Learning objectives for “Quadrivalent Vaccine against Human Papillomavirus to
Prevent High-Grade Cervical Lesions:”
*Diagram the basic life cycle of a human papillomavirus, including infection, replication,
and release or integration.
*Contrast the effects of HPV16 and HPV18 on the host cell cycle that make them more
likely to cause cervical cancer than HPV6 and HPV11; describe the molecular
mechanism by which E6 and E7 proteins mediate this effect.
*Describe a general sequence of events by which HPV16 or HPV18 infection can lead to
the development of cancer.
*Describe the basic design of the study and explain why HPV6, HPV11, HPV16, and
HPV18 were used to produce the vaccine.
*List the 4 - 6 major questions addressed in the paper, and for each, briefly describe the
experiments that answered it, and state the answer to the question.
Learning objectives for “Inhibition of Poly(ADP-Ribose) Polymerase in Tumors
from BRCA Mutation Carriers:”
*Describe a sequence of events by which defects in DNA repair genes can contribute to
the development of cancer, including the role of unrepaired DNA damage contributing to
mutations.
*Define and explain “synthetic lethality,” and describe conceptually a process by which
this approach could be used to identify drugs that could target specific types of cancer.
*Name and diagram the types of DNA damage repair that can be disrupted by defects in:
1) The enzyme encoded by PARP1; and 2) The proteins encoded by BRCA1 and
BRCA2.
*Describe the sequence of molecular events by which inhibition of the PARP1 enzyme
increases the type of DNA damage that must be repaired by homologous recombination.
*List the 4-6 major questions addressed in the paper, and for each, briefly describe the
experiments that answered it, and state the answer to the question.
Learning objectives for “Pertuzumab plus Trastuzumab plus Docetaxel for
Metastatic Breast Cancer:”
*Explain why the investigators chose to target two different classes of molecules (Her2,
which is a cell-signaling/receptor molecule, and Microtubules, which are structural
molecules) to treat metastatic breast cancer.
*Describe conceptually how a combination of mutations in tumor suppressor genes,
proto-oncogenes, and other cancer susceptibility genes could contribute to the
development of cancer.
*Explain why targeting two different epitopes of a receptor molecule can be more
effective than targeting just one epitope for inactivating the receptor molecule.
*Describe the effect of taxol (a.k.a. paclitaxel) on microtubule dynamics, and explain
why this effect makes taxol a useful chemotherapeutic agent.
*List the members of the Human Epidermal Growth Factor Receptor (HER) family
*List the 4 - 6 major questions addressed in the paper, and for each, briefly describe the
experiments that answered it, and state the answer to the question.
Learning objectives for “Improved Survival with Vemurafenib in Melanoma with
BRAF V600E Mutations:”
*Explain how mutations in genes encoding components of a signaling pathway can
contribute to the development of cancer, and describe a specific example.
*Describe the structure and localization of receptor tyrosine kinases (RTKs), and explain
the signal transduction pathways by which they can regulate cell proliferation and
survival. (This Learning Objective relates to both this Literature Group paper and Dr.
Ghosh’s Cell Signaling lecture.)
*Explain the general mechanisms by which the V600E mutation in BRAF contributes to
the development of melanoma, and by which Vemurafenib can effectively treat
melanomas carrying the V600E BRAF mutation.
*Explain why overexpression of Cyclin D1 can cause resistance to Vemurafenib in a
melanoma that carries the BRAF V600E mutation.
*List the 4 - 6 major questions addressed in the paper, and for each, briefly describe the
experiments that answered it, and state the answer to the question.