Tipifarnib, a Potential Adjuvant That Unlocks Therapeutic Resistance by Normalizing Microenvironment

Lin Tian^1* & Sicong Zhang²

¹Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA
²Laboratory of Biochemistry and Molecular Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA

Lin Tian, Cancer Biology and Genetics Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA.

Keywords: Microenvironment; Myofibroblast; Mutations; Monotherapy

Abstract

More than 1.5 million new cancer cases are diagnosed in US every year [1]. Unlike the normal cells that cooperate with each other to form an ecosystem within the tissue, the cancer cells break the rules by bypassing the normal proliferation, breaching the basement membrane, disseminating into circulation and finally establishing distant colonization [2]. To initiate this malignant cellular program, cancer cells hijack a variety of existing cellular mechanisms that are critical to normal tissue development and regeneration [3]. Despite the increasing knowledge on these molecular regulators leveraged by cancer cells to fulfill the aberrancy, most advanced cancers are still incurable, indicating the therapies to treat cancer have not kept up. In fact, the majority of current therapeutic regimens are designed to target cancer cells. However, the neighbors of cancer cells – especially the connective tissue or stroma – are far from passive bystanders [4].

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