Numerous studies have indicated that pain is the top ranked symptom in head and neck cancer (HNC)patients. However, available treatments are limited and associated with severe side effects addingsubstantially to the burden of having cancer. Thus, there is a critical need for novel analgesics.

The majority of breast cancer cases are estrogen receptor (ER?)-positive. While hormonal therapyimproves clinical outcomes for about half of patients with ER?-positive breast cancer, de novo or acquiredresistance represents a significant clinical challenge. Among several underlying mechanisms, hot-spot pointmutants of ER? are known to confer therapeutic resistance due to their estrogen-independent transcriptionalactivity. Thus, mitigating aberrant transcription activity of these ER? mutants holds promise for overcomingtherapeutic resistance in treatment of ER?-positive breast cancer.

The mTORC1 pathway regulates multiple cellular processes to promote a switch from catabolic toanabolic metabolism and is thus under tight regulatory control by growth factor signaling and nutrientsensing pathways. Dysregulation of this complex machinery is implicated in many cancers, so definingthe key mechanisms by which mTORC1 senses changes in cellular homeostasis to activate growthsignals is of great relevance. Spatial regulation of mTORC1 signaling has been recognized as a majormechanism that influences the cellular response to nutrients and the lysosome is central to thisprocess.

Uterine leiomyomas (LM; fibroids) are monoclonal neoplasms of the myometrium (MM) and represent themost frequent tumors in women worldwide. Although benign, they nonetheless account for significantgynecologic and reproductive dysfunction.

The tumor suppressor BRCA1 plays an important role in the homologous recombination (HR) pathwayof DNA double strand break (DSB) repair. From a mechanistic perspective, BRCA1 facilitates recruitment ofnucleases required for end resection, the commitment step in HR repair, yet paradoxically, BRCA1 has beenshown to inhibit the nuclease activity in vitro. It is unclear how nuclease-recruiting and -inhibiting activities ofBRCA1 can be reconciled in HR repair.

Most BRCA1-asociated breast tumors are basal-like, yet they originate from luminal progenitor cells.BRCA1 plays important roles in double strand break (DSB) repair and response to DNA replication stress.However, it remains a conundrum as to whether these ubiquitously important functions of BRCA1 are sufficientto account for its cell lineage-specific breast tumor suppression. Filling this longstanding intellectual disconnectcould inform more effective risk assessment and disease prevention.