Michael P DiGiovanna, MD, PhD

Research Interests

Breast Neoplasms; Medical Oncology; Pharmacology; Protein-Tyrosine Kinases; Signal Transduction; Clinical Trial

Research Organizations

Medical Oncology: Subset Medical Oncology Faculty

Faculty Research

WHRY Pilot Project Program Investigators

Yale Cancer Center: Signal Transduction

Office of Cooperative Research

Research Summary

We study signal transduction by growth factor receptor tyrosine kinases, focusing on the EGFR/HER2/ErbB family, including the impact of signaling by these receptors on clinical outcomes and response to targeted therapies for cancer, and their potential as therapeutic targets in novel combination therapies. A major focus in our laboratory has been the interaction of HER2 signaling with estrogen receptor (ER) signaling in breast cancer, and more recently with IGF-I receptor signaling, and the effects of inhibitors of these receptors in combination targeted therapies. We have also found that in breast cancer patients, tumors harboring activated HER2 have adverse prognosis, and these tumors have co-overexpression of EGFR. We continue to study how signaling by these receptors impacts responses to different types of therapies and explore targeting these receptors in combination with other novel targeted therapeutics.

Specialized Terms: Breast cancer; HER-2/neu/ErbB-2; IGF1 receptor; EGF receptor; Growth factor receptor tyrosine protein kinases in malignancy; Estrogen receptor; Signal transduction; Breast cancer clinical trials

Extensive Research Description

We study signal transduction by growth factor receptor tyrosine kinases, focusing on the EGFR/HER2/ErbB family, including the impact of signaling by these receptors on clinical outcomes and response to targeted therapies for cancer, and their potential as therapeutic targets in novel combination therapies. A major focus in our laboratory has been the interaction of HER2 signaling with estrogen receptor (ER) signaling in breast cancer, and more recently with IGF-I receptor signaling, and the effects of inhibitors of these receptors in combination targeted therapies. We have also found that in breast cancer patients, tumors harboring activated HER2 have adverse prognosis, and these tumors have co-overexpression of EGFR. We continue to study how signaling by these receptors impacts responses to different types of therapies and explore targeting these receptors in combination with other novel targeted therapeutics.Therapeutic implications of interactions of IGF-I receptor with HER2 and estrogen receptor

Full List of PubMed Publications

• Foldi J, Mougalian S, Silber A, Lannin D, Killelea B, Chagpar A, Horowitz N, Frederick C, Rispoli L, Burrello T, Abu-Khalaf M, Sabbath K, Sanft T, Brandt DS, Hofstatter EW, Hatzis C, DiGiovanna MP, Pusztai L: Single-arm, neoadjuvant, phase II trial of pertuzumab and trastuzumab administered concomitantly with weekly paclitaxel followed by 5-fluoruracil, epirubicin, and cyclophosphamide (FEC) for stage I-III HER2-positive breast cancer. Breast Cancer Res Treat. 2018 Feb 2; 2018 Feb 2. PMID: 29396664
• Chagpar AB, Horowitz N, Sanft T, Wilson LD, Silber A, Killelea B, Moran MS, DiGiovanna MP, Hofstatter E, Chung G, Pusztai L, Lannin DR: Discussion of: "Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer?" Am J Surg. 2017 Dec; 2017 Sep 30. PMID: 28987415
• Chagpar AB, Horowitz N, Sanft T, Wilson LD, Silber A, Killelea B, Moran MS, DiGiovanna MP, Hofstatter E, Chung G, Pusztai L, Lannin DR: Does lymph node status influence adjuvant therapy decision-making in women 70 years of age or older with clinically node negative hormone receptor positive breast cancer? Am J Surg. 2017 Dec; 2017 Sep 18. PMID: 28939252
• Dzimitrowicz H, Mougalian S, Storms S, Hurd S, Chagpar AB, Killelea BK, Horowitz NR, Lannin DR, Harigopal M, Hofstatter E, DiGiovanna MP, Adelson KB, Silber A, Abu-Khalaf M, Chung G, Zaheer W, Abdelghany O, Hatzis C, Pusztai L, Sanft TB: Impacts of Early Guideline-Directed 21-Gene Recurrence Score Testing on Adjuvant Therapy Decision Making. J Oncol Pract. 2017 Dec; 2017 Oct 19. PMID: 29048991
• Chagpar AB, Hatzis C, Pusztai L, DiGiovanna MP, Moran M, Mougalian S, Sanft T, Evans S, Hofstatter E, Wilson LD, Lannin DR: Association of LN Evaluation with Survival in Women Aged 70 Years or Older With Clinically Node-Negative Hormone Receptor Positive Breast Cancer. Ann Surg Oncol. 2017 Oct; 2017 Aug 1. PMID: 28766195
• Chakraborty A, Hatzis C, DiGiovanna MP: Co-targeting the HER and IGF/insulin receptor axis in breast cancer, with triple targeting with endocrine therapy for hormone-sensitive disease. Breast Cancer Res Treat. 2017 May; 2017 Feb 24. PMID: 28236033
• Yushak ML, Han G, Bouberhan S, Epstein L, DiGiovanna MP, Mougalian SS, Sanft TB, Abu-Khalaf MM, Chung GG, Stein SM, Goldberg SB, Pusztai L, Hofstatter EW: Patient preferences regarding incidental genomic findings discovered during tumor profiling. Cancer. 2016 May 15; 2016 Mar 11. PMID: 26970385
• Chakraborty AK, Zerillo C, DiGiovanna MP: In vitro and in vivo studies of the combination of IGF1R inhibitor figitumumab (CP-751,871) with HER2 inhibitors trastuzumab and neratinib. Breast Cancer Res Treat. 2015 Aug; 2015 Jul 21. PMID: 26195122
• Mougalian SS, Soulos PR, Killelea BK, Lannin DR, Abu-Khalaf MM, DiGiovanna MP, Sanft TB, Pusztai L, Gross CP, Chagpar AB: Use of neoadjuvant chemotherapy for patients with stage I to III breast cancer in the United States. Cancer. 2015 Aug 1; 2015 Apr 22. PMID: 25902916
• Abu-Khalaf MM, Baumgart MA, Gettinger SN, Doddamane I, Tuck DP, Hou S, Chen N, Sullivan C, Lezon-Geyda K, Zelterman D, Hatzis C, Deshpande H, Digiovanna MP, Azodi M, Schwartz PE, Harris LN: Phase 1b study of the mammalian target of rapamycin inhibitor sirolimus in combination with nanoparticle albumin-bound paclitaxel in patients with advanced solid tumors. Cancer. 2015 Jun 1; 2015 Feb 3. PMID: 25649370
• Chakraborty AK, Mehra R, Digiovanna MP: Co-targeting ER and HER family receptors induces apoptosis in HER2-normal or overexpressing breast cancer models. Anticancer Res. 2015 Mar. PMID: 25750271
• Acevedo-Gadea C, Hatzis C, Chung G, Fishbach N, Lezon-Geyda K, Zelterman D, DiGiovanna MP, Harris L, Abu-Khalaf MM: Sirolimus and trastuzumab combination therapy for HER2-positive metastatic breast cancer after progression on prior trastuzumab therapy. Breast Cancer Res Treat. 2015 Feb; 2015 Feb 17. PMID: 25687356
• Fenn KM, Evans SB, McCorkle R, DiGiovanna MP, Pusztai L, Sanft T, Hofstatter EW, Killelea BK, Knobf MT, Lannin DR, Abu-Khalaf M, Horowitz NR, Chagpar AB: Impact of financial burden of cancer on survivors' quality of life. J Oncol Pract. 2014 Sep; 2014 May 27. PMID: 24865220
• Brown JR, DiGiovanna MP, Killelea B, Lannin DR, Rimm DL: Quantitative assessment Ki-67 score for prediction of response to neoadjuvant chemotherapy in breast cancer. Lab Invest. 2014 Jan; 2013 Nov 4. PMID: 24189270
• Schulman-Green D, Bradley EH, Knobf MT, Prigerson H, DiGiovanna MP, McCorkle R: Self-management and transitions in women with advanced breast cancer. J Pain Symptom Manage. 2011 Oct; 2011 Mar 27. PMID: 21444183
• Chakraborty AK, Welsh A, Digiovanna MP: Co-targeting the insulin-like growth factor I receptor enhances growth-inhibitory and pro-apoptotic effects of anti-estrogens in human breast cancer cell lines. Breast Cancer Res Treat. 2010 Apr; 2009 Apr 1. PMID: 19337828
• Koay DC, Zerillo C, Narayan M, Harris LN, DiGiovanna MP: Anti-tumor effects of retinoids combined with trastuzumab or tamoxifen in breast cancer cells: induction of apoptosis by retinoid/trastuzumab combinations. Breast Cancer Res. 2010; 2010 Aug 9. PMID: 20696059
• Christy CJ, Thorsteinsson D, Grube BJ, Black D, Abu-Khalaf M, Chung GG, DiGiovanna MP, Miller K, Higgins SA, Weidhaas J, Harris L, Tavassoli FA, Lannin DR: Preoperative chemotherapy decreases the need for re-excision of breast cancers between 2 and 4 cm diameter. Ann Surg Oncol. 2009 Mar; 2009 Jan 9. PMID: 19132447
• Nishihori T, Choi J, DiGiovanna MP, Thomson JG, Kohler PC, McGurn J, Chung GG: Carpal tunnel syndrome associated with the use of aromatase inhibitors in breast cancer. Clin Breast Cancer. 2008 Aug. PMID: 18757265
• Grube BJ, Christy CJ, Black D, Martel M, Harris L, Weidhaas J, Digiovanna MP, Chung G, Abu-Khalaf MM, Miller KD, Higgins SA, Philpotts L, Tavassoli FA, Lannin DR: Breast sentinel lymph node dissection before preoperative chemotherapy. Arch Surg. 2008 Jul. PMID: 18645113
• DiGiovanna MP, Stern DF, Edgerton S, Broadwater G, Dressler LG, Budman DR, Henderson IC, Norton L, Liu ET, Muss HB, Berry DA, Hayes DF, Thor AD: Influence of activation state of ErbB-2 (HER-2) on response to adjuvant cyclophosphamide, doxorubicin, and fluorouracil for stage II, node-positive breast cancer: study 8541 from the Cancer and Leukemia Group B. J Clin Oncol. 2008 May 10; 2008 Apr 7. PMID: 18390970
• Chakraborty AK, Liang K, DiGiovanna MP: Co-targeting insulin-like growth factor I receptor and HER2: dramatic effects of HER2 inhibitors on nonoverexpressing breast cancer. Cancer Res. 2008 Mar 1. PMID: 18316619
• Abu-Khalaf MM, Juneja V, Chung GG, DiGiovanna MP, Sipples R, McGurk M, Zelterman D, Haffty B, Reiss M, Wackers FJ, Lee FA, Burtness BA: Long-term assessment of cardiac function after dose-dense and -intense sequential doxorubicin (A), paclitaxel (T), and cyclophosphamide (C) as adjuvant therapy for high risk breast cancer. Breast Cancer Res Treat. 2007 Sep; 2006 Oct 19. PMID: 17051423
• Wang CX, Koay DC, Edwards A, Lu Z, Mor G, Ocal IT, Digiovanna MP: In vitro and in vivo effects of combination of Trastuzumab (Herceptin) and Tamoxifen in breast cancer. Breast Cancer Res Treat. 2005 Aug. PMID: 16155796
• DiGiovanna MP, Stern DF, Edgerton SM, Whalen SG, Moore D 2nd, Thor AD: Relationship of epidermal growth factor receptor expression to ErbB-2 signaling activity and prognosis in breast cancer patients. J Clin Oncol. 2005 Feb 20. PMID: 15718311
• Argiris A, Wang CX, Whalen SG, DiGiovanna MP: Synergistic interactions between tamoxifen and trastuzumab (Herceptin). Clin Cancer Res. 2004 Feb 15. PMID: 14977844
• DiGiovanna MP, Chu P, Davison TL, Howe CL, Carter D, Claus EB, Stern DF: Active signaling by HER-2/neu in a subpopulation of HER-2/neu-overexpressing ductal carcinoma in situ: clinicopathological correlates. Cancer Res. 2002 Nov 15. PMID: 12438265
• Digiovanna MP, Stern DF, Roussel RR: Production of antibodies that recognize specific tyrosine-phosphorylated peptides. Curr Protoc Immunol. 2002 Nov. PMID: 18432869
• Khan AJ, King BL, Smith BD, Smith GL, DiGiovanna MP, Carter D, Haffty BG: Characterization of the HER-2/neu oncogene by immunohistochemical and fluorescence in situ hybridization analysis in oral and oropharyngeal squamous cell carcinoma. Clin Cancer Res. 2002 Feb. PMID: 11839675
• DiGiovanna MP, Roussel RR, Stern DF: Production of antibodies that recognize specific tyrosine-phosphorylated peptides. Curr Protoc Cell Biol. 2002 Feb. PMID: 18228399

Edit this profile