Roundup: HICCC at AACR 2023
HICCC Research Presented at Annual AACR Meeting
Thousands of researchers, clinicians, patients, and health advocates attended the AACR Annual Meeting this past week, held April 14 to 19 in Orlando, FL. With over 50,000 members, the AACR is one of the largest professional organizations dedicated to cancer research in the world, and their annual meeting is one of the largest in the country for the cancer research community. Dozens of HICCC members attended and presented their innovative research at this year’s meeting and were recognized for their significant scientific contributions in the field of cancer research.
HICCC Members Receive Scientific Achievement Awards
Two HICCC members, Cory Abate-Shen, PhD, and Riccardo Dalla-Favera, MD, received prestigious Scientific Achievement Awards from the AACR in recognition of their impactful careers in the field of cancer research. Dr. Abate-Shen was awarded the Women in Cancer Research Charlotte Friend Lectureship for her pioneering work in identifying novel mechanisms and advancing murine models in prostate and bladder cancer, as well as her leadership and mentorship for women cancer researchers. Dr. Dalla-Favera received the AACR’s Award for Outstanding Achievement in Blood Cancer Research in recognition of his over 40-year career working to advance scientific understanding of lymphoma and cancer genetics.
“Columbia University and the Herbert Irving Comprehensive Center are fortunate to have two members recognized for their outstanding scientific achievements,” says Anil K. Rustgi, MD, director of the Herbert Irving Comprehensive Cancer Center. “Annually, the AACR gives out multiple awards, and a very limited number of institutions have the honor of receiving two awards amongst their faculty.”
HICCC members presented their research in more than 50 different sessions, including three major symposia, seven minisymposia, and 30 posters. Topics ranged from novel biomarkers, clinical trials, therapies, disparities and outcomes, and more. Below are a few selected research highlights.
From the Patient Voice to the FDA, Early Phase Clinical Trials
“Incorporating patient reported outcomes in dose-finding clinical trials”
Shing M. Lee, PhD discussed considerations for incorporating patient reported outcomes in dose finding clinical trials and introduce methods that allow for the inclusion of patient reported outcomes to estimate the optimal dose for cancer treatments. Dr. Lee's research interest is in the implementation of novel designs for early-stage clinical trials, particularly in the development of novel statistical methods for dose optimization of targeted and immunotherapy cancer agents and methods for summarizing and visualizing adverse events that better reflect the toxicity burden of patients.
Disparities and Cancer Outcomes
“Measures of pre-diagnostic allostatic load and breast cancer outcomes in Black women”
Adana A.M. Llanos, PhD, MPH highlighted findings from the Women’s Circle of Health Study that show a significant association between pre-diagnostic measures of allostatic load – a marker of cumulative physiologic stress – with unfavorable breast tumor features and poorer quality of life 24 months post-diagnosis, specifically in Black women. A major focus of Dr. Llanos' research is to examine risk factors that contribute to increased breast cancer incidence at younger ages, increased incidence of more aggressive tumors, and increased mortality among Black women.
Cancer Ecosystem: Malignant Cells, Microenvironment and More
Metastasis to the brain occurs frequently with advanced cancers and is associated with poor response to existing therapies and poor prognosis, but the underlying biology is poorly understood.
Benjamin Izar, MD, chaired the session and discussed new research using cutting-edge technologies to directly study the genetic and phenotypic features of human brain metastases (melanoma and non-small cell lung cancer), identifying a novel strategy that may more effectively treat patients with brain metastasis. Dr. Izar’s research aims to elucidate interactions of cancer and immunity in the tumor development, metastasis and drug resistance using high-dimensional functional single-cell genomics and imaging to inform better selection and development of therapies.
Clinical Trials Plenary Session: Novel Biomarker-driven Molecularly Targeted Therapy Trials
This clinical trial plenary session included results of a clinical trial, co-authored by Benjamin Herzberg, MD, exploring safety and effectiveness of a new combination therapy. In this trial, a PARP inhibitor – which has been known to work well in patients with BRCA mutations, which are usually breast, prostate, and ovarian cancers – was combined with a novel drug, called an ATR inhibitor, or camonsertib. ATR inhibitors have shown some clinical promise, but have been difficult to develop and their efficacy as a standalone therapy has been limited. The trial found that the overall activity of the combination was promising, with lots of responses in various tumor types and especially ovarian tumors. The most troublesome side effect was anemia, which led to dose reductions in nearly all patients. Dr. Herzberg is opening a clinical trial to address potential mitigation of this toxicity.
Highlights From Our Trainees
Minisymposium: Late-breaking Research
Li-Fraumeni syndrome-associated dimer-forming mutant p53 promotes transactivation-independent mitochondrial cell death
Joshua Choe, PhD student (from the lab of Carol Prives, PhD) presented new findings about the characteristics of tumor suppressor p53 (TP53), a protein that plays a critical role in preventing cancer. TP53 is the most commonly mutated gene in cancer and occurs in more than 50% of all cancers. These new findings could have clinical implications for patients with this mutation. A leading light in basic cancer research, Dr. Prives has transformed the field by immersing herself in characterizing the structure and function of the p53 tumor suppressor and its binding partners, notably Mdm2.
Mini-Symposium: Cutting-edge Computational Approaches for Precision Oncology and Cancer Biology
“Identifying neuroendocrine prostate cancer drivers using in vivo forward genetics”
In this mini-symposium, Alessandro Vasciaveo, PhD (from the lab of Andrea Califano, Dr) presented research investigating the emergence of Neuroendocrine Prostate Cancer (NEPC), a lethal variant that frequently arises in the clinic from castration resistant prostate cancer (CRPC) following second-generation anti-androgen therapy. The investigators performed a forward genetic screening on genetically-engineered mouse models (GEMMs) of CRPC and found that many tumors developed features of NEPC. The investigators then performed an integrative analysis using several computational algorithms to identify a histone deacetylase enzyme as an upstream modulator of NEPC activity and a potential therapeutic target for treating this aggressive form of prostate cancer.
Each year, the AACR Annual Meeting Scholar-in-Training Award program provides grants to young investigators with support from 68 cancer research foundations, corporations, individuals, and other organizations dedicated to the fight against cancer.
Scholar-in-Training Awards are highly competitive and recognize exceptional young investigators presenting exemplary papers at the AACR Annual Meeting. This year, the HICCC was proud to have ten of its promising young investigators receive travel awards.
Carla Bertulfo, MPhil
"Therapeutic Targeting of NOTCH1 and Neddylation Pathway in T-Cell Acute Lymphoblastic Leukemia"
Jana Biermann, PhD
"Multi-modal Single-Cell Analysis of Immunotherapy-Experienced Cutaneous and Mucosal Melanoma"
Lindsay A. Caprio, BS
"Relief of Chromosomal Instability-Induced cGAS-STING Signaling Sensitizes STK11-Mutant Non-Small Cell Lung Cancer to Immune Checkpoint Blockade"
Alvaro Curiel Garcia, PhD
"BMAL2 is a KRAS-Dependent Master Regulator of Hypoxic Response in Pancreatic Ductal Adenocarcinoma"
Lucas Zhongming Hu, PhD
"Systems Pharmacology Approaches to Study Tumor Drug mechanism of Action"
Sungsoo Kim, PhD
"Kinetics of RTK Activation Determine ERK Signaling Dynamics and Resistance to BRAF and MEK Inhibitors"
Guodong Lian, MD, PhD
"Mutation Biases SCJ Progenitor Cells Towards Dysplasia Rather than Metaplasia in Barrett's Esophagus"
Somnath Tagore, PhD
"Multi-Modal Single-Cell and Spatial Genomics Reveals Genomic, Adaptive and Microenvironmental Features of Human Nonsmall Cell Lung Cancer Brain Metastasis"
Alessandro Vasciaveo, PhD
"Identifying neuroendocrine prostate cancer drivers using in vivo forward genetics"
Xiaofei Zhi, MD, PhD
"Sensory Innervation Directly Promotes Gastric Cancer and Modulates the Tumor Microenvironment"