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Title: | Technological and therapeutic advances in advanced small cell lung cancer. | Authors: | Alamgeer M. ;Lum C. | Institution: | (Lum, Alamgeer) Department of Medical Oncology, Monash Health and Monash University, Clayton, VIC 3168, Australia (Alamgeer) Centre for Cancer Research, Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia | Issue Date: | 1-Nov-2019 | Copyright year: | 2019 | Publisher: | MDPI AG (Postfach, Basel CH-4005, Switzerland. E-mail: indexing@mdpi.com) | Place of publication: | Switzerland | Publication information: | Cancers. 11 (10) (no pagination), 2019. Article Number: 1570. Date of Publication: October 2019. | Journal: | Cancers | Abstract: | Small cell lung cancer (SCLC) accounts for approximately 10-15% of all lung cancers. The prognosis is poor with median survival in the advanced stage remaining at around 12 months. Despite applying every known therapeutic approach, no major breakthrough has improved the overall survival in the last 30 years. Historically, experiments performed on conventional cell lines may have limitations of not accurately reflecting the complex biological and genomic heterogeneity of this disease. However, additional knowledge gained from recently developed genetically engineered mouse models (GEMMs) and patient derived xenografts (PDXs) have made encouraging inroads. Whole genome sequencing (WGS) data reveals a high mutational burden and a number of genetic alterations but low frequency of targetable mutations. Despite several failures, considerable therapeutic opportunities have recently emerged. Potentially promising therapies include those targeting DNA damage repair, stem cell/renewal and drug resistant mechanisms. Modest success has also been achieved with immune checkpoint inhibitors while therapeutic exploration of various other components of the immune system is underway. However, the complex heterogeneities reflect the need for accurate bio-markers to translate novel discoveries into clinical benefit. Additionally, the molecular mechanisms that differentiate chemo-sensitive from chemo-refractory disease remain unknown. Obtaining reliable tumour samples by utilising novel techniques such as endobronchial ultrasound guided needle aspiration or adopting to liquid biopsies are becoming popular. This review will focus on recent technological and therapeutic advancements to surmount this recalcitrant disease.Copyright © 2019 by the authors. Licensee MDPI, Basel, Switzerland. | DOI: | http://monash.idm.oclc.org/login?url=http://dx.doi.org/10.3390/cancers11101570 | ISSN: | 2072-6694 (electronic) | URI: | https://repository.monashhealth.org/monashhealthjspui/handle/1/35889 | Type: | Review | Subjects: | drug efficacy drug potentiation encephalitis/si [Side Effect] fatigue/si [Side Effect] genetic heterogeneity genomics hand foot syndrome/si [Side Effect] hedgehog signaling human hypertension/si [Side Effect] liquid biopsy monotherapy mutational load nonhuman Notch signaling overall survival pneumonia/si [Side Effect] progression free survival review *small cell lung cancer/dt [Drug Therapy] *small cell lung cancer/rt [Radiotherapy] solid malignant neoplasm/dt [Drug Therapy] adavosertib/ct [Clinical Trial] adavosertib/cb [Drug Combination] adavosertib/dt [Drug Therapy] alisertib/ct [Clinical Trial] alisertib/cb [Drug Combination] alisertib/cm [Drug Comparison] alisertib/dt [Drug Therapy] anlotinib/ae [Adverse Drug Reaction] anlotinib/ct [Clinical Trial] carboplatin/ae [Adverse Drug Reaction] carboplatin/ct [Clinical Trial] carboplatin/cb [Drug Combination] carboplatin/dt [Drug Therapy] cediranib/ct [Clinical Trial] cediranib/cb [Drug Combination] cediranib/dt [Drug Therapy] cisplatin/ct [Clinical Trial] cisplatin/cb [Drug Combination] cisplatin/dt [Drug Therapy] cixutumumab/cb [Drug Combination] cixutumumab/dt [Drug Therapy] crlx101/ct [Clinical Trial] crlx101/cb [Drug Combination] crlx101/dt [Drug Therapy] durvalumab/ct [Clinical Trial] durvalumab/cb [Drug Combination] durvalumab/dt [Drug Therapy] etoposide/ae [Adverse Drug Reaction] etoposide/ct [Clinical Trial] etoposide/cb [Drug Combination] etoposide/dt [Drug Therapy] gemcitabine/ct [Clinical Trial] gemcitabine/cb [Drug Combination] gemcitabine/dt [Drug Therapy] ipilimumab/ae [Adverse Drug Reaction] ipilimumab/ct [Clinical Trial] ipilimumab/cb [Drug Combination] ipilimumab/cm [Drug Comparison] ipilimumab/dt [Drug Therapy] lurbinectedin/ae [Adverse Drug Reaction] lurbinectedin/ct [Clinical Trial] lurbinectedin/dt [Drug Therapy] lurbinectedin/tm [Unexpected Outcome of Drug Treatment] niraparib/ct [Clinical Trial] niraparib/cb [Drug Combination] niraparib/cm [Drug Comparison] niraparib/dt [Drug Therapy] nivolumab/ae [Adverse Drug Reaction] nivolumab/ct [Clinical Trial] nivolumab/cb [Drug Combination] nivolumab/cm [Drug Comparison] nivolumab/dt [Drug Therapy] olaparib/ae [Adverse Drug Reaction] olaparib/ct [Clinical Trial] olaparib/cb [Drug Combination] olaparib/cm [Drug Comparison] olaparib/dt [Drug Therapy] paclitaxel/ct [Clinical Trial] paclitaxel/cb [Drug Combination] paclitaxel/dt [Drug Therapy] placebo prexasertib/ct [Clinical Trial] prexasertib/cb [Drug Combination] prexasertib/dt [Drug Therapy] rovalpituzumab tesirine/ct [Clinical Trial] rovalpituzumab tesirine/cb [Drug Combination] rovalpituzumab tesirine/cm [Drug Comparison] rovalpituzumab tesirine/dt [Drug Therapy] rucaparib/ct [Clinical Trial] rucaparib/cb [Drug Combination] rucaparib/dt [Drug Therapy] sonidegib/ct [Clinical Trial] sonidegib/cb [Drug Combination] sonidegib/dt [Drug Therapy] sonidegib/tm [Unexpected Outcome of Drug Treatment] taladegib/ct [Clinical Trial] taladegib/cb [Drug Combination] taladegib/dt [Drug Therapy] talazoparib/dt [Drug Therapy] talazoparib/tm [Unexpected Outcome of Drug Treatment] temozolomide/ae [Adverse Drug Reaction] temozolomide/ct [Clinical Trial] temozolomide/cb [Drug Combination] temozolomide/dt [Drug Therapy] topotecan/ct [Clinical Trial] topotecan/cm [Drug Comparison] topotecan/dt [Drug Therapy] unindexed drug veliparib/ae [Adverse Drug Reaction] veliparib/ct [Clinical Trial] veliparib/cb [Drug Combination] veliparib/cm [Drug Comparison] veliparib/dt [Drug Therapy] vismodegib/dt [Drug Therapy] vismodegib/cb [Drug Combination] anlotinib/cm [Drug Comparison] anlotinib/dt [Drug Therapy] bevacizumab/ct [Clinical Trial] bevacizumab/cb [Drug Combination] bevacizumab/dt [Drug Therapy] adoptive immunotherapy anorexia/si [Side Effect] blood toxicity/si [Side Effect] bone marrow suppression/si [Side Effect] cancer immunotherapy cancer resistance circulating tumor cell DNA damage response drug dose escalation drug potentiation encephalitis / side effect fatigue / side effect genetic heterogeneity genomics hand foot syndrome / side effect hedgehog signaling human hypertension / side effect liquid biopsy monotherapy mutational load nonhuman Notch signaling overall survival pneumonia / side effect progression free survival Review blood toxicity / side effect solid malignant neoplasm / drug therapy anorexia / side effect adoptive immunotherapy *small cell lung cancer / *drug therapy / *radiotherapy bone marrow suppression / side effect cancer immunotherapy cancer resistance circulating tumor cell DNA damage response drug dose escalation drug efficacy |
Type of Clinical Study or Trial: | Review article (e.g. literature review, narrative review) |
Appears in Collections: | Articles |
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