Annual Meeting

AM 2014 Daily News Sunday C

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In the Eye of the Storm: Cancer Care in the Philippines Roselle De Guzman, MD O n November 8, 2013, millions of people across the globe stared at their television sets, horrifi ed by the devastation caused by typhoon Haiyan (locally known as Yolanda) in central Philippines. It was the 24th typhoon to enter the Philip- pine Area of Responsibility last year. With a force equivalent to a category 5 hurricane, it was one of the strongest to strike land on record. Typhoon Haiyan directly swept through six provinces in the Visayas region: East- ern Samar, Leyte, Iloilo, Palawan, and Daanbantayan and Bantayan Island, both in Cebu (Fig. 1). The areas struck by the typhoon were some of the poorest parts of the Philippines. All homes, buildings, roads, and other physical infrastructures in the path of the storm were profoundly damaged or destroyed. A two-story-high storm surge accompanied by monstrous winds, smashed the city of Tacloban, the capital and seat of government of Eastern Visayas region. Tacloban was the most badly hit—most of its communities were washed away. Haiyan is the deadliest Philippine typhoon on record. The leading causes of The B-Cell Receptor Pathway: A Critical Component of Healthy and Malignant Immune Biology Jason A. Dubovsky, PhD A more detailed version of this article is available on ASCO Daily News Online, including insights into ibrutinib's ability to inhibit IL-2 inducible T-cell kinase (ITK) and explanations as to why the development of enzastaurin was halted in phase III. Additional fi gures and a full reference list also are available online. T he B-cell receptor (BCR) pathway has recently become a prime tar- get for the treatment of many incurable B-cell malignancies including mantle cell lymphoma (MCL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and chronic lymphocytic leukemia (CLL). 1 Our over- all molecular understanding of the com- plex BCR pathway is quite mature given decades of study regarding its role in healthy immune function, B-lympho- cyte development, and the initiation of humoral immunity. The fact that many B-cell malignancies rely on chronic stimulation via the BCR pathway, how- ever, has only recently been appreciated. The litany of BCR-targeted therapies in clinical or pre- clinical devel- opment, along with the real- ization that in- tact lymphoid pathways are commandeered in the neoplastic setting, makes understand- ing the molecular basis of this lynchpin pathway especially important. Biologic Imperatives in B-Lymphocytes Despite the recent fervor regarding BCR-targeted therapies, a comprehen- sive understanding of the pathway itself resides in an appreciation of its use in healthy immune function. In its sim- plest form, the BCR and associated path- ways elicit three basic functions intrinsic to B-cell biology including: ■ providing activation signaling in the absence of specifi c target ligands to establish a long-lived and diverse pool of functional healthy B cells capable of rapidly responding to external pathogens by recognition of their individual cognate antigenic ligand, ■ driving the development of antigen- presenting cell functions in mature B- lymphocytes and presenting peptides derived from the cognate antigen on the surface to helper CD4 T-cells in the context of major histocompati- bility class II (MHC-II), and ■ eliciting the development and production of high-affi nity soluble immunoglobulins of an isotype uniquely capable of effectively rec- ognizing and binding the cognate antigenic target. The molecular collaboration required to effectively orchestrate these tasks is deceptively complex. Ultimately, lym- phocytes, including malignant and healthy B cells, rely on three transcrip- tion factors to varying degrees. These include nuclear factor of activated T- cells (NFAT), nuclear factor-kappa B (NF-kappaB), and activator protein 1 (AP-1), each of which drives multiple prosurvival and proliferative effects downstream of the BCR. A fourth ele- ment of BCR pathway activation is cyto- skeletal reorganization, which is essen- tial to transduce and amplify the signals from the BCR, as well as to execute widespread cellular functions. The pri- mary imperative of BCR signaling path- ways is to properly stimulate these three signaling pathways in conjunction with See Cancer Care in the Philippines, Page 4C See B-Cell Receptor Pathway, Page 10C INSIDE SUNDAY SECTION C Patient Turned Advocate, Michael S. Katz, Presented with Partners in Progress Award 5C Top 10 Highlights of the 2014 Genitourinary Cancers Symposium 14C Expert Editorial: The Oncologist's Role in Tobacco Cessation 18C ASCO Honors 50th Anniversary of Surgeon General's Report 18C Dr. Kornelia Polyak's Quest to Advance Understanding of Ductal Carcinoma In Situ of the Breast 19C Dr. Lidia Schapira Named JCO Art of Oncology Editor 19C ASCO L DP Participant Dr. Quyen Chu Appointed by President Obama to Key Administration Post 23C Expert Editorial: Single-Component QOPI ® Certifi cation within a Large Practice 25C Exhibitor Listings 28C Meeting Supporters 29C Diversity in Oncology Initiative 37C ASCO Affi liate Health Member Peg Ford: A Journey from Patient to Patient Advocate 38C ASCO-Sponsored Patient Advocacy Booth, Programs, Resources 38C DAILY NEWS SUNDAY · J U N E 1 , 20 1 4 C SECTION Dr. Jason A. Dubovsky CANCER CARE IN THE PHILIPPINES 3 5 4 3 2 1 PACIFIC OCEAN SOUTH CHINA SEA SULU SEA PHILIPPINE SEA CHINA INDONESIA BURMA THAILAND LAOS VIETNAM PHILIPPINES CAMBODIA BRUNEI MALYASIA SINGAPORE Manila Puerto Princesa Davao City Leyte Samar Panay Hue Quang Ngai Quy Nhon Hanoi N Fig. 1. The Path Taken by Typhoon Haiyan E X P E R T E D I T O R I A L The litany of BCR- targeted therapies in clinical or preclinical development, along with the realization that intact lymphoid pathways are commandeered in the neoplastic setting, makes understanding the molecular basis of this lynchpin pathway especially important. —DR. JASON A. DUBOVSKY

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