Top

Journal of Cancer Research and Clinical Oncology

Published in:

01-10-2013 | Review

Tumor promoters: from chemicals to inflammatory proteins

Authors: Hirota Fujiki, Eisaburo Sueoka, Masami Suganuma

Published in: Journal of Cancer Research and Clinical Oncology | Issue 10/2013

Abstract

Purpose

The classic two-stage chemical carcinogenesis in rodents is not directly linked to multistage carcinogenesis in humans. In light of our findings that tumor necrosis factor-α (TNF-α) is an endogenous tumor promoter and that TNF-α-inducing protein (Tipα) of Helicobacter pylori stimulates progression of cancer and epithelial–mesenchymal transition, we think it is necessary to re-examine the concept of tumor promoter, from chemicals to inflammatory proteins.

Topics and results

This paper begins with “inflammation,” discovered by Virchow, studies of Yamagiwa and Tsutsui, and briefly reviews numerous topics, such as (1) the classic concept of tumor promoter, (2) tumor promotion on mouse skin induced by protein kinase C activators and okadaic acid class compounds, (3) organ specificity of tumor promoters, presenting numerous tumor promoters in various organs, (4) unique tumor promotion induced by inhibitors of protein phosphatases 1 and 2A in mouse skin, rat glandular stomach, and rat liver, (5) the significant role of TNF-α in tumor-promoting inflammation, (6) progression induced by Tipα of H. pylori, and (7) enhancement of cancer treatment efficacy with the combination of anticancer drugs and green tea catechins, to inhibit tumor-promoting inflammation.

Conclusion

Human cancer development involves both durable genetic changes caused by carcinogens and proinflammatory cytokines, and simultaneous inflammation in progression induced by proinflammatory cytokines and chemokines.

Acharyya S, Oskarsson T, Vanharanta S, Malladi S, Kim J, Morris PG, Manova-Todorova K, Leversha M, Hogg N, Seshan VE, Norton L, Brogi E, Massague J (2012) A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150(1):165–178PubMedCrossRef

Balmain A, Pragnell IB (1983) Mouse skin carcinomas induced in vivo by chemical carcinogens have a transforming Harvey-ras oncogene. Nature 303(5912):72–74PubMedCrossRef

Berenblum I (1941) The cocarcinogenic action of croton resin. Cancer Res 1:44–50

Berenblum I, Shubik P (1947) A new, quantitative, approach to the study of the stages of chemical carcinogenesis in the mouse’s skin. Br J Cancer 1(4):383–391PubMedCrossRef

Boutwell RK (1977) The role of the induction of ornithine decarboxylase in tumor promotion. In: Hiatt HH, Watson JD, Winsten JA (eds) Origin of human cancer. Cold Spring Harbor Laboratory, Cold Spring Harbor, pp 773–783

Bruchard M, Mignot G, Derangere V, Chalmin F, Chevriaux A, Vegran F, Boireau W, Simon B, Ryffel B, Connat JL, Kanellopoulos J, Martin F, Rebe C, Apetoh L, Ghiringhelli F (2013) Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth. Nat Med 19(1):57–64PubMedCrossRef

Castagna M, Takai Y, Kaibuchi K, Sano K, Kikkawa U, Nishizuka Y (1982) Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem 257(13):7847–7851PubMed

Coulon S, Francque S, Colle I, Verrijken A, Blomme B, Heindryckx F, De Munter S, Prawitt J, Caron S, Staels B, Van Vlierberghe H, Van Gaal L, Geerts A (2012) Evaluation of inflammatory and angiogenic factors in patients with non-alcoholic fatty liver disease. Cytokine 59(2):442–449PubMedCrossRef

Daff ME, Doll R, Kennaway EL (1951) Cancer of the lung in relation to tobacco. Br J Cancer 5(1):1–20PubMedCrossRef

Delclos KB, Nagle DS, Blumberg PM (1980) Specific binding of phorbol ester tumor promoters to mouse skin. Cell 19(4):1025–1032PubMedCrossRef

Delclos KB, Yeh E, Blumberg PM (1983) Specific labeling of mouse brain membrane phospholipids with [20-³H]phorbol 12-p-azidobenzoate 13-benzoate, a photolabile phorbol ester. Proc Natl Acad Sci USA 80(10):3054–3058PubMedCrossRef

DiGiovanni J (1992) Multistage carcinogenesis in mouse skin. Pharmacol Ther 54(1):63–128PubMedCrossRef

Duda JE, Lee VM, Trojanowski JQ (2000) Neuropathology of synuclein aggregates. J Neurosci Res 61(2):121–127PubMedCrossRef

Endo Y, Shudo K, Okamoto T (1982) Molecular requirements for epigenetic modulators. Synthesis of active fragments of teleocidins and lyngbyatoxin. Chem Pharm Bull 30:3457–3460CrossRef

Fibiger J (1965) Investigations on spiroptera carcinoma and the experimental induction of cancer. In: The Nobel Foundation (ed) Nobel lectures including presentation speeches and laureates’biographies, physiology or medicine 1922–1941. Elsevier Publishing Company, Amsterdam-London-New York, pp 122–150

Fujiki H, Suganuma M (1993) Tumor promotion by inhibitors of protein phosphatases 1 and 2A: the okadaic acid class of compounds. Adv Cancer Res 61:143–194PubMedCrossRef

Fujiki H, Suganuma M (1994) Tumor necrosis factor-α a new tumor promoter, engendered by biochemical studies of okadaic acid. J Biochem (Tokyo) 115(1):1–5

Fujiki H, Suganuma M (2011) Tumor promoters—microcystin-LR, nodularin and TNF-α and human cancer development. Anticancer Agents Med Chem 11:4–18PubMedCrossRef

Fujiki H, Suganuma M (2012) Green tea: an effective synergist with anticancer drugs for tertiary cancer prevention. Cancer Lett 324(2):119–125PubMedCrossRef

Fujiki H, Sugimura T (1987) New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin. Adv Cancer Res 49:223–264PubMedCrossRef

Fujiki H, Mori M, Nakayasu M, Terada M, Sugimura T, Moore RE (1981) Indole alkaloids: dihydroteleocidin B, teleocidin, and lyngbyatoxin A as members of a new class of tumor promoters. Proc Natl Acad Sci USA 78(6):3872–3876PubMedCrossRef

Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (1984a) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU Science Press, Tokyo/Utrecht

Fujiki H, Suganuma M, Tahira T, Yoshioka A, Nakayasu M, Endo Y, Shudo K, Takayama S, Moore RE, Sugimura T (1984b) Nakahara memorial lecture. New classes of tumor promoters: teleocidin, aplysiatoxin, and palytoxin. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU Science Press, Tokyo/Utrecht, pp 37–45

Fujiki H, Tanaka Y, Miyake R, Kikkawa U, Nishizuka Y, Sugimura T (1984c) Activation of calcium-activated, phospholipid-dependent protein kinase (protein kinase C) by new classes of tumor promoters: teleocidin and debromoaplysiatoxin. Biochem Biophys Res Commun 120(2):339–343PubMedCrossRef

Fujiki H, Suganuma M, Yoshizawa S, Kanazawa H, Sugimura T, Manam S, Kahn SM, Jiang W, Hoshina S, Weinstein IB (1989) Codon 61 mutations in the c-Harvey-ras gene in mouse skin tumors induced by 7,12-dimethylbenz[a]anthracene plus okadaic acid class tumor promoters. Mol Carcinog 2(4):184–187PubMedCrossRef

Fujiki H, Suganuma M, Okabe S, Sueoka E, Suga K, Imai K, Nakachi K (2000) A new concept of tumor promotion by tumor necrosis factor-α, and cancer preventive agents (-)-epigallocatechin gallate and green tea—A review. Cancer Detect Prev 24(1):91–99PubMed

Fujiki H, Suganuma M, Imai K, Nakachi K (2002) Green tea: cancer preventive beverage and/or drug. Cancer Lett 188:9–13PubMedCrossRef

Fujiki H, Imai K, Nakachi K, Shimizu M, Moriwaki H, Suganuma M (2012a) Challenging the effectiveness of green tea in primary and tertiary cancer prevention. J Cancer Res Clin Oncol 138(8):1259–1270PubMedCrossRef

Fujiki H, Watanabe T, Suganuma M (2012b) Tumor promotion by TNF-α-inducing protein and its receptor nucleolin in human gastric carcinogenesis by Helicobacter pylori. Trends Cancer Res 8:97–117

Fukushima S, Friedell GH, Jacobs JB, Cohen SM (1981) Effect of l-tryptophan and sodium saccharin on urinary tract carcinogenesis initiated by N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide. Cancer Res 41(8):3100–3103PubMed

Guy GR, Cao X, Chua SP, Tan YH (1992) Okadaic acid mimics multiple changes in early protein phosphorylation and gene expression induced by tumor necrosis factor or interleukin-1. J Biol Chem 267(3):1846–1852PubMed

Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674PubMedCrossRef

Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297(5580):353–356PubMedCrossRef

Hecker E (1967) Phorbol esters from croton oil, chemical nature and biological activities. Naturwissenschaften 54(11):282–284PubMedCrossRef

Hecker E, Adolf W, Hergenhahn R, Schmidt R, Sorg B (1984) Irritant diterpene ester promoters of mouse skin: contributions to etiologies of environmental cancer and to biochemical mechanisms of carcinogenesis. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU Science Press, Tokyo/Utrecht, pp 3–36

Hennings H, Shores R, Wenk ML, Spangler EF, Tarone R, Yuspa SH (1983) Malignant conversion of mouse skin tumours is increased by tumour initiators and unaffected by tumour promoters. Nature 304(5921):67–69PubMedCrossRef

Itai A, Kato Y, Tomioka N, Iitaka Y, Endo Y, Hasegawa M, Shudo K, Fujiki H, Sakai S (1988) A receptor model for tumor promoters: rational superposition of teleocidins and phorbol esters. Proc Natl Acad Sci USA 85(11):3688–3692PubMedCrossRef

Ito N, Fukushima S, Tsuda H, Shirai T, Tatematsu M, Imaida K (1984) Modification of chemical carcinogenesis by antioxidants. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU/Science Press, Tokyo/Utrecht, pp 381–389

Kakizoe T, Nishio Y, Honma Y, Niijima T, Sugimura T (1984) l-isoleucine and l-leucine are promoters of bladder cancer in rats. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU Science Press, Tokyo/Utrecht, pp 373–380

Kishimoto T (1989) The biology of interleukin-6. Blood 74(1):1–10PubMed

Kitagawa T, Sugano H (1978) Enhancing effect of phenobarbital on the development of enzyme-altered islands and hepatocellular carcinomas initiated by 3′-methyl-4-(dimethylamino)azobenzene or diethylnitrosamine. Gann 69:679–689PubMed

Kitagawa T, Kayano T, Mikami K, Watanabe R, Sugano H (1984) Promotion of hepatocarcinogenesis in vivo and in vitro. In: Fujiki H, Hecker E, Moore RE, Sugimura T, Weinstein IB (eds) Cellular interactions by environmental tumor promoters. Jpn Sci Soc Press/VNU Science Press, Tokyo/Utrecht, pp 337–348

Komori A, Yatsunami J, Suganuma M, Okabe S, Abe S, Sakai A, Sasaki K, Fujiki H (1993) Tumor necrosis factor acts as a tumor promoter in BALB/3T3 cell transformation. Cancer Res 53(9):1982–1985PubMed

Mottram JC (1944) A developing factor in experimental blastogenesis. J Pathol Bacteriol 56:181–187CrossRef

Nakamura A, Shirai T, Ogawa K, Wada S, Fujimoto NA, Ito A, Ito N (1990) Promoting action of prolactin released from a grafted transplantable pituitary tumor (MtT/F84) on rat prostate carcinogenesis. Cancer Lett 53(2–3):151–157PubMedCrossRef

Nishiwaki-Matsushima R, Ohta T, Nishiwaki S, Suganuma M, Kohyama K, Ishikawa T, Carmichael WW, Fujiki H (1992) Liver tumor promotion by the cyanobacterial cyclic peptide toxin microcystin-LR. J Cancer Res Clin Oncol 118(6):420–424PubMedCrossRef

Nishizuka Y (1984) The role of protein kinase C in cell surface signal transduction and tumour promotion. Nature 308(5961):693–698PubMedCrossRef

Noach LA, Bosma NB, Jansen J, Hoek FJ, van Deventer SJ, Tytgat GN (1994) Mucosal tumor necrosis factor-α, interleukin-1β, and interleukin-8 production in patients with Helicobacter pylori infection. Scand J Gastroenterol 29(5):425–429PubMedCrossRef

Ohta T, Sueoka E, Iida N, Komori A, Suganuma M, Nishiwaki R, Tatematsu M, Kim SJ, Carmichael WW, Fujiki H (1994) Nodularin, a potent inhibitor of protein phosphatases 1 and 2A, is a new environmental carcinogen in male F344 rat liver. Cancer Res 54(24):6402–6406PubMed

Peraino C, Fry RJM, Staffeldt E (1971) Reduction and enhancement by phenobarbital of hepatocarcinogenesis induced in the rat by 2-acetylaminofluorene. Cancer Res 31(10):1506–1512PubMed

Schmidt R, Sorg B, Marston A, Hecker E (1983) Bivalent and photoaffinity-labeled ligands to study specific binding sites of phorbol esters in mouse epidermis. J Cancer Res Clin Oncol 105:A26

Sen R, Baltimore D (1986) Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell 46(5):705–716PubMedCrossRef

Shimizu N, Inada K, Nakanishi H, Tsukamoto T, Ikehara Y, Kaminishi M, Kuramoto S, Sugiyama A, Katsuyama T, Tatematsu M (1999) Helicobacter pylori infection enhances glandular stomach carcinogenesis in Mongolian gerbils treated with chemical carcinogens. Carcinogenesis 20(4):669–676PubMedCrossRef

Shimizu M, Fukutomi Y, Ninomiya M, Nagura K, Kato T, Araki H, Suganuma M, Fujiki H, Moriwaki H (2008) Green tea extracts for the prevention of metachronous colorectal adenomas: a pilot study. Cancer Epidemiol Biomarkers Prev 17(11):3020–3025PubMedCrossRef

Shurin MR (2013) Dual role of immunomodulation by anticancer chemotherapy. Nat Med 19(1):20–22PubMedCrossRef

Somers-Edgar TJ, Scandlyn MJ, Stuart EC, Le Nedelec MJ, Valentine SP, Rosengren RJ (2008) The combination of epigallocatechin gallate and curcumin suppresses ERα-breast cancer cell growth in vitro and in vivo. Int J Cancer 122(9):1966–1971PubMedCrossRef

Stearns ME, Wang M (2011) Synergistic effects of the green tea extract epigallocatechin-3-gallate and taxane in eradication of malignant human prostate tumors. Transl Oncol 4(3):147–156PubMed

Sueoka E, Sueoka N, Okabe S, Kozu T, Komori A, Ohta T, Suganuma M, Kim SJ, Lim IK, Fujiki H (1997) Expression of the tumor necrosis factor-α gene and early response genes by nodularin, a liver tumor promoter, in primary cultured rat hepatocytes. J Cancer Res Clin Oncol 123(8):413–419PubMed

Suganuma M, Fujiki H, Suguri H, Yoshizawa S, Hirota M, Nakayasu M, Ojika M, Wakamatsu K, Yamada K, Sugimura T (1988) Okadaic acid: an additional non-phorbol-12-tetradecanoate-13-acetate-type tumor promoter. Proc Natl Acad Sci USA 85(6):1768–1771PubMedCrossRef

Suganuma M, Fujiki H, Okabe S, Nishiwaki S, Brautigan D, Ingebritsen TS, Rosner MR (1992a) Structurally different members of the okadaic acid class selectively inhibit protein serine/threonine but not tyrosine phosphatase activity. Toxicon 30(8):873–878PubMedCrossRef

Suganuma M, Tatematsu M, Yatsunami J, Yoshizawa S, Okabe S, Uemura D, Fujiki H (1992b) An alternative theory of tissue specificity by tumor promotion of okadaic acid in glandular stomach of SD rats. Carcinogenesis 13(10):1841–1845PubMedCrossRef

Suganuma M, Yatsunami J, Yoshizawa S, Okabe S, Fujiki H (1993) Absence of synergistic effects on tumor promotion in CD-1 mouse skin by simultaneous applications of two different types of tumor promoters, okadaic acid and teleocidin. Cancer Res 53(5):1012–1016PubMed

Suganuma M, Okabe S, Marino MW, Sakai A, Sueoka E, Fujiki H (1999) Essential role of tumor necrosis factor α (TNF-α) in tumor promotion as revealed by TNF-α-deficient mice. Cancer Res 59(18):4516–4518PubMed

Suganuma M, Kurusu M, Okabe S, Sueoka N, Yoshida M, Wakatsuki Y, Fujiki H (2001) Helicobacter pylori membrane protein 1: a new carcinogenic factor of Helicobacter pylori. Cancer Res 61(17):6356–6359PubMed

Suganuma M, Okabe S, Kurusu M, Iida N, Ohshima S, Saeki Y, Kishimoto T, Fujiki H (2002) Discrete roles of cytokines, TNF-α, IL-1, IL-6 in tumor promotion and cell transformation. Int J Oncol 20(1):131–136PubMed

Suganuma M, Kurusu M, Suzuki K, Nishizono A, Murakami K, Fujioka T, Fujiki H (2005) New tumor necrosis factor-α-inducing protein released from Helicobacter pylori for gastric cancer progression. J Cancer Res Clin Oncol 131(5):305–313PubMedCrossRef

Suganuma M, Yamaguchi K, Ono Y, Matsumoto H, Hayashi T, Ogawa T, Imai K, Kuzuhara T, Nishizono A, Fujiki H (2008) TNF-α-inducing protein, a carcinogenic factor secreted from H. pylori, enters gastric cancer cells. Int J Cancer 123(1):117–122PubMedCrossRef

Suganuma M, Saha A, Fujiki H (2011) New cancer treatment strategy using combination of green tea catechins and anticancer drugs. Cancer Sci 102(2):317–323PubMedCrossRef

Suganuma M, Watanabe T, Yamaguchi K, Takahashi A, Fujiki H (2012) Human gastric cancer development with TNF-α-inducing protein secreted from Helicobacter pylori. Cancer Lett 322(2):133–138PubMedCrossRef

Takahashi M, Hasegawa R, Furukawa F, Toyoda K, Sato H, Hayashi Y (1986) Effects of ethanol, potassium metabisulfite, formaldehyde and hydrogen peroxide on gastric carcinogenesis in rats after initiation with N-methyl-N’-nitro-N-nitrosoguanidine. Jpn J Cancer Res 77(2):118–124PubMed

Takai A, Bialojan C, Troschka M, Ruegg JC (1987) Smooth muscle myosin phosphatase inhibition and force enhancement by black sponge toxin. FEBS Lett 217(1):81–84PubMedCrossRef

Thévenin C, Kim SJ, Rieckmann P, Fujiki H, Norcross MA, Sporn MB, Fauci AS, Kehrl JH (1990) Induction of nuclear factor-κB and the human immunodeficiency virus long terminal repeat by okadaic acid, a specific inhibitor of phosphatases 1 and 2A. New Biol 2(9):793–800PubMed

Topping DC, Nettesheim P (1980) Two-stage carcinogenesis studies with asbestos in Fischer 344 rats. J Natl Cancer Inst 65:627–630PubMed

Tsutsui H (1918) Über das künstlich erzeugte Cancroid bei der Maus. Gann 1(XII): 17–21

Van Duuren BL (1969) Tumor-promoting agents in two-stage carcinogenesis. Prog Exp Tumor Res 11:31–68PubMed

Virchow R (1858) Reizung und Reizbarkeit. Arch pathol Anat u Physiol u klin Medizin 14:1–63CrossRef

Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319(9):525–532PubMedCrossRef

Watanabe K, Reddy BS, Wong CQ, Weisburger JH (1978) Effect of dietary undegraded carrageenan on colon carcinogenesis in F344 rats treated with azoxymethane or methylnitrosourea. Cancer Res 38(12):4427–4430PubMed

Watanabe T, Tsuge H, Imagawa T, Kise D, Hirano K, Beppu M, Takahashi A, Yamaguchi K, Fujiki H, Suganuma M (2010) Nucleolin as cell surface receptor for tumor necrosis factor-α inducing protein: a carcinogenic factor of Helicobacter pylori. J Cancer Res Clin Oncol 136(6):911–921PubMedCrossRef

Yamagiwa K, Ichikawa K (1915) Experimentelle Studie über die Pathogenese der Epithelialgeschwülste. Mitteilungen Med Fakultät Kaiserl Univ Tokyo 15:295–344

Yoshida T (1956) Cancer research in Japan. Cancer Res 16(11):1007–1008PubMed

Yoshida M, Wakatsuki Y, Kobayashi Y, Itoh T, Murakami K, Mizoguchi A, Usui T, Chiba T, Kita T (1999) Cloning and characterization of a novel membrane-associated antigenic protein of Helicobacter pylori. Infect Immun 67(1):286–293PubMed

Yoshizawa S, Matsushima R, Watanabe MF, Harada K, Ichihara A, Carmichael WW, Fujiki H (1990) Inhibition of protein phosphatases by microcystins and nodularin associated with hepatotoxicity. J Cancer Res Clin Oncol 116(6):609–614PubMedCrossRef

Title: Tumor promoters: from chemicals to inflammatory proteins
Authors: Hirota Fujiki
Eisaburo Sueoka
Masami Suganuma
Publication date: 01-10-2013
Publisher: Springer Berlin Heidelberg
Published in: Journal of Cancer Research and Clinical Oncology / Issue 10/2013
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-013-1455-8

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Tumor promoters: from chemicals to inflammatory proteins

Abstract

Purpose

Topics and results

Conclusion

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Topics and results

Conclusion

Please log in to get access to this content

Other articles of this Issue 10/2013

Autoantibody biomarkers identified by proteomics methods distinguish ovarian cancer from non-ovarian cancer with various CA-125 levels

Rituximab, Ara-C, dexamethasone and oxaliplatin (R-ADOx) is effective for treatment of elderly patients with relapsed mantle cell lymphoma

A modified TNM-7 staging system to better predict the survival in patients with hepatocellular carcinoma after hepatectomy

Cetuximab-induced skin exanthema: prophylactic and reactive skin therapy are equally effective

Erratum to: Prognostic factors of metastatic renal cell carcinoma with extensive sarcomatoid component

Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in patients with EGFR mutation-positive lung adenocarcinoma

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page