Miami Cancer Institute: Hematology Oncology Grand Rounds – Overcoming Resistance to Targeted Therapies in AML: IDH as a Therapeutic Paradigm
Precision oncology is the practice of matching one therapy to one specific patient, based on particular genetic tumor alterations, in order to achieve the best clinical response. Despite an expanding arsenal of targeted therapies, many patients still have a poor outcome because tumor cells show a remarkable capacity to develop drug resistance, thereby leading to tumor relapse. Besides genotype-driven resistance mechanisms, tumor microenvironment (TME) peculiarities strongly contribute to generate an intratumoral phenotypic heterogeneity that affects disease progression and treatment outcome. In this review, we describe how TME-mediated metabolic heterogeneities actively participate in therapeutic failure. We report how a lactate-based metabolic symbiosis acts as a mechanism of adaptive resistance to targeted therapies and we describe the role of mitochondrial metabolism, in particular oxidative phosphorylation (OXPHOS), to support the growth and survival of therapy-resistant tumor cells in a variety of cancers. Finally, we detail potential metabolism-interfering therapeutic strategies aiming to eradicate OXPHOS-dependent, relapse-sustaining malignant cells, and we discuss relevant (pre)clinical models that may help integrate TME-driven metabolic heterogeneity in precision oncology.
Target Audience
This educational program is directed toward hematologists, oncologists, pathologists, radiation oncologists, palliative care staff, hematology oncology nurses, pharmacists and other allied health care team members interested in the treatment of patients with hematologic malignancies.
NOTE: Due to limited space, this conference is open to Baptist Health affiliated Medical Staff and Clinical Employees.
Learning Objectives
- Summarize the landscape of mutations that predict therapeutic response and non-response to recently approved targeted therapies for AML.
- Identify strategies to overcome resistance to targeted therapies in patients with AML.
Eytan M. Stein
Assistant Attending Physician
Director, Program for Drug Development in Leukemia
Leukemia Service
Department of Medicine
Memorial Sloan Kettering Cancer Center
New York, New York
Eytan M. Stein, M.D., indicated that he has received grant/research support from Daiichi, Astellas, Celgene, Agios, Syros, Bioline, Pfizer, Abbvie, Genentech, Seattle Genetics and Amgen. Dr. Stein is also a shareholder of Auron Therapeutics. He will not include off-label or unapproved product usage in his presentation or discussion.
Non-faculty contributors and others involved in the planning, development, and editing/review of the content have relevant financial relationships to disclose.
Baptist Health South Florida is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians. Baptist Health has been re-surveyed by the ACCME and awarded Commendation for 6 years as a provider of CME for physicians.
Baptist Health South Florida designates this live activity for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
This activity has been approved for 1 credit hour, CE Broker Course #20-737016, by the Florida Boards of Medicine and Osteopathic Medicine and by the Florida Council of Physician Assistants.
This activity has also been approved for 1 credit hour for Nurse Practitioners, Nurses, Pharmacists, Occupational Therapists and Respiratory Therapists (personal growth). Baptist Health South Florida CE Broker Provider #50-182.
Available Credit
- 1.00 AMA PRA Category 1 Credit™
- 1.00 General certificate of attendance
- 1.00 Nurse Practitioners
- 1.00 Florida Board of Nursing
- 1.00 Florida Board of Occupational Therapy
- 1.00 Florida Board of Pharmacy
- 1.00 Florida Board of Respiratory Therapy
NOTE: Due to limited space, this conference is open to Baptist Health affiliated Medical Staff and Clinical Employees.
Required Hardware/Software
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