2022 Southern Medical Research Conference




tonsil cancer metastasis to lung :: Article Creator

Surviving Stage 4 Lung Cancer: A Personal Story

Since then, Ed has worked closely with his care team at the Tampa Moffitt Cancer Center and together they came up with a treatment plan. His healthcare providers decided that Ed would benefit from a three-drug chemotherapy approach. This was because he didn't have an actionable biomarker and targeted therapies weren't an option.

Unfortunately, over time the chemotherapy became less effective, so Ed and his oncologist decided to try a Phase One immunotherapy trial. "Both my wife and I were scared. We had young grandchildren and so many things that we wanted to see and do with them. And I was afraid I was going to miss all of that, when chemo stopped working for me." The first clinical trial caused Ed to experience extreme side effects, so he and his oncologist decided to switch to a different Phase One immunotherapy trail, which quickly began to work. Within a year, Ed's condition stabilized and has remained so for five years after he started.

Ed shared that "There is hope. We are living long lives now, long fruitful lives where we can enjoy being with our family." He recommends getting a biomarker test, so that proper treatment can be determined and that a second opinion can be helpful.

"At my first oncologist appointment, I was told I had only 9-12 months left to live without treatment. But I wasn't ready to give up. I wanted to explore all my options," Ed said. This was nearly 10 years ago. Looking forward, in April 2022, Ed was declared to have "no evidence of disease" and remains so to this day. After surviving stage 4 Lung Cancer, Ed is determined to help others, so he has become an advocate, leading efforts to improve the lives of people diagnosed with lung cancer.

Visit Lung.Org/Liver-Mets for more information.

Support made possible by Regeneron and Sanofi Genzyme.


Metastasis: From Dissemination To Organ-specific Colonization

  • Christofori, G. New signals from the invasive front. Nature 441, 444–450 (2006).

    CAS  PubMed  Google Scholar 

  • Gupta, G. P. & Massague, J. Cancer metastasis: building a framework. Cell 127, 679–695 (2006).

    CAS  PubMed  Google Scholar 

  • Steeg, P. S. Tumor metastasis: mechanistic insights and clinical challenges. Nature Med. 12, 895–904 (2006).

    CAS  PubMed  Google Scholar 

  • Fidler, I. J. The pathogenesis of cancer metastasis: the 'seed and soil' hypothesis revisited. Nature Rev. Cancer 3, 453–458 (2003).

    CAS  Google Scholar 

  • Paget, S. The distribution of secondary growths in cancer of the breast. 1889. Cancer Metastasis Rev. 8, 98–101 (1989).

    CAS  PubMed  Google Scholar 

  • Yin, J. J. Et al. TGF-β signaling blockade inhibits PTHrP secretion by breast cancer cells and bone metastases development. J. Clin. Invest. 103, 197–206 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Minn, A. J. Et al. Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors. J. Clin. Invest. 115, 44–55 (2005). This paper shows that pleural effusion-derived metastatic cell populations are heterogeneous in their ability to colonize different organs, supporting the notion that various target organs impose different requirements on arriving tumour cells.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Minn, A. J. Et al. Genes that mediate breast cancer metastasis to lung. Nature 436, 518–524 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kang, Y. Et al. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3, 537–549 (2003). This paper shows that in vivo selection enriches for bone metastatic ability and identifies genetic mediators of bone metastatic colonization.

    CAS  PubMed  Google Scholar 

  • Edlund, M., Sung, S. Y. & Chung, L. W. Modulation of prostate cancer growth in bone microenvironments. J. Cell. Biochem. 91, 686–705 (2004).

    CAS  PubMed  Google Scholar 

  • Triozzi, P. L., Eng, C. & Singh, A. D. Targeted therapy for uveal melanoma. Cancer Treat. Rev. 34, 247–258 (2008).

    CAS  PubMed  Google Scholar 

  • Hess, K. R. Et al. Metastatic patterns in adenocarcinoma. Cancer 106, 1624–1633 (2006). A recent clinical study that reports the frequency of organ-specific relapse in 11 different types of adenocarcinomas from over 4,000 patients.

    PubMed  Google Scholar 

  • Patanaphan, V., Salazar, O. M. & Risco, R. Breast cancer: metastatic patterns and their prognosis. South. Med. J. 81, 1109–1112 (1988).

    CAS  PubMed  Google Scholar 

  • Schmidt-Kittler, O. Et al. From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc. Natl Acad. Sci. USA 100, 7737–7742 (2003). This paper shows that disseminated tumour cells have different and fewer aberrations than their matched primary tumours, suggesting that dissemination is an early event during cancer development.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Karrison, T. G., Ferguson, D. J. & Meier, P. Dormancy of mammary carcinoma after mastectomy. J. Natl Cancer Inst. 91, 80–85 (1999).

    CAS  PubMed  Google Scholar 

  • Feld, R., Rubinstein, L. V. & Weisenberger, T. H. Sites of recurrence in resected stage I non-small-cell lung cancer: a guide for future studies. J. Clin. Oncol. 2, 1352–1358 (1984).

    CAS  PubMed  Google Scholar 

  • Hoffman, P. C., Mauer, A. M. & Vokes, E. E. Lung cancer. Lancet 355, 479–485 (2000).

    CAS  PubMed  Google Scholar 

  • Chambers, A. F., Groom, A. C. & MacDonald, I. C. Dissemination and growth of cancer cells in metastatic sites. Nature Rev. Cancer 2, 563–572 (2002).

    CAS  Google Scholar 

  • Hanahan, D. & Weinberg, R. A. The hallmarks of cancer. Cell 100, 57–70 (2000).

    CAS  PubMed  Google Scholar 

  • Moody, S. E. Et al. Conditional activation of Neu in the mammary epithelium of transgenic mice results in reversible pulmonary metastasis. Cancer Cell 2, 451–461 (2002).

    CAS  PubMed  Google Scholar 

  • Slamon, D. J. Et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344, 783–792 (2001).

    CAS  PubMed  Google Scholar 

  • Minna, J. D., Kurie, J. M. & Jacks, T. A big step in the study of small cell lung cancer. Cancer Cell 4, 163–166 (2003).

    CAS  PubMed  Google Scholar 

  • Klein, C. A. The systemic progression of human cancer: a focus on the individual disseminated cancer cell—the unit of selection. Adv. Cancer Res. 89, 35–67 (2003).

    CAS  PubMed  Google Scholar 

  • Chiang, A. C. & Massagué, J. Molecular basis of metastasis. N. Engl. J. Med. 359, 2814–2823 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nguyen, D. X. & Massagué, J. Genetic determinants of cancer metastasis. Nature Rev. Genet. 8, 341–352 (2007).

    CAS  PubMed  Google Scholar 

  • Yang, J. & Weinberg, R. A. Epithelial–mesenchymal transition: at the crossroads of development and tumor metastasis. Dev. Cell 14, 818–829 (2008).

    CAS  PubMed  Google Scholar 

  • Hu, G. Et al. MTDH activation by 8q22 genomic gain promotes chemoresistance and metastasis of poor-prognosis breast cancer. Cancer Cell 15, 9–20 (2009). A study that mechanistically links the pro-metastatic gene metadherin with resistance to chemotherapy.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Stein, U. Et al. MACC1, a newly identified key regulator of HGF–MET signaling, predicts colon cancer metastasis. Nature Med. 15, 59–67 (2009).

    CAS  PubMed  Google Scholar 

  • Guo, C. Et al. The noncoding RNA, miR-126, suppresses the growth of neoplastic cells by targeting phosphatidylinositol 3-kinase signaling and is frequently lost in colon cancers. Genes Chromosomes Cancer 47, 939–946 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tavazoie, S. F. Et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature 451, 147–152 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Mundy, G. R. Metastasis to bone: causes, consequences and therapeutic opportunities. Nature Rev. Cancer 2, 584–593 (2002).

    CAS  Google Scholar 

  • Lee, Y. T. Patterns of metastasis and natural courses of breast carcinoma. Cancer Metastasis Rev. 4, 153–172 (1985).

    CAS  PubMed  Google Scholar 

  • Johansson, J. E. Et al. Natural history of early, localized prostate cancer. JAMA 291, 2713–2719 (2004).

    CAS  PubMed  Google Scholar 

  • Nieto, J., Grossbard, M. L. & Kozuch, P. Metastatic pancreatic cancer 2008: is the glass less empty? Oncologist 13, 562–576 (2008).

    CAS  PubMed  Google Scholar 

  • Fearon, E. R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759–767 (1990).

    CAS  PubMed  Google Scholar 

  • Kinzler, K. W. & Vogelstein, B. Lessons from hereditary colorectal cancer. Cell 87, 159–170 (1996).

    CAS  PubMed  Google Scholar 

  • Vogelstein, B. Et al. Genetic alterations during colorectal-tumor development. N. Engl. J. Med. 319, 525–532 (1988).

    CAS  PubMed  Google Scholar 

  • Samuels, Y. Et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 304, 554 (2004).

    CAS  PubMed  Google Scholar 

  • Baker, S. J. Et al. Chromosome 17 deletions and p53 gene mutations in colorectal carcinomas. Science 244, 217–221 (1989).

    CAS  PubMed  Google Scholar 

  • Markowitz, S. Et al. Inactivation of the type II TGF-β receptor in colon cancer cells with microsatellite instability. Science 268, 1336–1338 (1995).

    CAS  PubMed  Google Scholar 

  • Jones, S. Et al. Comparative lesion sequencing provides insights into tumor evolution. Proc. Natl Acad. Sci. USA 105, 4283–4288 (2008). A study that evaluated the frequency and timing of somatic mutations to estimate the clinical course of colorectal metastatic progression.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kedrin, D., van Rheenen, J., Hernandez, L., Condeelis, J. & Segall, J. E. Cell motility and cytoskeletal regulation in invasion and metastasis. J. Mammary Gland Biol. Neoplasia 12, 143–152 (2007).

    PubMed  Google Scholar 

  • Weber, G. F. Molecular mechanisms of metastasis. Cancer Lett. 270, 181–190 (2008).

    CAS  PubMed  Google Scholar 

  • Clark, E. A., Golub, T. R., Lander, E. S. & Hynes, R. O. Genomic analysis of metastasis reveals an essential role for RhoC. Nature 406, 532–535 (2000).

    CAS  PubMed  Google Scholar 

  • Ewald, A. J., Brenot, A., Duong, M., Chan, B. S. & Werb, Z. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Dev. Cell 14, 570–581 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kouros-Mehr, H. Et al. GATA-3 links tumor differentiation and dissemination in a luminal breast cancer model. Cancer Cell 13, 141–152 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Podsypanina, K. Et al. Seeding and propagation of untransformed mouse mammary cells in the lung. Science 321, 1841–1844 (2008). This paper showed that phenotypically normal mouse mammary cells introduced into the mouse circulation can infiltrate the lungs and survive, leading to tumour initiation.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ince, T. A. Et al. Transformation of different human breast epithelial cell types leads to distinct tumor phenotypes. Cancer Cell 12, 160–170 (2007). This study showed that there are intrinsic differences in the tumorigenic and metastatic capabilities of different mammary cell types.

    CAS  PubMed  Google Scholar 

  • Mani, S. A. Et al. The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 133, 704–715 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Bandyopadhyay, S. Et al. Interaction of KAI1 on tumor cells with DARC on vascular endothelium leads to metastasis suppression. Nature Med. 12, 933–938 (2006).

    CAS  PubMed  Google Scholar 

  • Karpatkin, S. & Pearlstein, E. Role of platelets in tumor cell metastases. Ann. Intern. Med. 95, 636–641 (1981).

    CAS  PubMed  Google Scholar 

  • Nieswandt, B., Hafner, M., Echtenacher, B. & Mannel, D. N. Lysis of tumor cells by natural killer cells in mice is impeded by platelets. Cancer Res. 59, 1295–1300 (1999).

    CAS  PubMed  Google Scholar 

  • Im, J. H. Et al. Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res. 64, 8613–8619 (2004).

    CAS  PubMed  Google Scholar 

  • Jain, S. Et al. Platelet glycoprotein Ibα supports experimental lung metastasis. Proc. Natl Acad. Sci. USA 104, 9024–9028 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Paku, S., Dome, B., Toth, R. & Timar, J. Organ-specificity of the extravasation process: an ultrastructural study. Clin. Exp. Metastasis 18, 481–492 (2000).

    CAS  PubMed  Google Scholar 

  • Lalor, P. F., Lai, W. K., Curbishley, S. M., Shetty, S. & Adams, D. H. Human hepatic sinusoidal endothelial cells can be distinguished by expression of phenotypic markers related to their specialised functions in vivo. World J. Gastroenterol. 12, 5429–5439 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Schluter, K. Et al. Organ-specific metastatic tumor cell adhesion and extravasation of colon carcinoma cells with different metastatic potential. Am. J. Pathol. 169, 1064–1073 (2006).

    PubMed  PubMed Central  Google Scholar 

  • Brown, D. M. & Ruoslahti, E. Metadherin, a cell surface protein in breast tumors that mediates lung metastasis. Cancer Cell 5, 365–374 (2004). Using phage-display libraries — a technology that had previously allowed this group to identify tissue-specific vasculature differences (or 'zipcodes') — this paper identifies metadherin as a lung-specific homing molecule.

    CAS  PubMed  Google Scholar 

  • Kopp, H. G., Avecilla, S. T., Hooper, A. T. & Rafii, S. The bone marrow vascular niche: home of HSC differentiation and mobilization. Physiology 20, 349–356 (2005).

    CAS  PubMed  Google Scholar 

  • Weis, S., Cui, J., Barnes, L. & Cheresh, D. Endothelial barrier disruption by VEGF-mediated Src activity potentiates tumor cell extravasation and metastasis. J. Cell Biol. 167, 223–229 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gupta, G. P. Et al. Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446, 765–770 (2007).

    CAS  PubMed  Google Scholar 

  • Karnoub, A. E. Et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature 449, 557–563 (2007).

    CAS  PubMed  Google Scholar 

  • Padua, D. Et al. TGFβ primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133, 66–77 (2008). References 62 and 63 exemplify how paracrine signals from the stroma of a primary tumour can stimulate departing cancer cells to extravasate into the lung without affecting primary tumorigenesis.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, H. Et al. Tumor cell α3β1 integrin and vascular laminin-5 mediate pulmonary arrest and metastasis. J. Cell Biol. 164, 935–941 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Weil, R. J., Palmieri, D. C., Bronder, J. L., Stark, A. M. & Steeg, P. S. Breast cancer metastasis to the central nervous system. Am. J. Pathol. 167, 913–920 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Minn, A. J. Et al. Lung metastasis genes couple breast tumor size and metastatic spread. Proc. Natl Acad. Sci. USA 104, 6740–6745 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Smid, M. Et al. Genes associated with breast cancer metastatic to bone. J. Clin. Oncol. 24, 2261–2267 (2006).

    CAS  PubMed  Google Scholar 

  • Nesbitt, J. C., Putnam, J. B. Jr, Walsh, G. L., Roth, J. A. & Mountain, C. F. Survival in early-stage non-small cell lung cancer. Ann. Thorac. Surg. 60, 466–472 (1995).

    CAS  PubMed  Google Scholar 

  • Ries, L. A. G. Et al. SEER Cancer Statistics Review, 1975–2005 National Cancer Institute [online] http://seer.Cancer.Gov/csr/1975_2005/index.Html (2008)

    Google Scholar 

  • Janne, P. A. Et al. Twenty-five years of clinical research for patients with limited-stage small cell lung carcinoma in North America. Cancer 95, 1528–1538 (2002).

    PubMed  Google Scholar 

  • Briele, H. A. & Das Gupta, T. K. Natural history of cutaneous malignant melanoma. World J. Surg. 3, 255–270 (1979).

    CAS  PubMed  Google Scholar 

  • Sorlie, T. Et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl Acad. Sci. USA 98, 10869–10874 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Garraway, L. A. Et al. Integrative genomic analyses identify MITF as a lineage survival oncogene amplified in malignant melanoma. Nature 436, 117–122 (2005).

    CAS  PubMed  Google Scholar 

  • Gupta, P. B. Et al. The melanocyte differentiation program predisposes to metastasis after neoplastic transformation. Nature Genet. 37, 1047–1054 (2005).

    CAS  PubMed  Google Scholar 

  • Wong, D. J. Et al. Module map of stem cell genes guides creation of epithelial cancer stem cells. Cell Stem Cell 2, 333–344 (2008). This study shows an association between the expression of embryonic stem cell gene modules in primary tumours and increased metastatic potential.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Varambally, S. Et al. The polycomb group protein EZH2 is involved in progression of prostate cancer. Nature 419, 624–629 (2002).

    CAS  PubMed  Google Scholar 

  • Kleer, C. G. Et al. EZH2 is a marker of aggressive breast cancer and promotes neoplastic transformation of breast epithelial cells. Proc. Natl Acad. Sci. USA 100, 11606–11611 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Varambally, S. Et al. Genomic loss of microRNA-101 leads to overexpression of histone methyltransferase EZH2 in cancer. Science 322, 1695–1699 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Gregory, P. A. Et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nature Cell Biol. 10, 593–601 (2008).

    CAS  PubMed  Google Scholar 

  • Ma, L., Teruya-Feldstein, J. & Weinberg, R. A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449, 682–688 (2007).

    CAS  PubMed  Google Scholar 

  • Demicheli, R. Tumour dormancy: findings and hypotheses from clinical research on breast cancer. Semin. Cancer Biol. 11, 297–306 (2001).

    CAS  PubMed  Google Scholar 

  • Braun, S. Et al. Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N. Engl. J. Med. 342, 525–533 (2000).

    CAS  PubMed  Google Scholar 

  • Husemann, Y. Et al. Systemic spread is an early step in breast cancer. Cancer Cell 13, 58–68 (2008). This paper shows that dissemination of tumour cells can occur at early stages of primary tumour development in ERBB2 and PyMT mouse models. Moreover, transplantation of pre-malignant DTCs into recipient bone marrow releases these cells from dormancy.

    PubMed  Google Scholar 

  • White, D. E. Et al. Targeted disruption of β1-integrin in a transgenic mouse model of human breast cancer reveals an essential role in mammary tumor induction. Cancer Cell 6, 159–170 (2004).

    CAS  PubMed  Google Scholar 

  • Aguirre-Ghiso, J. A., Estrada, Y., Liu, D. & Ossowski, L. ERKMAPK activity as a determinant of tumor growth and dormancy; regulation by p38SAPK. Cancer Res. 63, 1684–1695 (2003).

    CAS  PubMed  Google Scholar 

  • Aguirre-Ghiso, J. A., Ossowski, L. & Rosenbaum, S. K. Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth. Cancer Res. 64, 7336–7345 (2004).

    CAS  PubMed  Google Scholar 

  • Nash, K. T. Et al. Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. J. Natl Cancer Inst. 99, 309–321 (2007).

    CAS  PubMed  Google Scholar 

  • Xu, L., Begum, S., Hearn, J. D. & Hynes, R. O. GPR56, an atypical G protein-coupled receptor, binds tissue transglutaminase, TG2, and inhibits melanoma tumor growth and metastasis. Proc. Natl Acad. Sci. USA 103, 9023–9028 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park, Y. G. Et al. Sipa1 is a candidate for underlying the metastasis efficiency modifier locus Mtes1. Nature Genet. 37, 1055–1062 (2005).

    CAS  PubMed  Google Scholar 

  • Holmgren, L., O'Reilly, M. S. & Folkman, J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nature Med. 1, 149–153 (1995).

    CAS  PubMed  Google Scholar 

  • Almog, N. Et al. Transcriptional switch of dormant tumors to fast-growing angiogenic phenotype. Cancer Res. 69, 836–844 (2009).

    CAS  PubMed  Google Scholar 

  • Naumov, G. N., Akslen, L. A. & Folkman, J. Role of angiogenesis in human tumor dormancy: animal models of the angiogenic switch. Cell Cycle 5, 1779–1787 (2006).

    CAS  PubMed  Google Scholar 

  • Luzzi, K. J. Et al. Multistep nature of metastatic inefficiency: dormancy of solitary cells after successful extravasation and limited survival of early micrometastases. Am. J. Pathol. 153, 865–873 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Becker, S., Becker-Pergola, G., Wallwiener, D., Solomayer, E. F. & Fehm, T. Detection of cytokeratin-positive cells in the bone marrow of breast cancer patients undergoing adjuvant therapy. Breast Cancer Res. Treat. 97, 91–96 (2006).

    CAS  PubMed  Google Scholar 

  • Ling, L. J. Et al. A novel mouse model of human breast cancer stem-like cells with high CD44+CD24−/lower phenotype metastasis to human bone. Chin. Med. J. 121, 1980–1986 (2008).

    CAS  PubMed  Google Scholar 

  • Gupta, G. P. Et al. ID genes mediate tumor reinitiation during breast cancer lung metastasis. Proc. Natl Acad. Sci. USA 104, 19506–19511 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Swarbrick, A., Roy, E., Allen, T. & Bishop, J. M. Id1 cooperates with oncogenic Ras to induce metastatic mammary carcinoma by subversion of the cellular senescence response. Proc. Natl Acad. Sci. USA 105, 5402–5407 (2008).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Park, B. K. Et al. NF-κB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nature Med. 13, 62–69 (2007).

    CAS  PubMed  Google Scholar 

  • Fitzgerald, D. P. Et al. Reactive glia are recruited by highly proliferative brain metastases of breast cancer and promote tumor cell colonization. Clin. Exp. Metastasis 25, 799–810 (2008).

    PubMed  PubMed Central  Google Scholar 

  • Sharma, S. V., Bell, D. W., Settleman, J. & Haber, D. A. Epidermal growth factor receptor mutations in lung cancer. Nature Rev. Cancer 7, 169–181 (2007).

    CAS  Google Scholar 

  • Engelman, J. A. Et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling. Science 316, 1039–1043 (2007).

    CAS  PubMed  Google Scholar 

  • Bean, J. Et al. MET amplification occurs with or without T790M mutations in EGFR mutant lung tumors with acquired resistance to gefitinib or erlotinib. Proc. Natl Acad. Sci. USA 104, 20932–20937 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  • Aragon-Ching, J. B. & Zujewski, J. A. CNS metastasis: an old problem in a new guise. Clin. Cancer Res. 13, 1644–1647 (2007).

    CAS  PubMed  Google Scholar 

  • Fidler, I. J., Yano, S., Zhang, R. D., Fujimaki, T. & Bucana, C. D. The seed and soil hypothesis: vascularisation and brain metastases. Lancet Oncol. 3, 53–57 (2002).

    CAS  PubMed  Google Scholar 

  • Wiedswang, G. Et al. Isolated tumor cells in bone marrow three years after diagnosis in disease-free breast cancer patients predict unfavorable clinical outcome. Clin. Cancer Res. 10, 5342–5348 (2004).

    PubMed  Google Scholar 

  • Popular posts from this blog