Abstract 5122: A novel topical candidate for chemotherapy and radiotherapy-induced alopecia (CRIA) through local modulation of apoptosis

Abstract

Abstract Chemotherapy- or radiotherapy-induced alopecia (CRIA) is a common side effect of adjuvant and metastatic chemotherapy regimens or radiotherapy treatments. The likelihood of alopecia depends on the types and modes of treatment modalities. In cancer patients undergoing chemotherapy, the hair loss incidence is estimated to be 65%. Although CRIA is often assumed to be an unavoidable and transient side effect that can be dealt with using wigs, it is considered by the sufferers the most visible and emotionally distressing consequence of cancer therapies, giving negative repercussions on various aspects of quality of life (QOL). There are no approved pharmacologic treatments available for CRIA, and the outcome from scalp cooling devices are of variable quality. Normal hair cycle mainly consists of growth phase (anagen), regression phase (catagen), shedding phase (telogen) and resting phase (telogen). In the course of CRIA, the rapidly growing and dividing cell populations in anagen phase are damaged by the systemic chemotoxic agents and undergo unwanted premature apoptosis, consequently inducing premature onset of catagen. Apoptosis is finely tuned by endogenous and exogenous factors. The extrinsic pathway is principally mediated by an apoptosis stimulus factor, Fas. The intrinsic pathway is essentially mitochondria dependent and executed by members of Bcl-2 (B cell lymphoma-2). Bcl-2 level is depressed in the scalp of balding subjects, indicating a key role of apoptosis. A previous study using mouse model revealed that certain chemo-agent (e.g. cyclophosphamide) caused up-regulation of the pro-apoptotic protein p53 in root sheaths and hair matrix, sensitizing hair follicular cells to apoptosis. In contrast, p53-deficient mice showed neither hair loss nor abnormal apoptosis in hair matrix keratinocytes, most likely as a result of down-regulation of Fas and increased expression of the anti-apoptotic protein Bcl-2. As Bcl-2 level in non-alopecia subjects has not been documented so far, we conducted a scalp biopsy study in order to measure the “normal” Bcl-2 level in non-alopecia subjects. We then compared the “normal” Bcl-2 level in non-alopecia subjects with the level of Bcl-2 in androgenetic alopecia (AGA) volunteers, before and after topical application of a GMP-grade botanical extract (“the Product”). It turned out that, after Product application, the level of scalp Bcl-2 was restored, towards normal level, consequently preventing early onset of the apoptosis-driven catagen phase. Pharmacological inhibition of apoptosis pathways has been proposed to prevent chemotherapy induced alopecia. The outcome obtained from our studies have now made it possible to study the potential benefit from positive modulation of hair follicular cell apoptotic process in cancer patients suffering from unwanted hair loss due to chemo- or radiotherapy. Citation Format: Jiawei Liu, Saad Harti. A novel topical candidate for chemotherapy and radiotherapy-induced alopecia (CRIA) through local modulation of apoptosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5122. doi:10.1158/1538-7445.AM2014-5122