Skip to main content
Top
Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats

Published in: BMC Cancer | Issue 1/2016

Login to get access

Abstract

Background

The occurrence of cancer during pregnancy merges two complex, poorly understood metabolic and hormonal conditions. This association can exacerbate the conditions of both the mother and the foetus. The branched-chain amino acid leucine enhances cellular activity, particularly by increasing protein synthesis. This study aimed to analyse the modulatory effect of a leucine-rich diet on direct and indirect tumour-induced placental damage. This was accomplished by evaluating the expression of genes involved in protein synthesis and degradation and assessing anti-oxidant enzyme activity in placental tissues collected from pregnant, tumour-bearing rats.

Results

Pregnant rats were either implanted with Walker 256 tumour cells or injected with ascitic fluid (to study the indirect effects of tumour growth) and then fed a leucine-rich diet. Animals in a control group underwent the same procedures but were fed a normal diet. On the 20th day of pregnancy, tumour growth was observed. Dams fed a normoprotein diet showed the greatest tumour growth. Injection with ascitic fluid mimicked the effects of tumour growth. Decreased placental protein synthesis and increased protein degradation were observed in both the tumour-bearing and the ascitic fluid-injected groups that were fed a normoprotein diet. These effects resulted in low placental DNA and protein content and high lipid peroxidation (measured by malondialdehyde content). Decreased placental protein synthesis-related gene expression was observed in the tumour group concomitant with increased expression of genes encoding protein degradation-associated proteins and proteolytic subunits.

Conclusions

Consumption of a leucine-rich diet counteracted the effects produced by tumour growth and injection with ascitic fluid. The diet enhanced cell signalling, ameliorated deficiencies in DNA and protein content, and balanced protein synthesis and degradation processes in the placenta. The improvements in cell signalling included changes in the mTOR/eIF pathway. In conclusion, consumption of a leucine-rich diet improved placental metabolism and cell signalling in tumour-bearing rats, and these changes reduced the deleterious effects caused by tumour growth.
Literature
1.
go back to reference Cruz B, Gomes-Marcondes MCC. Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour. Reprod Biol Endocrinol. 2014;12:2.PubMedCentralCrossRefPubMed Cruz B, Gomes-Marcondes MCC. Leucine-rich diet supplementation modulates foetal muscle protein metabolism impaired by Walker-256 tumour. Reprod Biol Endocrinol. 2014;12:2.PubMedCentralCrossRefPubMed
2.
go back to reference Viana LR, Gomes-Marcondes MCC. Leucine-rich diet improves the serum amino acid profile and body composition of fetuses from tumor-bearing pregnant mice. Biol Reprod. 2013;88:121.CrossRefPubMed Viana LR, Gomes-Marcondes MCC. Leucine-rich diet improves the serum amino acid profile and body composition of fetuses from tumor-bearing pregnant mice. Biol Reprod. 2013;88:121.CrossRefPubMed
3.
go back to reference Azim Jr HA, Peccatori FA, Pavlidis N. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part II: Hematological tumors. Cancer Treat Rev. 2010;36:110–21.CrossRefPubMed Azim Jr HA, Peccatori FA, Pavlidis N. Treatment of the pregnant mother with cancer: a systematic review on the use of cytotoxic, endocrine, targeted agents and immunotherapy during pregnancy. Part II: Hematological tumors. Cancer Treat Rev. 2010;36:110–21.CrossRefPubMed
4.
go back to reference Pavlidis N, Pentheroudakis G. The pregnant mother with breast cancer: diagnostic and therapeutic management. Cancer Treat Rev. 2005;31:439–47.CrossRefPubMed Pavlidis N, Pentheroudakis G. The pregnant mother with breast cancer: diagnostic and therapeutic management. Cancer Treat Rev. 2005;31:439–47.CrossRefPubMed
5.
go back to reference Azim Jr HA, Brohee S, Peccatori FA, Desmedt C, Loi S, Lambrechts D, et al. Biology of breast cancer during pregnancy using genomic profiling. Endocr Relat Cancer. 2014;21:545–54.CrossRefPubMed Azim Jr HA, Brohee S, Peccatori FA, Desmedt C, Loi S, Lambrechts D, et al. Biology of breast cancer during pregnancy using genomic profiling. Endocr Relat Cancer. 2014;21:545–54.CrossRefPubMed
6.
go back to reference Peccatori FA, Azim Jr HA, Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(6):vi160–70.PubMed Peccatori FA, Azim Jr HA, Orecchia R, Hoekstra HJ, Pavlidis N, Kesic V, et al. Cancer, pregnancy and fertility: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(6):vi160–70.PubMed
7.
go back to reference Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Burke B, Sutcliffe SB, et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obs Gynecol. 1992;166:781–7.CrossRef Zemlickis D, Lishner M, Degendorfer P, Panzarella T, Burke B, Sutcliffe SB, et al. Maternal and fetal outcome after breast cancer in pregnancy. Am J Obs Gynecol. 1992;166:781–7.CrossRef
8.
go back to reference King RM, Welch JS, Martin Jr JK, Coulam CB. Carcinoma of the breast associated with pregnancy. Surg Gynecol Obs. 1985;160:228–32. King RM, Welch JS, Martin Jr JK, Coulam CB. Carcinoma of the breast associated with pregnancy. Surg Gynecol Obs. 1985;160:228–32.
9.
go back to reference King JC. Physiology of pregnancy and nutrient metabolism. Am J Clin Nutr. 2000;71(5 Suppl):1218S–25S.PubMed King JC. Physiology of pregnancy and nutrient metabolism. Am J Clin Nutr. 2000;71(5 Suppl):1218S–25S.PubMed
10.
11.
go back to reference Gomes-Marcondes MCC, Curi R, CL. Consequences of Walker 256 tumour growth for the placental/foetal development in rats. Cancer Res Ther Control. 1998;5:277–283. Gomes-Marcondes MCC, Curi R, CL. Consequences of Walker 256 tumour growth for the placental/foetal development in rats. Cancer Res Ther Control. 1998;5:277–283.
12.
go back to reference Vale C, Stewart L, Tierney J, Cancer UKCC for CRNR of. Trends in UK cancer trials: results from the UK Coordinating Committee for Cancer Research National Register of Cancer Trials. Br J Cancer. 2005;92:811–4.PubMedCentralCrossRefPubMed Vale C, Stewart L, Tierney J, Cancer UKCC for CRNR of. Trends in UK cancer trials: results from the UK Coordinating Committee for Cancer Research National Register of Cancer Trials. Br J Cancer. 2005;92:811–4.PubMedCentralCrossRefPubMed
13.
go back to reference Reeves PG. Components of the AIN-93 Diets as Improvements in the AIN-76A Diet. Symp Anim Diets Nutr Toxicol Res. 1997;838–841. Reeves PG. Components of the AIN-93 Diets as Improvements in the AIN-76A Diet. Symp Anim Diets Nutr Toxicol Res. 1997;838–841.
14.
go back to reference Vary TC, Dardevet D, Grizard J, Voisin L, Buffiere C, Denis P, et al. Differential regulation of skeletal muscle protein turnover by insulin and IGF-I after bacteremia. Am J Physiol. 1998;275(4 Pt 1):E584–93.PubMed Vary TC, Dardevet D, Grizard J, Voisin L, Buffiere C, Denis P, et al. Differential regulation of skeletal muscle protein turnover by insulin and IGF-I after bacteremia. Am J Physiol. 1998;275(4 Pt 1):E584–93.PubMed
15.
go back to reference Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed
16.
go back to reference Waalkes TP, Udenfriend S. A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med. 1957;50:733–6.PubMed Waalkes TP, Udenfriend S. A fluorometric method for the estimation of tyrosine in plasma and tissues. J Lab Clin Med. 1957;50:733–6.PubMed
17.
go back to reference Toledo MT, Ventrucci G, Gomes-Marcondes MC. Increased oxidative stress in the placenta tissue and cell culture of tumour-bearing pregnant rats. Placenta. 2011;32:859–64.CrossRefPubMed Toledo MT, Ventrucci G, Gomes-Marcondes MC. Increased oxidative stress in the placenta tissue and cell culture of tumour-bearing pregnant rats. Placenta. 2011;32:859–64.CrossRefPubMed
18.
go back to reference Gomes-Marcondes MCC, Tisdale MJ. Induction of protein catabolism and the ubiquitin-proteasome pathway by mild oxidative stress. Cancer Lett. 2002;180:69–74.CrossRefPubMed Gomes-Marcondes MCC, Tisdale MJ. Induction of protein catabolism and the ubiquitin-proteasome pathway by mild oxidative stress. Cancer Lett. 2002;180:69–74.CrossRefPubMed
19.
go back to reference Gad S. Statistics for toxicologists. In: Hayes AW, editor. Principles and Methods of Toxicology. 5th ed. New York: CRC Press; 2008. p. 369–452. Gad S. Statistics for toxicologists. In: Hayes AW, editor. Principles and Methods of Toxicology. 5th ed. New York: CRC Press; 2008. p. 369–452.
20.
go back to reference Toledo MT, Ventrucci G, Marcondes MCCG. Cancer during pregnancy alters the activity of rat placenta and enhances the expression of cleaved PARP, cytochrome-c and caspase 3. BMC Cancer. 2006;6:168.PubMedCentralCrossRefPubMed Toledo MT, Ventrucci G, Marcondes MCCG. Cancer during pregnancy alters the activity of rat placenta and enhances the expression of cleaved PARP, cytochrome-c and caspase 3. BMC Cancer. 2006;6:168.PubMedCentralCrossRefPubMed
22.
go back to reference Bennani-Baiti N, Walsh D. Animal models of the cancer anorexia-cachexia syndrome. Support Care Cancer. 2011;19:1451–63.CrossRefPubMed Bennani-Baiti N, Walsh D. Animal models of the cancer anorexia-cachexia syndrome. Support Care Cancer. 2011;19:1451–63.CrossRefPubMed
24.
go back to reference Tisdale MJ. Cancer cachexia. Curr Opin Gastroenterol. 1991;389:337–42. Tisdale MJ. Cancer cachexia. Curr Opin Gastroenterol. 1991;389:337–42.
25.
go back to reference Gomes-Marcondes MCC, Ventrucci G, Toledo MT, Cury L, Cooper JC. A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats. Brazilian J Med Biol Res. 2003;36:1589–94.CrossRef Gomes-Marcondes MCC, Ventrucci G, Toledo MT, Cury L, Cooper JC. A leucine-supplemented diet improved protein content of skeletal muscle in young tumor-bearing rats. Brazilian J Med Biol Res. 2003;36:1589–94.CrossRef
26.
go back to reference Ventrucci G, Mello MAR, Gomes-Marcondes MCC. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats. BMC Cancer. 2007;7:42.PubMedCentralCrossRefPubMed Ventrucci G, Mello MAR, Gomes-Marcondes MCC. Leucine-rich diet alters the eukaryotic translation initiation factors expression in skeletal muscle of tumour-bearing rats. BMC Cancer. 2007;7:42.PubMedCentralCrossRefPubMed
27.
go back to reference Ventrucci G, Mello MAR, Gomes-Marcondes MCC. Proteasome activity is altered in skeletal muscle tissue of tumour-bearing rats a leucine-rich diet. Endocr Relat Cancer. 2004;11:887–95.CrossRefPubMed Ventrucci G, Mello MAR, Gomes-Marcondes MCC. Proteasome activity is altered in skeletal muscle tissue of tumour-bearing rats a leucine-rich diet. Endocr Relat Cancer. 2004;11:887–95.CrossRefPubMed
28.
go back to reference Toledo MT, Gomes Marcondes MCC. Placental glycogen metabolism changes during walker tumour growth. Placenta. 2004;25:456–62.CrossRefPubMed Toledo MT, Gomes Marcondes MCC. Placental glycogen metabolism changes during walker tumour growth. Placenta. 2004;25:456–62.CrossRefPubMed
29.
go back to reference Bell AW, Ehrhardt RA. Regulation of placental nutrient transport and implications for fetal growth. Nutr Res Rev. 2002;15:211–30.CrossRefPubMed Bell AW, Ehrhardt RA. Regulation of placental nutrient transport and implications for fetal growth. Nutr Res Rev. 2002;15:211–30.CrossRefPubMed
30.
go back to reference Jones HN, Powell TL, Jansson T. Regulation of placental nutrient transport--a review. Placenta. 2007;28:763–74.CrossRefPubMed Jones HN, Powell TL, Jansson T. Regulation of placental nutrient transport--a review. Placenta. 2007;28:763–74.CrossRefPubMed
31.
go back to reference Jansson N, Rosario FJ, Gaccioli F, Lager S, Jones HN, Roos S, et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab. 2013;98:105–13.PubMedCentralCrossRefPubMed Jansson N, Rosario FJ, Gaccioli F, Lager S, Jones HN, Roos S, et al. Activation of placental mTOR signaling and amino acid transporters in obese women giving birth to large babies. J Clin Endocrinol Metab. 2013;98:105–13.PubMedCentralCrossRefPubMed
32.
go back to reference Proud CG. mTOR-mediated regulation of translation factors by amino acids. Biochem Biophys Res Commun. 2004;313:429–36.CrossRefPubMed Proud CG. mTOR-mediated regulation of translation factors by amino acids. Biochem Biophys Res Commun. 2004;313:429–36.CrossRefPubMed
34.
go back to reference Larqué E, Ruiz-Palacios M, Koletzko B. Placental regulation of fetal nutrient supply. Curr Opin Clin Nutr Metab Care. 2013;16:292–7.CrossRefPubMed Larqué E, Ruiz-Palacios M, Koletzko B. Placental regulation of fetal nutrient supply. Curr Opin Clin Nutr Metab Care. 2013;16:292–7.CrossRefPubMed
35.
go back to reference Biri A, Bozkurt N, Turp A, Kavutcu M, Himmetoglu O, Durak I. Role of oxidative stress in intrauterine growth restriction. Gynecol Obs Invest. 2007;64:187–92.CrossRef Biri A, Bozkurt N, Turp A, Kavutcu M, Himmetoglu O, Durak I. Role of oxidative stress in intrauterine growth restriction. Gynecol Obs Invest. 2007;64:187–92.CrossRef
36.
go back to reference Bulgan Kilicdag E, Ay G, Celik A, Ustundag B, Ozercan I, Simsek M. Oxidant-antioxidant system changes relative to placental-umbilical pathology in patients with preeclampsia. Hypertens Pregnancy. 2005;24:147–57.CrossRefPubMed Bulgan Kilicdag E, Ay G, Celik A, Ustundag B, Ozercan I, Simsek M. Oxidant-antioxidant system changes relative to placental-umbilical pathology in patients with preeclampsia. Hypertens Pregnancy. 2005;24:147–57.CrossRefPubMed
37.
go back to reference Gupta S, Agarwal A, Sharma RK. The role of placental oxidative stress and lipid peroxidation in preeclampsia. Obs Gynecol Surv. 2005;60:807–16.CrossRef Gupta S, Agarwal A, Sharma RK. The role of placental oxidative stress and lipid peroxidation in preeclampsia. Obs Gynecol Surv. 2005;60:807–16.CrossRef
38.
go back to reference Mert I, Oruc AS, Yuksel S, Cakar ES, Buyukkagnici U, Karaer A, et al. Role of oxidative stress in preeclampsia and intrauterine growth restriction. J Obs Gynaecol Res. 2012;38:658–64.CrossRef Mert I, Oruc AS, Yuksel S, Cakar ES, Buyukkagnici U, Karaer A, et al. Role of oxidative stress in preeclampsia and intrauterine growth restriction. J Obs Gynaecol Res. 2012;38:658–64.CrossRef
39.
go back to reference Gaccioli F, White V, Capobianco E, Powell TL, Jawerbaum A, Jansson T. Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2alpha signaling and increases fetal growth in rats. Biol Reprod. 2013;89:96.CrossRefPubMed Gaccioli F, White V, Capobianco E, Powell TL, Jawerbaum A, Jansson T. Maternal overweight induced by a diet with high content of saturated fat activates placental mTOR and eIF2alpha signaling and increases fetal growth in rats. Biol Reprod. 2013;89:96.CrossRefPubMed
41.
go back to reference Roos S, Jansson N, Palmberg I, Saljo K, Powell TL, Jansson T. Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth. J Physiol. 2007;582(Pt 1):449–59.PubMedCentralCrossRefPubMed Roos S, Jansson N, Palmberg I, Saljo K, Powell TL, Jansson T. Mammalian target of rapamycin in the human placenta regulates leucine transport and is down-regulated in restricted fetal growth. J Physiol. 2007;582(Pt 1):449–59.PubMedCentralCrossRefPubMed
42.
go back to reference Rosario FJ, Kanai Y, Powell TL, Jansson T. Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells. J Physiol. 2013;591(Pt 3):609–25.PubMedCentralCrossRefPubMed Rosario FJ, Kanai Y, Powell TL, Jansson T. Mammalian target of rapamycin signalling modulates amino acid uptake by regulating transporter cell surface abundance in primary human trophoblast cells. J Physiol. 2013;591(Pt 3):609–25.PubMedCentralCrossRefPubMed
43.
go back to reference Roos S, Powell TL, Jansson T. Placental mTOR links maternal nutrient availability to fetal growth. Biochem Soc Trans. 2009;37(Pt 1):295–8.CrossRefPubMed Roos S, Powell TL, Jansson T. Placental mTOR links maternal nutrient availability to fetal growth. Biochem Soc Trans. 2009;37(Pt 1):295–8.CrossRefPubMed
44.
go back to reference Yano CL, Ventrucci G, Field WN, Tisdale MJ, Gomes-Marcondes MCC. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes. BMC Cancer. 2008;8:24.PubMedCentralCrossRefPubMed Yano CL, Ventrucci G, Field WN, Tisdale MJ, Gomes-Marcondes MCC. Metabolic and morphological alterations induced by proteolysis-inducing factor from Walker tumour-bearing rats in C2C12 myotubes. BMC Cancer. 2008;8:24.PubMedCentralCrossRefPubMed
45.
go back to reference Gazzaneo MC, Orellana RA, Suryawan A, Tuckow AP, Kimball SR, Wilson FA, et al. Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal. Pediatr Res. 2011;70:253–60.PubMedCentralCrossRefPubMed Gazzaneo MC, Orellana RA, Suryawan A, Tuckow AP, Kimball SR, Wilson FA, et al. Differential regulation of protein synthesis and mTOR signaling in skeletal muscle and visceral tissues of neonatal pigs after a meal. Pediatr Res. 2011;70:253–60.PubMedCentralCrossRefPubMed
46.
go back to reference Miyazaki M, McCarthy JJ, Fedele MJ, Esser KA. Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling. J Physiol. 2011;589(Pt 7):1831–46.PubMedCentralCrossRefPubMed Miyazaki M, McCarthy JJ, Fedele MJ, Esser KA. Early activation of mTORC1 signalling in response to mechanical overload is independent of phosphoinositide 3-kinase/Akt signalling. J Physiol. 2011;589(Pt 7):1831–46.PubMedCentralCrossRefPubMed
47.
go back to reference Suryawan A, Nguyen HV, Almonaci RD, Davis TA. Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated. Amino Acids. 2013;45:523–30.PubMedCentralCrossRefPubMed Suryawan A, Nguyen HV, Almonaci RD, Davis TA. Abundance of amino acid transporters involved in mTORC1 activation in skeletal muscle of neonatal pigs is developmentally regulated. Amino Acids. 2013;45:523–30.PubMedCentralCrossRefPubMed
48.
go back to reference Attaix D, Mosoni L, Dardevet D, Combaret L, Mirand PP, Grizard J. Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods. Int J Biochem Cell Biol. 2005;37:1962–73.CrossRefPubMed Attaix D, Mosoni L, Dardevet D, Combaret L, Mirand PP, Grizard J. Altered responses in skeletal muscle protein turnover during aging in anabolic and catabolic periods. Int J Biochem Cell Biol. 2005;37:1962–73.CrossRefPubMed
49.
go back to reference Boutry C, El-Kadi SW, Suryawan A, Wheatley SM, Orellana RA, Kimball SR, et al. Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs. Am J Physiol Endocrinol Metab. 2013;305:E620–31.PubMedCentralCrossRefPubMed Boutry C, El-Kadi SW, Suryawan A, Wheatley SM, Orellana RA, Kimball SR, et al. Leucine pulses enhance skeletal muscle protein synthesis during continuous feeding in neonatal pigs. Am J Physiol Endocrinol Metab. 2013;305:E620–31.PubMedCentralCrossRefPubMed
50.
go back to reference Wheatley SM, El-Kadi SW, Suryawan A, Boutry C, Orellana RA, Nguyen HV, et al. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate. Am J Physiol Endocrinol Metab. 2014;306:E91–9.PubMedCentralCrossRefPubMed Wheatley SM, El-Kadi SW, Suryawan A, Boutry C, Orellana RA, Nguyen HV, et al. Protein synthesis in skeletal muscle of neonatal pigs is enhanced by administration of beta-hydroxy-beta-methylbutyrate. Am J Physiol Endocrinol Metab. 2014;306:E91–9.PubMedCentralCrossRefPubMed
51.
go back to reference Gonçalves EM, Salomão EM, Gomes-Marcondes MC. Leucine modulates the effect of Walker factor, a proteolysis-inducing factor-like protein from Walker tumours, on gene expression and cellular activity in C2C12 myotubes. Cytokine. 2013;64:343–50.CrossRefPubMed Gonçalves EM, Salomão EM, Gomes-Marcondes MC. Leucine modulates the effect of Walker factor, a proteolysis-inducing factor-like protein from Walker tumours, on gene expression and cellular activity in C2C12 myotubes. Cytokine. 2013;64:343–50.CrossRefPubMed
Metadata
Title
Dietary leucine supplementation minimises tumour-induced damage in placental tissues of pregnant, tumour-bearing rats
Publication date
01-12-2016
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2103-x

Other articles of this Issue 1/2016

BMC Cancer 1/2016 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine