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Force, Jeremy M

Positions:

Medical Instructor in the Department of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

D.O. 2011

D.O. — University of New England

Internal Medicine Residency

Indiana University School of Medicine

Hematology/Oncology Fellowship, Medicine

Duke University School of Medicine

Grants:

Regional Oncolytic Poliovirus Immunotherapy for Breast Cancer

Administered By
Surgery, Surgical Sciences
AwardedBy
Department of Defense
Role
Collaborator
Start Date
August 01, 2016
End Date
July 31, 2021

Publications:

First-line treatment of metastatic melanoma: role of nivolumab.

Historically, the median overall survival of metastatic melanoma patients was less than 1 year and long-term survivors were rare. Recent advances in therapies have dramatically shifted this landscape with increased survival rates and the real possibility that long-term disease control is achievable. Advances in immune modulators, including cytotoxic T-lymphocyte antigen-4 and programmed death-1 based treatments, have been an integral part of this success. In this article, we review previous and recent therapeutic developments for metastatic melanoma patients. We discuss advances in immunotherapy while focusing on the use of nivolumab alone and in combination with other agents, including ipilimumab in advanced melanoma. One major goal in melanoma research is to optimize combination strategies allowing for more patients to experience benefit while minimizing toxicity. A better understanding of the optimal sequencing, combinations, and mechanisms underlying the development of resistance may provide evidence for rational clinical trial designs of novel immunotherapy strategies in melanoma and other cancer subtypes.

Authors
Force, J; Salama, AK
MLA Citation
Force, J, and Salama, AK. "First-line treatment of metastatic melanoma: role of nivolumab." ImmunoTargets and therapy 6 (January 2017): 1-10. (Review)
Website
http://hdl.handle.net/10161/15631
PMID
28243579
Source
epmc
Published In
ImmunoTargets and Therapy
Volume
6
Publish Date
2017
Start Page
1
End Page
10
DOI
10.2147/itt.s110479

Nodular Regenerative Hyperplasia After Treatment With Trastuzumab Emtansine.

Authors
Force, J; Saxena, R; Schneider, BP; Storniolo, AM; Sledge, GW; Chalasani, N; Vuppalanchi, R
MLA Citation
Force, J, Saxena, R, Schneider, BP, Storniolo, AM, Sledge, GW, Chalasani, N, and Vuppalanchi, R. "Nodular Regenerative Hyperplasia After Treatment With Trastuzumab Emtansine." Journal of clinical oncology : official journal of the American Society of Clinical Oncology 34.3 (January 2016): e9-12.
PMID
24778392
Source
epmc
Published In
Journal of Clinical Oncology
Volume
34
Issue
3
Publish Date
2016
Start Page
e9
End Page
12
DOI
10.1200/jco.2013.49.8543

Assessment of objective responses using volumetric evaluation in advanced thymic malignancies and metastatic non-small cell lung cancer.

Measurement of tumor response by standard response criteria is challenging in thymic malignancies, especially when the pleura is involved, as it often is in stage IV disease. In this study, we aimed to determine the effectiveness of volumetric response evaluation criteria in solid tumors (volumetrics) for evaluating response in patients with thymic malignancies treated on a phase II study of belinostat.We evaluated the tumor responses of 25 patients with thymic cancer using computed tomography-based RECIST, World Health Organization (WHO), modified RECIST, and volumetrics. As a control, we assessed 37 patients with non-small cell lung cancer (NSCLC) with RECIST and volumetrics.Agreement analyses in 23 patients with thymic cancer at the time of RECIST-determined progressive disease (PD) compared volumetrics with RECIST, modified RECIST, and WHO criteria. Use of volumetrics was associated with 22% discordance compared with RECIST, 15% versus modified RECIST, and 22% versus WHO criteria. Volumetrics revealed PD 72 days earlier than RECIST (p = 0.016). In another cohort of 35 patients with NSCLC, there was 9% discordance between volumetrics and RECIST at the time of PD. Volumetrics demonstrated PD 32 days earlier than RECIST in NSCLC (p = 0.0078).Our study suggests that volumetrics might improve detection of PD. Prospective evaluation of this technique in a larger series of patients with thymic malignancies will be required.

Authors
Force, J; Rajan, A; Dombi, E; Steinberg, SM; Giaccone, G
MLA Citation
Force, J, Rajan, A, Dombi, E, Steinberg, SM, and Giaccone, G. "Assessment of objective responses using volumetric evaluation in advanced thymic malignancies and metastatic non-small cell lung cancer." Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 6.7 (July 2011): 1267-1273.
PMID
21610525
Source
epmc
Published In
Journal of Thoracic Oncology
Volume
6
Issue
7
Publish Date
2011
Start Page
1267
End Page
1273
DOI
10.1097/jto.0b013e3182199be2

Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib.

Sorafenib, a multikinase inhibitor targeting Raf and VEGFR, has shown activity in unselected patients with non-small-cell lung cancer (NSCLC). At present there are no validated biomarkers indicative of sorafenib activity.Patients received sorafenib 400 mg BID daily to determine activity and tolerability and to measure its biological effects. KRAS mutation status (N = 34), angiogenesis markers (VEGF, bFGF, FLT-1, PLGF-1) and imaging with DCE-MRI (dynamic contrast enhanced MRI) to determine early changes in tumor vascular characteristics were evaluated. Three parameters K(trans), K(ep), and V(e) were measured by DCE-MRI at baseline and day 14 of cycle 1. Cytokine analysis was done on days 0, 14, 28, and 54.Thirty-seven patients with previously treated stage IV NSCLC were enrolled in this single-center phase II trial. In 34 evaluable patients, 2 had partial responses and 20 had stable disease for 3 to 17 months, a disease control rate of 65%. The median progression-free survival (PFS) was 3.4 months, and median overall survival (OS) was 11.6 months. Toxicity was consistent with the known side effects of sorafenib. KRAS (32%) and EGFR mutations (22%) showed no correlation with response, PFS, or OS. K(ep), was significant in predicting an improvement in OS (P = 0.035) and PFS (P = 0.029). Cytokine analysis demonstrated an improved OS for bFGF day 0 (<6 vs. >6 pg/mL; P = 0.042), whereas a PFS benefit was seen with bFGF at day 28 (<6 vs. >6; P = 0.028).KRAS and EGFR mutational status showed no correlation with response, PFS, or OS. Radiologic and cytokine changes may act as biomarkers indicative of early angiogenesis inhibition.

Authors
Kelly, RJ; Rajan, A; Force, J; Lopez-Chavez, A; Keen, C; Cao, L; Yu, Y; Choyke, P; Turkbey, B; Raffeld, M; Xi, L; Steinberg, SM; Wright, JJ; Kummar, S; Gutierrez, M; Giaccone, G
MLA Citation
Kelly, RJ, Rajan, A, Force, J, Lopez-Chavez, A, Keen, C, Cao, L, Yu, Y, Choyke, P, Turkbey, B, Raffeld, M, Xi, L, Steinberg, SM, Wright, JJ, Kummar, S, Gutierrez, M, and Giaccone, G. "Evaluation of KRAS mutations, angiogenic biomarkers, and DCE-MRI in patients with advanced non-small-cell lung cancer receiving sorafenib." Clinical cancer research : an official journal of the American Association for Cancer Research 17.5 (March 2011): 1190-1199.
PMID
21224376
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
17
Issue
5
Publish Date
2011
Start Page
1190
End Page
1199
DOI
10.1158/1078-0432.ccr-10-2331

Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin.

Current therapy for lung cancer involves multimodality therapies. However, many patients are either refractory to therapy or develop drug resistance. KRAS and epidermal growth factor receptor (EGFR) mutations represent some of the most common mutations in lung cancer, and many studies have shown the importance of these mutations in both carcinogenesis and chemoresistance. Genetically engineered murine models of mutant EGFR and KRAS have been developed that more accurately recapitulate human lung cancer. Recently, using cell-based experiments, we showed that platinum-based drugs and the antidiabetic drug rosiglitazone (PPARgamma ligand) interact synergistically to reduce cancer cell and tumor growth. Here, we directly determined the efficacy of the PPARgamma/carboplatin combination in these more relevant models of drug resistant non-small cell lung cancer.Tumorigenesis was induced by activation of either mutant KRAS or EGFR. Mice then received either rosiglitazone or carboplatin monotherapy, or a combination of both drugs. Change in tumor burden, pathology, and evidence of apoptosis and cell growth were assessed.Tumor burden remained unchanged or increased in the mice after monotherapy with either rosiglitazone or carboplatin. In striking contrast, we observed significant tumor shrinkage in mice treated with these drugs in combination. Immunohistochemical analyses showed that this synergy was mediated via both increased apoptosis and decreased proliferation. Importantly, this synergy between carboplatin and rosiglitazone did not increase systemic toxicity.These data show that the PPARgamma ligand/carboplatin combination is a new therapy worthy of clinical investigation in lung cancers, including those cancers that show primary resistance to platinum therapy or acquired resistance to targeted therapy.

Authors
Girnun, GD; Chen, L; Silvaggi, J; Drapkin, R; Chirieac, LR; Padera, RF; Upadhyay, R; Vafai, SB; Weissleder, R; Mahmood, U; Naseri, E; Buckley, S; Li, D; Force, J; McNamara, K; Demetri, G; Spiegelman, BM; Wong, K-K
MLA Citation
Girnun, GD, Chen, L, Silvaggi, J, Drapkin, R, Chirieac, LR, Padera, RF, Upadhyay, R, Vafai, SB, Weissleder, R, Mahmood, U, Naseri, E, Buckley, S, Li, D, Force, J, McNamara, K, Demetri, G, Spiegelman, BM, and Wong, K-K. "Regression of drug-resistant lung cancer by the combination of rosiglitazone and carboplatin." Clinical cancer research : an official journal of the American Association for Cancer Research 14.20 (October 2008): 6478-6486.
PMID
18927287
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
14
Issue
20
Publish Date
2008
Start Page
6478
End Page
6486
DOI
10.1158/1078-0432.ccr-08-1128

Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor.

There is an unmet need for noninvasive markers to measure the biological effects of targeted agents, particularly those inhibiting the vascular endothelial growth factor (VEGF) receptor (VEGFR) pathway, and identify patients most likely to benefit from treatment. In this study, we investigated potential blood-based biomarkers for SU11248 (sunitinib malate), a multitargeted tyrosine kinase inhibitor, in patients with metastatic imatinib-refractory gastrointestinal stromal tumors.Patients (n=73) enrolled in a phase I/II trial received SU11248 daily for 14 or 28 days followed by 14 days without treatment per cycle. Clinical benefit was defined as progression-free survival of >6 months. We assessed plasma markers, including VEGF and soluble VEGFR-2 (sVEGFR-2), and two cellular populations bearing VEGF receptors: monocytes and, in a subset of patients, mature circulating endothelial cells (CEC).Compared to patients with progressive disease, patients with clinical benefit had significantly greater increases in CECs (0.52 versus -0.01 CEC/microL/d, P=0.03) and smaller decreases in monocyte levels (47% versus 60%, P=0.007) during cycle 1. VEGF increased by 2.2-fold and sVEGFR-2 decreased 25% during the first 2 weeks of treatment. Neither plasma marker correlated with clinical outcome although a modest inverse correlation was observed between sVEGFR-2 changes and plasma drug levels. Monocytes, VEGF, and sVEGFR-2 all rebounded towards baseline off treatment.Monocytes, VEGF, and sVEGFR-2 were consistently modulated by treatment, suggesting that they may serve as pharmacodynamic markers for SU11248. Changes in CECs and monocytes, but not the plasma markers, differed between the patients with clinical benefit and those with progressive disease. These end points merit further investigation in future trials to determine their utility as markers of SU11248 activity and clinical benefit in gastrointestinal stromal tumors and other tumor types.

Authors
Norden-Zfoni, A; Desai, J; Manola, J; Beaudry, P; Force, J; Maki, R; Folkman, J; Bello, C; Baum, C; DePrimo, SE; Shalinsky, DR; Demetri, GD; Heymach, JV
MLA Citation
Norden-Zfoni, A, Desai, J, Manola, J, Beaudry, P, Force, J, Maki, R, Folkman, J, Bello, C, Baum, C, DePrimo, SE, Shalinsky, DR, Demetri, GD, and Heymach, JV. "Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor." Clinical cancer research : an official journal of the American Association for Cancer Research 13.9 (May 2007): 2643-2650.
PMID
17473195
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
13
Issue
9
Publish Date
2007
Start Page
2643
End Page
2650
DOI
10.1158/1078-0432.ccr-06-0919

Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve.

We show here that recombinant endostatin protein has a biphasic effect on the inhibition of endothelial cell migration in vitro. In tumor-bearing animals, there is a similar biphasic effect on the inhibition of tumor growth and on circulating endothelial cells after once-daily s.c. injections. This biphasic effect is revealed as a U-shaped curve in which efficacy is optimal between very low and very high doses depending on the tumor type. This result may be applicable to other inhibitors of endothelial growth and to angiogenesis. Furthermore, these results have important implications for clinicians who administer angiogenesis inhibitors for cancer or other angiogenesis-dependent diseases. When these results are taken together with two previous reports of angiogenesis inhibitors with a U-shaped dose-response, they suggest that other regulators of endothelial growth may display a similar pattern.

Authors
Celik, I; Sürücü, O; Dietz, C; Heymach, JV; Force, J; Höschele, I; Becker, CM; Folkman, J; Kisker, O
MLA Citation
Celik, I, Sürücü, O, Dietz, C, Heymach, JV, Force, J, Höschele, I, Becker, CM, Folkman, J, and Kisker, O. "Therapeutic efficacy of endostatin exhibits a biphasic dose-response curve." Cancer research 65.23 (December 2005): 11044-11050.
PMID
16322254
Source
epmc
Published In
Cancer Research
Volume
65
Issue
23
Publish Date
2005
Start Page
11044
End Page
11050
DOI
10.1158/0008-5472.can-05-2617

Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity.

Circulating endothelial cells (CEC) comprise at least two distinct populations: bone marrow-derived circulating endothelial progenitors (CEP) and mature CECs derived from existing vasculature. We hypothesized that antiangiogenic agents may have differential effects on CEPs and mature CECs and that these changes may serve as a marker of biological activity.The effect of angiogenesis inhibitors on CECs was evaluated by flow cytometry after vascular endothelial growth factor (VEGF)-induced mobilization and in mice bearing Lewis lung carcinoma (LLC). Tumor angiogenesis was evaluated in parallel by immunohistochemistry.In nontumor-bearing mice, VEGF administration increased both mature CECs and CEPs. This increase was inhibited by the VEGF receptor 2 inhibitor ZD6474 as well as the VEGF inhibitor-soluble Flt-1. ZD6474 had no significant effect on CECs in the absence of exogenous VEGF stimulation. In contrast, LLC-bearing mice had an increase in mature CECs but not CEPs after 3 days of treatment with ZD6474. The increase in mature CECs was dose-dependent, accompanied by a decrease in tumor microvessel density, and preceded reduction in tumor volume. Treatment of LLC-bearing mice with the vascular targeting agent ZD6126 also increased mature CECs.VEGF inhibitors can have differential effects on mature CECs and CEPs, and agents inhibiting tumor angiogenesis may cause a concomitant increase in mature CECs. This increase occurs in tumor-bearing but not in nontumor-bearing mice, suggesting that tumor endothelium is a potential source of mature CECs. Therefore, assessing both mature CECs and CEPs may provide insights into the mechanism of antiangiogenic agents and serve as an early surrogate marker of biological activity.

Authors
Beaudry, P; Force, J; Naumov, GN; Wang, A; Baker, CH; Ryan, A; Soker, S; Johnson, BE; Folkman, J; Heymach, JV
MLA Citation
Beaudry, P, Force, J, Naumov, GN, Wang, A, Baker, CH, Ryan, A, Soker, S, Johnson, BE, Folkman, J, and Heymach, JV. "Differential effects of vascular endothelial growth factor receptor-2 inhibitor ZD6474 on circulating endothelial progenitors and mature circulating endothelial cells: implications for use as a surrogate marker of antiangiogenic activity." Clinical cancer research : an official journal of the American Association for Cancer Research 11.9 (May 2005): 3514-3522.
PMID
15867254
Source
epmc
Published In
Clinical cancer research : an official journal of the American Association for Cancer Research
Volume
11
Issue
9
Publish Date
2005
Start Page
3514
End Page
3522
DOI
10.1158/1078-0432.ccr-04-2271

Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells.

Circulating endothelial cells (CECs) are present in peripheral blood and have been shown to contribute to normal and pathological neovascularization. Antiangiogenic molecules can inhibit neovascularization in tumors and other sites, but their effect on CECs has not yet been determined. We hypothesize that angiogenic factors will increase the number of CECs, and conversely, antiangiogenic treatment will reduce these numbers. Mice treated with high levels of vascular endothelial growth factor (VEGF) showed increased numbers of Flk-1-positive cells in peripheral blood and endothelial cell colonies compared with vehicle-treated controls. These changes were accompanied by increased bone marrow neovascularization. In contrast, mice that received VEGF and endostatin had significantly lower numbers of CECs and reduced bone marrow vascularization. Endostatin-induced apoptosis was probably responsible for the decreased number of CECs. Systemic delivery of a VEGF antagonist, soluble Flt-1, also inhibited the VEGF-induced increase in CECs. These results were further confirmed in a Tie2/LacZ mouse model, in which endostatin reduced the number of beta-galactosidase-expressing peripheral blood mononuclear cells. We propose that endothelial progenitor cells are a novel target for endostatin and suggest that the relative numbers of CECs can serve as a surrogate marker for the biological activity of antiangiogenic treatment.

Authors
Schuch, G; Heymach, JV; Nomi, M; Machluf, M; Force, J; Atala, A; Eder, JP; Folkman, J; Soker, S
MLA Citation
Schuch, G, Heymach, JV, Nomi, M, Machluf, M, Force, J, Atala, A, Eder, JP, Folkman, J, and Soker, S. "Endostatin inhibits the vascular endothelial growth factor-induced mobilization of endothelial progenitor cells." Cancer research 63.23 (December 2003): 8345-8350.
PMID
14678995
Source
epmc
Published In
Cancer Research
Volume
63
Issue
23
Publish Date
2003
Start Page
8345
End Page
8350
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Research Areas:

  • APOBEC
  • Apobec
  • BRCA genes
  • Breast--Cancer--Immunotherapy
  • Cancer/testis Antigens
  • Homologous Recombination
  • Inflammatory Breast Cancer
  • Nanostring
  • Tumor Immune Microenvironment
  • Tumor Infiltrating Lymphocytes
  • X Chromosome Inactivation
  • X chromosome--Abnormalities