and deepen our understanding of the contribution of hepatic immune tolerance mechanisms in patients. The ultimate goal of this work is to test rationally-developed combinatorial treatment approaches in hopes of improving the care of NSCLC patients.

Key words

Immunotherapy

Metastatic

Stage III

Stage IV

Veterans Affairs

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Molecular Characterization of Lineage Plasticity

2021

Partner Awards

Grant title (if any)

EGFR Resisters/LUNGevity Lung Cancer Research Award

Helena Yu, MD

Memorial Sloan Kettering Cancer Center

New York

As a mechanism of resistance to EGFR inhibitors, cancers can change histology from adenocarcinoma to small cell or squamous cell lung cancer. Once this happens, EGFR inhibitors are no longer effective treatment; there are no strategies currently available to prevent or reverse transformation after it has occurred. Dr. Yu will use advanced molecular techniques to identify genetic changes that contribute to transformation. Understanding these genetic changes will identify biomarkers that can be utilized to develop treatments to prevent and reverse transformation.

Research Summary

Metastatic EGFR-mutant lung cancer remains an incurable disease despite significant advances in cancer therapeutics. With better EGFR inhibitors, we have identified new mechanisms of resistance that are independent of EGFR signaling, notably small cell and squamous cell histologic transformation. Targeted therapies are ineffective and survival is shortened once transformation has occurred, and no strategies are available to prevent or reverse transformation after it has occurred.

Mutations in EGFR, TP53, and RB1 are associated with transformation, but additional genetic or epigenetic changes must occur for transformation to happen. We will use advanced molecular techniques to identify the mutations and cell signaling pathways that drive transformation in order to identify biomarkers that can be utilized to develop treatments to prevent and reverse transformation. Treatments will then be validated in our unique pre-clinical models which can be rapidly translated into clinical trials, providing treatments for these aggressive cancers.

Technical Abstract

EGFR-mutant lung cancers (LC) serve as the prototype oncogene-driven cancer and mechanisms of resistance to EGFR therapy are well-established. Selective pressure of EGFR inhibitors can induce lineage plasticity to escape oncogene-dependence. While we have shown EGFR/TP53/RB1-mutations are necessary but insufficient to induce small cell transformation, no other genomic signatures and transcriptomic/epigenomic effectors that induce transformation have been identified.

Using parallel exome sequencing, bulk RNA sequencing, and bisulfite sequencing, we will characterize the biomarkers of transformation in EGFR/TP53/RB1-mutant LC and mixed adenocarcinoma/squamous cell tumors. We will also utilize single-cell RNA sequencing to identify the transcriptional changes associated with transformation and to identify distinct cell types within a heterogenous tumor. We will reconstruct a phenotypic landscape to identify subclones in a transitional state between histologies. The information obtained from these studies will nominate novel biomarkers of lineage plasticity that will be validated and proposed for study in clinical trials.

Key words

Acquired resistance

Biomarker or biomarker testing

Epidermal growth factor receptor (EGFR)

Metastatic

Molecular profile or molecular testing

Mutation profile

Tyrosine kinase inhibitors (TKIs)

Stage III

Stage IV

Targeted therapy

Tumor microenvironment

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SCLC molecular subtypes to predict targeted and immune therapy response

2020

Career Development Award

Carl Gay, MD, PhD

The University of Texas MD Anderson Cancer Center

Houston

Dr. Gay and his team will test an immunotherapy-DNA damage response (DDR) inhibitor combination therapy in SCLC patients and validate a biomarker profile. Dr. Gay’s research aims to develop a new drug therapy combination and determine which patients are likely to benefit from it.

Research Summary

Small cell lung cancer (SCLC) is among the most aggressive malignancies. While this disease responds initially to standard of care therapy, the tumors rapidly develop resistance to these and other available treatments, leading to limited patient survival. Unlike other cancers, where personalized medicine has markedly improved outcomes, small cell lung cancer patients are treated homogeneously, with little understanding of the patients that might best benefit from a specific therapy. Immunotherapy, which has so greatly impacted many other cancers, has shown modest, but promising efficacy for small cell lung cancer patients. We have demonstrated previously that in small cell lung cancer models, immunotherapy response may be enhanced using a class of drugs known as DNA damage repair (DDR) inhibitors. Furthermore, we have developed a potential strategy for optimally identifying patients for DDR inhibitors and immunotherapy using a molecular subtyping approach, which needs validation in patients. We propose using our unique collection of patient-derived mouse models of SCLC, as well as an upcoming trial pairing DDR inhibitors and immunotherapy, to validate our hypothesis. We predict that specific molecular subtypes predict innate sensitivity/resistance and that the ability of SCLC to switch subtypes may underlie acquired resistance. We will examine mouse models and patient samples representing each of the four molecular subtypes and validate predictions for best responses, while performing careful comparisons between samples collected pre- and post-treatment to explore mechanisms of resistance in an attempt to guide future clinical trials aimed at personalization of SCLC therapy.

Technical Abstract

Small cell lung cancer (SCLC) is an aggressive, neuroendocrine malignancy that accounts for approximately 15% of lung cancers. Despite recent advances, including the approval of immunotherapy combined with chemotherapy for frontline treatment, the median overall survival for patients with extensive-stage SCLC remains approximately one year. These dismal outcomes are attributable, in part, to the lack of approved biomarkers for SCLC, which, in turn, is due to the dearth of available tissue for molecular analysis. Using transcriptomic data, we have developed a gene signature that defines four distinct molecular subtypes of SCLC – each with unique biology and therapeutic vulnerabilities. These subtypes are driven by the presence (or absence) of three transcription factors (ASCL1 – SCLC-A; NEUROD1 – SCLC-N; POU2F3 – SCLC-P; and a fourth triple-negative subtype “Inflamed” – SCLC-I) that are largely mutually exclusive. Our preliminary data suggests that inter- and intra-tumoral heterogeneity among these subtypes drives response and resistance to standard and novel therapies for SCLC, including classes such as PARP inhibitors (PARPi) and immunotherapy. We propose applying bulk and single-cell molecular approaches to assign and longitudinally monitor subtype among our established cohort of patient-derived xenograft models treated with PARPi, as well as patient tumor biopsies from an investigator-initiated trial assessing a PARPi/immunotherapy combination. Based on our preliminary data, we hypothesize that SCLC-P and SCLC-I will preferentially benefit from PARP inhibitors and immunotherapy, respectively, and that subtype shifts detectable at the single-cell level along with accompanying shifts in the composition of the immune microenvironment, will govern response and resistance.

Key words

Acquired resistance

Biomarker or biomarker testing

Circulating tumor DNA

Immunotherapy

Tumor microenvironment

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Signaling Heterogeneity in Small Cell Lung Cancer

2016

Career Development Award

Jonathan Lehman, MD, PhD

Vanderbilt University Medical Center

Nashville

Chemotherapy has been the mainstay for treatment of small cell lung cancer (SCLC)—a highly aggressive subtype of lung cancer—for the past three decades. SCLC responds well to initial treatment but inevitably comes back. No targeted therapy is currently available for patients with SCLC. Dr. Lehman is studying how SCLC becomes resistant to chemotherapy. His research will further our understanding of chemotherapy resistance and identify novel targets for SCLC treatment.

Research Summary

Small cell lung cancer (SCLC) is the most aggressive and lethal type of lung cancer. Patients do well initially, but the cancer inevitably returns with resistance to further treatment. Patient survival is dismal, with most patients dying within a year of diagnosis. Treatment has not changed or improved significantly in the last 20 years. The most likely explanation for this rapid relapse after treatment is a resistant subpopulation of cancer cells that persist after chemotherapy. Research suggests that SCLC is a very heterogeneous cancer with multiple different cancer cells that communicate which each other. This proposal expands on preliminary data that has identified multiple novel subpopulations of cells. Dr. Lehman and his team aim to better identify this diversity in human small cell by using a novel technique that can identify levels of more than 40 different cell surface markers simultaneously in individual cells. This gives them a signaling and surface marker “map.” They will then compare this map with maps from human tumors grown in mice before and after chemotherapy treatment to find out how these tumors change with treatment. Finally, they will test new treatments based on killing or disrupting specific subpopulations of cells in order to interfere with cancer growth, potentially leading to new, more specific or targeted treatment strategies for SCLC.

Technical Abstract

Small cell lung cancer (SCLC) is among the most aggressive and deadly human cancers. It represents approximately 15% of all lung cancers, and it is responsible for over 30,000 deaths in the US and 200,000 deaths worldwide every year. SCLC responds to treatment but recurs frequently and aggressively, with the majority of patients dying within 12 months of diagnosis. No targeted therapies are yet available for SCLC. New strategies are needed to improve outcomes for patients with SCLC. This project will expand upon preliminary data identifying at least two distinct subpopulations of cells in SCLC cell lines and patient-derived xenografts comprising a neuroendocrine (NE) and mesenchymal-like (ML) set of cell line populations. Dr. Lehman and his team will use an innovative approach using mass cytometry, using rare earth antibody conjugates to antibody label more than 30 proteins simultaneously, including phospho and signaling proteins. This technique will establish at a single-cell resolution tumor heterogeneity and signaling in small cell lung carcinoma in multiple primary human samples as well as in patient-derived xenograft samples before and after chemotherapy treatment. This proposal aims to (1) characterize the signaling of subpopulations in human primary SCLCs at a single-cell resolution, (2) identify changes in tumor heterogeneity and in these subpopulations after chemotherapy treatment and relapse, and (3) disrupt and manipulate developmental signaling/ associated subpopulations (prototypically the HH [Hedgehog] and Notch/DLL3 pathways) to reduce tumor burden and lead to targeted rational combination therapy for SCLC.

Key words

Acquired resistance

Targeted therapy

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Lung screening via biophotonic analysis of nanoarchitecture of buccal cells

2015

Early Detection Research Award

This grant was funded in part by Upstage Lung Cancer

Vadim Backman, PhD

Northwestern University

Evanston

Ankit Bharat, MBBS

Northwestern University

Evanston

Cells in the respiratory tract are usually stacked in an orderly fashion. As lung cancer develops, the cells get “un-stacked” and their shapes change, giving them the ability to grow and spread to other parts of the body. Dr. Vadim Backman from Northwestern University is utilizing a new technology called Partial Wave Spectroscopy for seeing those cells. With the LUNGevity Early Detection Award, he will check how cells taken from the cheeks of stage I lung cancer patients reflect these early changes with the ultimate goal of using partial wave spectroscopy technology for early detection of lung cancer.

Research Summary

The goal of this project is to translate a state-of-the-art nanoscale imaging technology, nanocytology, into an inexpensive and accurate lung cancer screening method among current/past smokers via an automated analysis of nanoscale morphology of buccal (cheek) cells obtained by a simple check swab. Dr. Backman and his group envision buccal nanocytology becoming a prescreen for lung cancer that is simple and reliable enough to be performed by a primary care physician or dentist as part of an annual exam of current or past smokers. If the buccal PWS is positive, a patient can be offered more expensive/invasive diagnostic tests such as low dose CT.

This is analogous to the other two-tier screening approach: Pap smear --> colposcopy paradigm, where the initial low-cost, patient-compliant screening test is applied on the entire screening population and used to identify a small subset of these patients who would actually benefit from more extensive examination. This two-tier screening strategy has been highly successful in reducing cervical cancer mortality by 90%. Their goal is to develop a similar approach for lung cancer screening.

Technical Abstract

The overarching goal of the project is to develop a new technology for accurate and cost-effective lung cancer screening in current/former smokers. Lung cancer is curable if detected early. However, there are no robust screening techniques with options such as CT scans fraught with cost, harms, and a high false positive rate. Dr. Backman and his group hope to transform the clinical practice of lung cancer screening by exploiting field carcinogenesis, the concept that the genetic/environmental milieu that results in lung tumor impacts upon the entire aerodigestive mucosa including the buccal mucosa, which was referred to as a “molecular mirror” of lung carcinogenesis.

Their data show that the alteration of nanoscale architecture of buccal cells is exquisitely sensitive to lung field carcinogenesis and may serve as a robust biomarker for lung cancer. These nanoarchitectural changes can be detected in a practical and highly accurate fashion via a new technology, partial wave spectroscopic (PWS) microscopy (‘nanocytology’).

In the proposed study, they will conduct a blinded validation case-control trial to determine the sensitivity and specificity of buccal nanocytology for lung cancer. They will evaluate the ability of the test to identify patients who have lung cancer and how many patients with lung cancer would be missed using this technique. They will perform a subgroup analysis for Stage I lung cancers. They will assess the potential confounding effects of smoking frequency and time of cessation and other aerodigestive malignancies.

This project will provide the requisite data for the future definitive multicenter validation trial followed by FDA submission.

Key words

Early detection

Screening

Stage - all

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Enhancement of the Efficacy of Chemotherapy for Lung Cancer by Simultaneous Suppression of Multi-drug Resistance and Antiapoptotic Cellular Defenses

2003

Targeted Therapeutics Research Award

Funded equally by LUNGevity Foundation and American Lung Association National Office

Tamara Minko, PhD

Rutgers University

Highland Park

Cancer cells develop resistance to chemotherapy drugs by 1) making proteins that neutralize the effects of chemotherapy (through a protein called Bcl-2) and 2) developing pumping systems that expel the drugs out of the cells (through a protein called MRP). Dr. Minko is studying how stopping the Bcl2 and MRP proteins will make lung cancer cells more sensitive to chemotherapy drugs.

Key words

Chemotherapy